{ "title": "DisMech assay and NAM inventory: issues and PRs by gingin77", "generated": "2026-10-13", "first_compiled": "2026-10-08", "repository": "https://github.com/monarch-initiative/dismech", "scope": "Issues and PRs authored, assigned or commented on by gingin77 whose focus is a method, assay, model system, NAM, or a framework for recording how a mechanism is measured. Disease curation work is excluded. Record links point at the live DisMech site; issue and PR metadata was read from GitHub on the generation date. The AOP framework groups are listed in aop-framework-inventory-2026-10-13.md; each group's document field says which file it appears in.", "counts": { "groups": 35, "issues": 33, "prs": 39 }, "groups": [ { "id": "nameRS-epic", "section": "1. Organ-chips, organoids and iPSC models from the NAMeRS symposium", "title": "Epic: curate NAMs from the NAMeRS 2026 Summit", "issues": [ 4873 ], "prs": [], "note": "Epic authored by mellybelly; gingin77 commented and split out #9792, #9793 and #9794. Child PRs were opened by repository agents and are listed under the issue, not as inventory items.", "issue_urls": [ "https://github.com/monarch-initiative/dismech/issues/4873" ], "pr_urls": [], "document": "nam-methods-inventory-2026-10-13.md" }, { "id": "nsclc-organ-chip", "section": "1. Organ-chips, organoids and iPSC models from the NAMeRS symposium", "title": "NSCLC lung organ-chip as a structured experimental model", "issues": [ 9792 ], "prs": [ 9931, 9665 ], "issue_urls": [ "https://github.com/monarch-initiative/dismech/issues/9792" ], "pr_urls": [ "https://github.com/monarch-initiative/dismech/pull/9931", "https://github.com/monarch-initiative/dismech/pull/9665" ], "document": "nam-methods-inventory-2026-10-13.md" }, { "id": "escc-organoid", "section": "1. Organ-chips, organoids and iPSC models from the NAMeRS symposium", "title": "Esophageal squamous cell carcinoma patient-derived organoid", "issues": [ 9793 ], "prs": [ 9797 ], "issue_urls": [ "https://github.com/monarch-initiative/dismech/issues/9793" ], "pr_urls": [ "https://github.com/monarch-initiative/dismech/pull/9797" ], "document": "nam-methods-inventory-2026-10-13.md" }, { "id": "computational-nam-scope", "section": "1. Organ-chips, organoids and iPSC models from the NAMeRS symposium", "title": "Scope decision for purely computational NAM evidence", "issues": [ 9794 ], "prs": [], "issue_urls": [ "https://github.com/monarch-initiative/dismech/issues/9794" ], "pr_urls": [], "document": "nam-methods-inventory-2026-10-13.md" }, { "id": "namo-seven-models", "section": "2. The NAMO rare-disease model bridge", "title": "Seven NAM models never reach the pathograph", "issues": [ 10432 ], "prs": [ 10573, 10430 ], "issue_urls": [ "https://github.com/monarch-initiative/dismech/issues/10432" ], "pr_urls": [ "https://github.com/monarch-initiative/dismech/pull/10573", "https://github.com/monarch-initiative/dismech/pull/10430" ], "document": "nam-methods-inventory-2026-10-13.md" }, { "id": "nam-target-diseases", "section": "2. The NAMO rare-disease model bridge", "title": "Tracking high-value NAM target diseases", "issues": [ 802, 10822 ], "prs": [ 12582 ], "issue_urls": [ "https://github.com/monarch-initiative/dismech/issues/802", "https://github.com/monarch-initiative/dismech/issues/10822" ], "pr_urls": [ "https://github.com/monarch-initiative/dismech/pull/12582" ], "document": "nam-methods-inventory-2026-10-13.md" }, { "id": "liver-fibrosis-mps", "section": "3. Liver fibrosis MPS and the fibrotic_response module", "title": "First liver fibrosis NAM on Liver_Cirrhosis and the DILI module", "issues": [], "prs": [ 9935 ], "issue_urls": [], "pr_urls": [ "https://github.com/monarch-initiative/dismech/pull/9935" ], "document": "nam-methods-inventory-2026-10-13.md" }, { "id": "fibrotic-response-models", "section": "3. Liver fibrosis MPS and the fibrotic_response module", "title": "Experimental models for the fibrotic_response module", "issues": [ 9997 ], "prs": [ 10282 ], "issue_urls": [ "https://github.com/monarch-initiative/dismech/issues/9997" ], "pr_urls": [ "https://github.com/monarch-initiative/dismech/pull/10282" ], "document": "nam-methods-inventory-2026-10-13.md" }, { "id": "aop38-bridge-test", "section": "3. Liver fibrosis MPS and the fibrotic_response module", "title": "Liver fibrosis NAM as the test case for the AOP Assay/NAM bridge", "issues": [ 10051 ], "prs": [ 10257, 10299 ], "issue_urls": [ "https://github.com/monarch-initiative/dismech/issues/10051" ], "pr_urls": [ "https://github.com/monarch-initiative/dismech/pull/10257", "https://github.com/monarch-initiative/dismech/pull/10299" ], "document": "nam-methods-inventory-2026-10-13.md" }, { "id": "aop-emod-alignment", "section": "1. AOP and EMOD framework alignment", "title": "Explore how exposure modelling relates to the AOP framework", "issues": [ 8309 ], "prs": [ 10002 ], "issue_urls": [ "https://github.com/monarch-initiative/dismech/issues/8309" ], "pr_urls": [ "https://github.com/monarch-initiative/dismech/pull/10002" ], "document": "data/aop-framework-inventory-2026-10-13.md" }, { "id": "aop-not-a-boundary", "section": "1. AOP and EMOD framework alignment", "title": "Comparator change and 'an AOP is not a mechanism boundary'", "issues": [ 10344, 10687 ], "prs": [ 10760 ], "issue_urls": [ "https://github.com/monarch-initiative/dismech/issues/10344", "https://github.com/monarch-initiative/dismech/issues/10687" ], "pr_urls": [ "https://github.com/monarch-initiative/dismech/pull/10760" ], "document": "data/aop-framework-inventory-2026-10-13.md" }, { "id": "how-a-claim-was-measured", "section": "1. AOP and EMOD framework alignment", "title": "Evidence cannot record how a causal claim was measured", "issues": [ 10772 ], "prs": [ 11394 ], "issue_urls": [ "https://github.com/monarch-initiative/dismech/issues/10772" ], "pr_urls": [ "https://github.com/monarch-initiative/dismech/pull/11394" ], "document": "data/aop-framework-inventory-2026-10-13.md" }, { "id": "aop-schema-questions", "section": "1. AOP and EMOD framework alignment", "title": "Six open AOP schema questions", "issues": [ 10272 ], "prs": [], "issue_urls": [ "https://github.com/monarch-initiative/dismech/issues/10272" ], "pr_urls": [], "document": "data/aop-framework-inventory-2026-10-13.md" }, { "id": "aop-use-cases-and-errors", "section": "1. AOP and EMOD framework alignment", "title": "AOP-derived causal evidence use cases and AOP-Wiki data error inventory", "issues": [ 10454, 10773 ], "prs": [], "issue_urls": [ "https://github.com/monarch-initiative/dismech/issues/10454", "https://github.com/monarch-initiative/dismech/issues/10773" ], "pr_urls": [], "document": "data/aop-framework-inventory-2026-10-13.md" }, { "id": "aop-skills", "section": "1. AOP and EMOD framework alignment", "title": "AOP-Wiki and MIE-KER-capture skills", "issues": [ 10456 ], "prs": [ 10464 ], "issue_urls": [ "https://github.com/monarch-initiative/dismech/issues/10456" ], "pr_urls": [ "https://github.com/monarch-initiative/dismech/pull/10464" ], "document": "data/aop-framework-inventory-2026-10-13.md" }, { "id": "seed-aops-from-dismech", "section": "2. Seeding AOPs from dismech, and edge confidence", "title": "Which dismech pathographs could seed Adverse Outcome Pathways", "issues": [], "prs": [ 11852 ], "issue_urls": [], "pr_urls": [ "https://github.com/monarch-initiative/dismech/pull/11852" ], "document": "data/aop-framework-inventory-2026-10-13.md" }, { "id": "edge-confidence", "section": "2. Seeding AOPs from dismech, and edge confidence", "title": "A causal edge cannot carry a confidence", "issues": [ 10949 ], "prs": [], "issue_urls": [ "https://github.com/monarch-initiative/dismech/issues/10949" ], "pr_urls": [], "document": "data/aop-framework-inventory-2026-10-13.md" }, { "id": "tdar-aop", "section": "4. The T-cell dependent antibody response (TDAR) assay", "title": "TDAR AOP project page, accounting correction, failed claims and actions", "issues": [], "prs": [ 11857, 11905, 12003 ], "issue_urls": [], "pr_urls": [ "https://github.com/monarch-initiative/dismech/pull/11857", "https://github.com/monarch-initiative/dismech/pull/11905", "https://github.com/monarch-initiative/dismech/pull/12003" ], "document": "nam-methods-inventory-2026-10-13.md" }, { "id": "toxcast-structured-source", "section": "5. ToxCast and Tox21 assay endpoints", "title": "ToxCast as a structured reference source", "issues": [ 12682 ], "prs": [], "issue_urls": [ "https://github.com/monarch-initiative/dismech/issues/12682" ], "pr_urls": [], "document": "nam-methods-inventory-2026-10-13.md" }, { "id": "toxcast-assay-mapping", "section": "5. ToxCast and Tox21 assay endpoints", "title": "Map ToxCast assays to pathograph nodes using assay metadata", "issues": [ 12858 ], "prs": [ 12923, 13226, 13228, 13236 ], "issue_urls": [ "https://github.com/monarch-initiative/dismech/issues/12858" ], "pr_urls": [ "https://github.com/monarch-initiative/dismech/pull/12923", "https://github.com/monarch-initiative/dismech/pull/13226", "https://github.com/monarch-initiative/dismech/pull/13228", "https://github.com/monarch-initiative/dismech/pull/13236" ], "document": "nam-methods-inventory-2026-10-13.md" }, { "id": "toxcast-go-bridges", "section": "5. ToxCast and Tox21 assay endpoints", "title": "GO-resolving biologicalProcessTarget values and mitochondrial depolarization bridge", "issues": [ 13224, 13225 ], "prs": [], "issue_urls": [ "https://github.com/monarch-initiative/dismech/issues/13224", "https://github.com/monarch-initiative/dismech/issues/13225" ], "pr_urls": [], "document": "nam-methods-inventory-2026-10-13.md" }, { "id": "edsp-history", "section": "5. ToxCast and Tox21 assay endpoints", "title": "Endocrine Disruptor Screening Program history", "issues": [ 13161 ], "prs": [ 13219 ], "issue_urls": [ "https://github.com/monarch-initiative/dismech/issues/13161" ], "pr_urls": [ "https://github.com/monarch-initiative/dismech/pull/13219" ], "document": "nam-methods-inventory-2026-10-13.md" }, { "id": "dnt-ivb-coverage", "section": "6. Developmental neurotoxicity batteries and the zebrafish VAMR assay", "title": "DNT in vitro battery coverage of the pathograph", "issues": [], "prs": [ 13424 ], "issue_urls": [], "pr_urls": [ "https://github.com/monarch-initiative/dismech/pull/13424" ], "document": "nam-methods-inventory-2026-10-13.md" }, { "id": "zebrafish-vamr", "section": "6. Developmental neurotoxicity batteries and the zebrafish VAMR assay", "title": "Zebrafish visual and acoustic motor response (VAMR) assay", "issues": [ 13450 ], "prs": [ 13451, 13452, 13463 ], "issue_urls": [ "https://github.com/monarch-initiative/dismech/issues/13450" ], "pr_urls": [ "https://github.com/monarch-initiative/dismech/pull/13451", "https://github.com/monarch-initiative/dismech/pull/13452", "https://github.com/monarch-initiative/dismech/pull/13463" ], "document": "nam-methods-inventory-2026-10-13.md" }, { "id": "celegans-mdd-models", "section": "7. Caenorhabditis elegans models for Major Depressive Disorder", "title": "Seed MDD animal models from C. elegans serotonin, insulin/FOXO and antidepressant pharmacology", "issues": [ 13749 ], "prs": [ 13755, 13756, 13757, 13759, 13776 ], "issue_urls": [ "https://github.com/monarch-initiative/dismech/issues/13749" ], "pr_urls": [ "https://github.com/monarch-initiative/dismech/pull/13755", "https://github.com/monarch-initiative/dismech/pull/13756", "https://github.com/monarch-initiative/dismech/pull/13757", "https://github.com/monarch-initiative/dismech/pull/13759", "https://github.com/monarch-initiative/dismech/pull/13776" ], "document": "nam-methods-inventory-2026-10-13.md" }, { "id": "mood-disorders-no-models", "section": "7. Caenorhabditis elegans models for Major Depressive Disorder", "title": "Mood disorders record no models at all", "issues": [ 13754 ], "prs": [], "issue_urls": [ "https://github.com/monarch-initiative/dismech/issues/13754" ], "pr_urls": [], "document": "nam-methods-inventory-2026-10-13.md" }, { "id": "nam-scope", "section": "8. NAM scope, the lithium models, and the valproate and lithium report", "title": "NAMs inventory: what fits and what is fringe", "issues": [ 13602 ], "prs": [], "issue_urls": [ "https://github.com/monarch-initiative/dismech/issues/13602" ], "pr_urls": [], "document": "nam-methods-inventory-2026-10-13.md" }, { "id": "lithium-npc-model", "section": "8. NAM scope, the lithium models, and the valproate and lithium report", "title": "Bipolar Disorder lithium-exposed neural progenitor and patient iPSC neuron models", "issues": [ 13600 ], "prs": [ 13788, 13603 ], "issue_urls": [ "https://github.com/monarch-initiative/dismech/issues/13600" ], "pr_urls": [ "https://github.com/monarch-initiative/dismech/pull/13788", "https://github.com/monarch-initiative/dismech/pull/13603" ], "document": "nam-methods-inventory-2026-10-13.md" }, { "id": "vpa-lithium-gxt-report", "section": "8. NAM scope, the lithium models, and the valproate and lithium report", "title": "Valproic acid and lithium gene-by-treatment report", "issues": [], "prs": [ 13787, 13794 ], "issue_urls": [], "pr_urls": [ "https://github.com/monarch-initiative/dismech/pull/13787", "https://github.com/monarch-initiative/dismech/pull/13794" ], "document": "nam-methods-inventory-2026-10-13.md" }, { "id": "animal-model-organism-perturbation", "section": "9. Model organism, gene namespace and perturbation schema", "title": "AnimalModel cannot bind its organism or record a non-genetic perturbation", "issues": [ 13768, 13774 ], "prs": [], "issue_urls": [ "https://github.com/monarch-initiative/dismech/issues/13768", "https://github.com/monarch-initiative/dismech/issues/13774" ], "pr_urls": [], "document": "nam-methods-inventory-2026-10-13.md" }, { "id": "model-gene-namespaces", "section": "9. Model organism, gene namespace and perturbation schema", "title": "Non-human gene identifiers on model genes", "issues": [ 11140 ], "prs": [ 13548 ], "issue_urls": [ "https://github.com/monarch-initiative/dismech/issues/11140" ], "pr_urls": [ "https://github.com/monarch-initiative/dismech/pull/13548" ], "document": "nam-methods-inventory-2026-10-13.md" }, { "id": "bgee-fidelity", "section": "10. Model fidelity and readout grading", "title": "Bgee cross-species model fidelity check", "issues": [], "prs": [ 10513 ], "issue_urls": [], "pr_urls": [ "https://github.com/monarch-initiative/dismech/pull/10513" ], "document": "nam-methods-inventory-2026-10-13.md" }, { "id": "ganab-readout-grading", "section": "10. Model fidelity and readout grading", "title": "Inverted readout grading on the Ganab mouse", "issues": [], "prs": [ 10350 ], "issue_urls": [], "pr_urls": [ "https://github.com/monarch-initiative/dismech/pull/10350" ], "document": "nam-methods-inventory-2026-10-13.md" }, { "id": "phenotype-readout", "section": "10. Model fidelity and readout grading", "title": "A phenotype as the readout of a mechanism", "issues": [ 11427 ], "prs": [], "issue_urls": [ "https://github.com/monarch-initiative/dismech/issues/11427" ], "pr_urls": [], "document": "nam-methods-inventory-2026-10-13.md" }, { "id": "evidence-strength-assay-typing", "section": "10. Model fidelity and readout grading", "title": "Evidence strength, study design and assay typing", "issues": [ 9421 ], "prs": [], "issue_urls": [ "https://github.com/monarch-initiative/dismech/issues/9421" ], "pr_urls": [], "document": "nam-methods-inventory-2026-10-13.md" } ], "issues": { "4873": { "number": 4873, "type": "issue", "title": "curate NAMs from NAMsters symposium", "url": "https://github.com/monarch-initiative/dismech/issues/4873", "state": "open", "author": "mellybelly", "created": "2026-06-27", "closed": null, "assignees": [], "labels": [ "enhancement", "curation", "high_effort", "claim" ], "gingin77_role": "commented", "group": "nameRS-epic", "why": "Enrich existing entries with NAM evidence from presenters at the Triangle CERSI NAMeRS 2026 summit (organoids, organ-chips, iPSC, zebrafish, in silico).", "achieved": "Agent-authored child PRs (#4874, #4892, #4910, #4940, #4972, #5004, #5336, #5477, #7123, #8886) added the platforms listed under methods to nine entries and modules, mostly as evidence items and later as structured experimental_models.", "blockers": "Two Griffith PMIDs in the auto-summary were hallucinated and several agent-recalled PMIDs resolved to the wrong paper. The EAC chip modelled a docetaxel triplet, not the CROSS regimen. just validate-references reported zero checks on modules. The scanner re-audited the whole epic until gingin77 split out #9792, #9793 and #9794. Virtual imaging trials, tonsil explants and tumour-on-chip immunotherapy were never curated.", "methods": [ "Griffith droplet-microfluidic protease activity (PrAMA) platform", "Wyss lung organ-chip", "zebrafish novel-tank, dark-flash thigmotaxis and edge-preference anxiety assays", "iPSC liver organoid / liver-on-chip", "stroma-inclusive EAC organ-chip", "vascularized bone-marrow-on-chip", "TNNT2 R173W iPSC-cardiomyocytes", "iPSC sensory-neuron microphysiological system with deep-learning readout", "Liver-Chip, iPSC liver organoids, HLA-genotyped organoid plus CD8 T-cell co-culture" ], "dismech_records": [ { "name": "Endometriosis", "url": "https://dismech.monarchinitiative.org/pages/disorders/Endometriosis.html" }, { "name": "Non-Small_Cell_Lung_Cancer", "url": "https://dismech.monarchinitiative.org/pages/disorders/Non-Small_Cell_Lung_Cancer.html" }, { "name": "Generalized_Anxiety_Disorder", "url": "https://dismech.monarchinitiative.org/pages/disorders/Generalized_Anxiety_Disorder.html" }, { "name": "Acetaminophen_Hepatotoxicity", "url": "https://dismech.monarchinitiative.org/pages/disorders/Acetaminophen_Hepatotoxicity.html" }, { "name": "Esophageal_Adenocarcinoma", "url": "https://dismech.monarchinitiative.org/pages/disorders/Esophageal_Adenocarcinoma.html" }, { "name": "Chemotherapy_Induced_Neutropenia", "url": "https://dismech.monarchinitiative.org/pages/disorders/Chemotherapy-Induced_Neutropenia.html" }, { "name": "Dilated_Cardiomyopathy", "url": "https://dismech.monarchinitiative.org/pages/disorders/Dilated_Cardiomyopathy.html" }, { "name": "peripheral_axonal_degeneration", "url": "https://dismech.monarchinitiative.org/pages/modules/peripheral_axonal_degeneration.html" }, { "name": "drug_induced_liver_injury", "url": "https://dismech.monarchinitiative.org/pages/modules/drug_induced_liver_injury.html" } ], "agent_authored_child_prs": [ "https://github.com/monarch-initiative/dismech/pull/4874", "https://github.com/monarch-initiative/dismech/pull/4892", "https://github.com/monarch-initiative/dismech/pull/4910", "https://github.com/monarch-initiative/dismech/pull/4940", "https://github.com/monarch-initiative/dismech/pull/4972", "https://github.com/monarch-initiative/dismech/pull/5004", "https://github.com/monarch-initiative/dismech/pull/5336", "https://github.com/monarch-initiative/dismech/pull/5477", "https://github.com/monarch-initiative/dismech/pull/7123", "https://github.com/monarch-initiative/dismech/pull/8886" ] }, "9792": { "number": 9792, "type": "issue", "title": "Link the NSCLC lung organ-chip into the pathograph as a structured experimental_models entry", "url": "https://github.com/monarch-initiative/dismech/issues/9792", "state": "closed", "author": "gingin77", "created": "2026-08-28", "closed": "2026-08-29", "assignees": [ "gingin77" ], "labels": [ "enhancement", "curation", "medium_effort" ], "gingin77_role": "author", "group": "nsclc-organ-chip", "why": "The lung organ-chip paper was cited only as an evidence item on the Targeted Therapy treatment; with no experimental_models record the model was invisible to the mechanism graph.", "achieved": "PR #9665 (mellybelly) added the ORGAN_ON_CHIP record with links to Oncogenic Driver Mutations, Tumor Microenvironment Remodeling and Metastasis; #9931 then grounded the TKI readout in GO and closed this issue.", "blockers": "Paper cache is abstract-only (publisher returns 403), so quotable text was nearly exhausted. gingin77 objected that the Tumor Microenvironment link overclaims because the chip has no immune or stromal cells, and that cell_types and cell_source are not in the cached abstract. The dormancy/persister finding has no home node. The structured fidelity, limitations and readouts layer of ModelMechanismLink is essentially unused for NAMs.", "methods": [ "human orthotopic NSCLC lung organ-chip (Hassell 2017, PMID:29020635)" ], "dismech_records": [ { "name": "Non-Small_Cell_Lung_Cancer", "url": "https://dismech.monarchinitiative.org/pages/disorders/Non-Small_Cell_Lung_Cancer.html" } ] }, "9793": { "number": 9793, "type": "issue", "title": "Esophageal squamous cell carcinoma has no NAM (organoid/organ-chip) evidence", "url": "https://github.com/monarch-initiative/dismech/issues/9793", "state": "closed", "author": "gingin77", "created": "2026-08-28", "closed": "2026-08-28", "assignees": [ "gingin77" ], "labels": [ "enhancement", "curation", "medium_effort" ], "gingin77_role": "author", "group": "escc-organoid", "why": "ESCC had no organoid, chip or iPSC evidence; its only in vitro item was a conventional SOX2 cell-line study while the adenocarcinoma sibling got a tumour-chip citation.", "achieved": "Resolved by PR #9797.", "blockers": "No ESCC organ-chip literature exists, so the entry got an organoid NAM instead. A batched Europe PMC query returned the wrong abstract under one PMID, so each PMID had to be fetched individually. Two candidates were rejected: murine organoids with an allograft readout, and an editorial.", "methods": [ "ESCC patient-derived organoid library (Nakagawa 2025, PMID:40169778)" ], "dismech_records": [ { "name": "Esophageal_Squamous_Cell_Carcinoma", "url": "https://dismech.monarchinitiative.org/pages/disorders/Esophageal_Squamous_Cell_Carcinoma.html" } ] }, "9794": { "number": 9794, "type": "issue", "title": "Scope decision: where does purely computational NAM evidence (virtual imaging trials) belong?", "url": "https://github.com/monarch-initiative/dismech/issues/9794", "state": "open", "author": "gingin77", "created": "2026-08-28", "closed": null, "assignees": [ "cmungall" ], "labels": [ "enhancement", "help wanted", "question", "high_effort", "discussion" ], "gingin77_role": "author", "group": "computational-nam-scope", "why": "The in-silico strand of NAMeRS was never curated and no cardiovascular entry is an obvious home; it needs a maintainer decision, not a curation run.", "achieved": "Nothing added; no maintainer decision recorded.", "blockers": "The bot argued the design decisions already exclude acquisition parameters, per-patient reads and radiology decision support, which a virtual imaging trial simulates, and that Sauer 2024 makes no claim about how atherosclerosis works. Proposed criterion: judge by what the paper claims, not the method. COMPUTATIONAL evidence is thin (642 items vs 9,065 IN_VITRO).", "methods": [ "virtual imaging trials (Duke Center for Virtual Imaging Trials)", "atrial fibrillation in-silico trials (suggested alternative)" ], "dismech_records": [] }, "10432": { "number": 10432, "type": "issue", "title": "Seven NAM experimental models in Stargardt, Noonan, and Ulcerative Colitis never reach the pathograph", "url": "https://github.com/monarch-initiative/dismech/issues/10432", "state": "closed", "author": "gingin77", "created": "2026-09-01", "closed": "2026-09-05", "assignees": [], "labels": [ "enhancement", "curation", "medium_effort" ], "gingin77_role": "author", "group": "namo-seven-models", "why": "Thirteen non-animal models were curated for the NAMO rare-disease bridge, but the seven in Stargardt, Noonan and Ulcerative Colitis had no modeled_mechanisms and sat as disconnected list entries.", "achieved": "Fixed by agent PR #10573, which wired each model to pathograph nodes with typed relationships.", "blockers": "The issue's candidate targets were wrong in three places (the retinal organoid paper supports no RPE, lipofuscin or A2E link). A RAF1 S257L paper contradicts the ERK to hypertrophy edge and was recorded as REFUTE with HUMAN_MODEL_MISMATCH. The healthy-tissue colon-on-chip was capped at MEASURES/LOW. No coverage metric exists for model-to-mechanism wiring. CF and Crohn's links still lack relationship, fidelity and limitations.", "methods": [ "retinal organoid", "iPSC-RPE", "cortical organoid", "iPSC-cardiomyocytes", "air-liquid-interface colonoid", "cytokine-conditioned hiPSC colon organoid", "colon-on-chip" ], "dismech_records": [ { "name": "Stargardt_Disease", "url": "https://dismech.monarchinitiative.org/pages/disorders/Stargardt_Disease.html" }, { "name": "Noonan_Syndrome", "url": "https://dismech.monarchinitiative.org/pages/disorders/Noonan_Syndrome.html" }, { "name": "Ulcerative_Colitis", "url": "https://dismech.monarchinitiative.org/pages/disorders/Ulcerative_Colitis.html" } ] }, "802": { "number": 802, "type": "issue", "title": "Track missing high-value NAM target diseases for future dismech entries", "url": "https://github.com/monarch-initiative/dismech/issues/802", "state": "open", "author": "cmungall", "created": "2026-03-31", "closed": null, "assignees": [], "labels": [ "enhancement" ], "gingin77_role": "commented (authored by cmungall)", "group": "nam-target-diseases", "why": "Parking lot for diseases absent from dismech with strong organoid/MPS literature, so models can be linked to pathograph nodes rather than free text.", "achieved": "gingin77's 2026-09-23 status: all seven diseases now have entries; reframed as a NAM-linkage checklist. After #12582 only Usher remains open. IPF was already done (lung-on-chip and AT2/fibroblast organoid, conforming to fibrotic_response).", "blockers": "Usher waits on node structure from #10822. No parent-level CRC, RP or LCA entries by the granularity decision. Auto-summary MONDO IDs were wrong and corrected. No RPE65/LCA2 entry yet.", "methods": [ "organoid and MPS literature for CRC, TSC, RP, IPF, LCA, Usher and Wilson disease" ], "dismech_records": [ { "name": "BBSome-Related_Retinitis_Pigmentosa", "url": "https://dismech.monarchinitiative.org/pages/disorders/BBSome-related_retinitis_pigmentosa.html" }, { "name": "Wilsons_Disease", "url": "https://dismech.monarchinitiative.org/pages/disorders/Wilson_Disease.html" }, { "name": "Leber_Congenital_Amaurosis_10", "url": "https://dismech.monarchinitiative.org/pages/disorders/Leber_Congenital_Amaurosis_10.html" }, { "name": "Tuberous_Sclerosis_Complex", "url": "https://dismech.monarchinitiative.org/pages/disorders/Tuberous_Sclerosis_Complex.html" }, { "name": "BRAF_V600E_Mutant_Colorectal_Cancer", "url": "https://dismech.monarchinitiative.org/pages/disorders/BRAF_V600E-Mutant_Colorectal_Cancer.html" }, { "name": "MSI_High_Colorectal_Cancer", "url": "https://dismech.monarchinitiative.org/pages/disorders/MSI-High_Colorectal_Cancer.html" } ] }, "10822": { "number": 10822, "type": "issue", "title": "Lump/split: Usher syndrome models one protein complex that does not exist — split into four mechanism entities plus a grouping", "url": "https://github.com/monarch-initiative/dismech/issues/10822", "state": "closed", "author": "cmungall", "created": "2026-09-04", "closed": "2026-09-25", "assignees": [], "labels": [ "schema", "curation", "discussion", "decision", "lump-split decision", "very-hard" ], "gingin77_role": "referenced", "group": "nam-target-diseases", "why": "Usher syndrome node structure that the NAM-linkage checklist in #802 depends on.", "achieved": "Not part of this inventory; referenced as the blocker for the Usher row.", "blockers": "Open at compile time.", "methods": [], "dismech_records": [] }, "9997": { "number": 9997, "type": "issue", "title": "Add experimental models to the fibrotic_response module", "url": "https://github.com/monarch-initiative/dismech/issues/9997", "state": "closed", "author": "gingin77", "created": "2026-08-29", "closed": "2026-08-31", "assignees": [], "labels": [ "enhancement", "curation", "high_effort" ], "gingin77_role": "author", "group": "fibrotic-response-models", "why": "fibrotic_response is the most-reused module in the KB and carried no experimental models, a gap made visible by two newly curated organ-specific fibrosis NAMs that both land on its nodes.", "achieved": "Asked for an experimental_models block on the module linked to Mesenchymal Cell Activation and Excessive ECM Deposition; delivered by #10282.", "blockers": "The two NAMs in hand are explicitly organ-specific and neither is a fair stand-in for fibrosis generally; the entire chip and organoid fibrosis literature is organ-partitioned. Precision-cut slices were rejected as murine with no NAMO class for ex vivo slices. Module model blocks all carry tissue_term and an organ-agnostic model has nothing to put there.", "methods": [ "Scar-in-a-Jar macromolecular crowding fibroblast assay", "murine precision-cut tissue slices (rejected)" ], "dismech_records": [ { "name": "fibrotic_response", "url": "https://dismech.monarchinitiative.org/pages/modules/fibrotic_response.html" } ] }, "10051": { "number": 10051, "type": "issue", "title": "Liver fibrosis NAM as a test case for the AOP Assay/NAM bridge", "url": "https://github.com/monarch-initiative/dismech/issues/10051", "state": "closed", "author": "gingin77", "created": "2026-08-29", "closed": "2026-08-31", "assignees": [ "gingin77" ], "labels": [ "documentation", "schema", "discussion" ], "gingin77_role": "author", "group": "aop38-bridge-test", "why": "The alignment page listed Assay/NAM to ExperimentalModel as the cheapest existing bridge to AOP-Wiki and nothing had exercised it; the #9935 liver NAM is a case that can, approached assay-first rather than stressor-first.", "achieved": "A mapping proposal: KE 55 to Hepatocyte Injury and Death, KE 1492/1493 to Kupffer Cell and Inflammatory Response, KE 265 to Hepatic Stellate Cell Activation, KE 68 to Excessive ECM Deposition; MIE KE 244 unmapped. Closed by #10257.", "blockers": "Nothing in the schema refers to an AOP, KER or KE and AOP-Wiki is not citable as evidence. AOP ontology terms are leads, not bindings. Acetaminophen to KE 244 unresolved on a subscription-only paper. Both endpoints fall outside the node layer. The bot argued the mapping belongs at the module layer.", "methods": [ "AOP 38 (protein alkylation leading to liver fibrosis) mapped onto the Akura Twin MPS" ], "dismech_records": [ { "name": "Liver_Cirrhosis", "url": "https://dismech.monarchinitiative.org/pages/disorders/Liver_Cirrhosis.html" }, { "name": "fibrotic_response", "url": "https://dismech.monarchinitiative.org/pages/modules/fibrotic_response.html" }, { "name": "AOP_EMOD_ALIGNMENT", "url": "https://dismech.monarchinitiative.org/pages/projects/AOP_EMOD_ALIGNMENT.html" } ] }, "8309": { "number": 8309, "type": "issue", "title": "Explore how dismech's environmental-exposure modeling relates to the Adverse Outcome Pathway (AOP) framework", "url": "https://github.com/monarch-initiative/dismech/issues/8309", "state": "closed", "author": "gingin77", "created": "2026-08-10", "closed": "2026-09-01", "assignees": [ "caufieldjh", "gingin77" ], "labels": [ "schema", "discussion" ], "gingin77_role": "author", "group": "aop-emod-alignment", "why": "Map where dismech's exposure to mechanism to outcome layer aligns with MIE, KE, KER and AO and decide what, if anything, to adopt; pilot AOP 17 vs Lead_Poisoning.", "achieved": "Produced the AOP_EMOD_ALIGNMENT project page (#10002), the lead use case against eight lead AOPs, the AOP 38 worked example (#10257, #10299), three causal edges in Lead_Poisoning (#8392), and eight biological_scale tags.", "blockers": "Pilot premise was wrong (no mitochondria to oxidative stress edge; zero nodes with biological_scale). A weight-of-evidence grade is not evidence. The MIE/KE/AO role tag was deferred with no issue; two questions documented without a verdict.", "methods": [ "EMOD Assay, Observation and KER Evidence classes as the measurement side of the comparison" ], "dismech_records": [ { "name": "Lead_Poisoning", "url": "https://dismech.monarchinitiative.org/pages/disorders/Lead_Poisoning.html" }, { "name": "AOP_EMOD_ALIGNMENT", "url": "https://dismech.monarchinitiative.org/pages/projects/AOP_EMOD_ALIGNMENT.html" } ] }, "10344": { "number": 10344, "type": "issue", "title": "AOP/EMOD project page: record why the pilot comparator changed and clear the stale TODO", "url": "https://github.com/monarch-initiative/dismech/issues/10344", "state": "closed", "author": "gingin77", "created": "2026-09-01", "closed": "2026-09-05", "assignees": [], "labels": [ "documentation", "low-priority", "technical-debt", "low_effort" ], "gingin77_role": "author", "group": "aop-not-a-boundary", "why": "The page mapped eight lead AOPs instead of #8309's AOP 17 with the reason hidden in a non-rendering HTML comment, and carried a stale TODO.", "achieved": "Three prose edits delivered by #10760, including the ADME correction: lead absorption and distribution are toxicokinetic and ALAD inhibition is the MIE-shaped node.", "blockers": "All ten environmental entries TRIGGERS into a toxicokinetic node, so the assumed MIE correspondence is wrong in a specific direction; none of the 35 tabulated KEs is a heme or ALAD event.", "methods": [], "dismech_records": [ { "name": "Lead_Poisoning", "url": "https://dismech.monarchinitiative.org/pages/disorders/Lead_Poisoning.html" }, { "name": "AOP_EMOD_ALIGNMENT", "url": "https://dismech.monarchinitiative.org/pages/projects/AOP_EMOD_ALIGNMENT.html" } ] }, "10687": { "number": 10687, "type": "issue", "title": "Record in AOP_EMOD_ALIGNMENT that an AOP is not a mechanism boundary", "url": "https://github.com/monarch-initiative/dismech/issues/10687", "state": "open", "author": "gingin77", "created": "2026-09-03", "closed": null, "assignees": [], "labels": [ "documentation", "low-priority", "low_effort" ], "gingin77_role": "author", "group": "aop-not-a-boundary", "why": "A KER lookup on five androgen-receptor-axis KEs returned 28 KERs in two biological groups, but grouping by parent AOP scattered the 24-edge androgen group across 19 AOPs with KER 2124 in ten.", "achieved": "Partially delivered by #10760 (divergence row, three rules, Villeneuve 2014 citation); the same guidance sits in mie-ker-capture step 6.", "blockers": "Measurements, hub-KE caveat, Knapen 2018 and the networkFinder pointer were withdrawn pending a 3-vs-2 component discrepancy; the OpenScientist report still asserts three components.", "methods": [ "AOP network connected-components analysis", "AOP-networkFinder (withdrawn)" ], "dismech_records": [ { "name": "AOP_EMOD_ALIGNMENT", "url": "https://dismech.monarchinitiative.org/pages/projects/AOP_EMOD_ALIGNMENT.html" } ] }, "10772": { "number": 10772, "type": "issue", "title": "AOP_EMOD_ALIGNMENT: dismech evidence cannot record how a causal claim was measured", "url": "https://github.com/monarch-initiative/dismech/issues/10772", "state": "closed", "author": "gingin77", "created": "2026-09-03", "closed": "2026-09-08", "assignees": [ "gingin77" ], "labels": [ "documentation", "schema", "low-priority", "low_effort" ], "gingin77_role": "author", "group": "how-a-claim-was-measured", "why": "EvidenceItem can say the study category but not the experimental system or method; EMOD structures this explicitly.", "achieved": "Comparison written to the page by #11394.", "blockers": "assays already exists on Pathophysiology and Biochemical but is unused: curators were told not to use it and OBI has no OAK adapter or enum cache; ECO is absent entirely. No schema change proposed; workaround is a 'Measured by in ' prefix in explanation.", "methods": [ "whole-cell voltage clamp in isolated rabbit sino-atrial node myocytes", "FRET cAMP biosensor", "EMOD Assay.detection_technology" ], "dismech_records": [ { "name": "AOP_EMOD_ALIGNMENT", "url": "https://dismech.monarchinitiative.org/pages/projects/AOP_EMOD_ALIGNMENT.html" } ] }, "10272": { "number": 10272, "type": "issue", "title": "Work the six open AOP schema questions in the AOP/EMOD alignment project", "url": "https://github.com/monarch-initiative/dismech/issues/10272", "state": "open", "author": "gingin77", "created": "2026-08-31", "closed": null, "assignees": [ "gingin77" ], "labels": [ "documentation", "schema", "low-priority", "discussion" ], "gingin77_role": "author", "group": "aop-schema-questions", "why": "Alignment surfaced six things the schema cannot express: KE cross-reference on a node, where an AO correspondence attaches, declaring aop prefixes, a population level in BiologicalScaleEnum, species applicability on a mechanism, marking a node toxicokinetic.", "achieved": "Nothing merged; gingin77 noted it was created from a misunderstanding but kept it open for discussion. No schema change should be made on this issue alone.", "blockers": "Prefix question near-settled by namo:/clinvar: precedent; Q4 should be a recorded no (7,731 scale tags, none population-level); Q5 blocked because AnimalModel.species is free text; Q6 belongs to the aggregate exposure pathway framework; Q2 blocked on Liver_Cirrhosis having no fibrosis node (#10310).", "methods": [], "dismech_records": [ { "name": "AOP_EMOD_ALIGNMENT", "url": "https://dismech.monarchinitiative.org/pages/projects/AOP_EMOD_ALIGNMENT.html" } ] }, "10454": { "number": 10454, "type": "issue", "title": "New project: AOP-derived_causal_evidence_use_cases", "url": "https://github.com/monarch-initiative/dismech/issues/10454", "state": "open", "author": "gingin77", "created": "2026-09-01", "closed": null, "assignees": [ "gingin77" ], "labels": [ "documentation", "enhancement", "high_effort", "evidence" ], "gingin77_role": "author", "group": "aop-use-cases-and-errors", "why": "KER3445 (PDE inhibition to increased cAMP, AOP 558) checked against primary literature is false in the healthy heart and true only per isoform, compartment or disease state; such verifications need a home.", "achieved": "Nothing merged; proposed projects/AOP_DERIVED_CAUSAL_EVIDENCE_USE_CASES.md. gingin77 added that completion_score 29.41 identifies 1,536 of 2,369 stub KERs and that none of AOP 558's ten citations measures cAMP after PDE inhibition.", "blockers": "AOP-Wiki grades KER3445 High with every evidence section empty; KE693 is tagged Tissue while evidence is subcellular and dismech biological_scale has nothing subcellular either; readout choice (cAMP vs ICa,L) flips disease dependence; a cited cache file is not in the repo.", "methods": [ "FRET cAMP biosensors (Epac2-camps cytosolic, Epac2-alphaKAP SERCA2-targeted)", "patch-clamp ICa,L", "AOP-Wiki completion_score stub-KER check" ], "dismech_records": [] }, "10773": { "number": 10773, "type": "issue", "title": "Keep an inventory of AOP-Wiki data errors found during curation", "url": "https://github.com/monarch-initiative/dismech/issues/10773", "state": "open", "author": "gingin77", "created": "2026-09-03", "closed": null, "assignees": [], "labels": [ "documentation", "enhancement", "low-priority", "evidence" ], "gingin77_role": "author", "group": "aop-use-cases-and-errors", "why": "AOP 552 cited a DOI resolving to a different paper and one that does not resolve; AOP 558's bibliography does not evidence its named step. Nowhere to record such errors.", "achieved": "Nothing merged; a register at projects/AOP_EMOD_ALIGNMENT/aop-wiki-data-errors.md was requested.", "blockers": "Bot sweep: 13 of 16 AOP 552 references defective (8 off-topic, 5 unresolvable); AOPs 552, 558 and 560 share one submitter group with empty OECD tables. Upstream reporting left undecided; mechanical DOI sweep deferred.", "methods": [ "AOP-Wiki reference integrity sweep" ], "dismech_records": [] }, "10456": { "number": 10456, "type": "issue", "title": "AOP-derived content review: add the aop-wiki and mie-ker-capture skills", "url": "https://github.com/monarch-initiative/dismech/issues/10456", "state": "closed", "author": "gingin77", "created": "2026-09-02", "closed": "2026-09-03", "assignees": [], "labels": [ "documentation", "enhancement", "infra" ], "gingin77_role": "author", "group": "aop-skills", "why": "Two locally working skills for turning AOP-Wiki KEs into verified dismech edges needed committing, blocked until aop_wiki_cli was installable.", "achieved": "Closed by #10464.", "blockers": "Blocked on aop_wiki_cli#6 (68-file refactor). KER count discrepancy (2,369 vs 2,361). 29.41 percent is a CLI artefact, so the check is stated as no references, no empirical-support text and no plausibility text. search-with-config only loads packaged configs. AOP-Wiki not citable; a structured source would not make a KER evidence for a mechanism.", "methods": [ "aop-wiki skill", "mie-ker-capture skill" ], "dismech_records": [] }, "10949": { "number": 10949, "type": "issue", "title": "A causal edge cannot carry a confidence, so the claim most in need of one is the claim that cannot express it", "url": "https://github.com/monarch-initiative/dismech/issues/10949", "state": "open", "author": "aleixpuigb", "created": "2026-09-04", "closed": null, "assignees": [], "labels": [ "enhancement", "schema", "discussion" ], "gingin77_role": "commented (authored by another contributor)", "group": "edge-confidence", "why": "mechanism_confidence exists on Pathophysiology only; a CausalEdge cannot say an arrow is a hypothesis.", "achieved": "Nothing merged. gingin77's 2026-09-16 comment: 37,247 downstream edges, 43 percent cited; 8,390 uncited DIRECT edges vs 3,067 declared hedges; AOP-Wiki grades the claim while dismech grades the citation, so the confidence slot should be settled before the #7855 connectivity check.", "blockers": "Maintainer decision needed jointly with the causal_effect polarity question before changing the edge shape.", "methods": [], "dismech_records": [] }, "12682": { "number": 12682, "type": "issue", "title": "Add ToxCast as a structured reference source", "url": "https://github.com/monarch-initiative/dismech/issues/12682", "state": "open", "author": "gingin77", "created": "2026-09-24", "closed": null, "assignees": [ "gingin77" ], "labels": [ "enhancement", "reference-verification", "tooling" ], "gingin77_role": "author", "group": "toxcast-structured-source", "why": "A chemical to assay hit-call is a citable fact nothing in the repository can verify; a fabricated activity claim would pass every gate.", "achieved": "Nothing merged. Specification for a TOXCAST: prefix and per-chemical cache files; reframed as a project issue with the metadata half split to #12858. Hit-call work survives only on an archived local branch.", "blockers": "EPA host fails DNS from sandboxed and CI environments; API key must be requested by email; the sizing paper is paywalled with no PMC deposit; an API-backed source does not fit the sha256 manifest pattern; the assays slot and AssayTerm enum are unvalidatable because OBI is absent from oak_config.", "methods": [ "ToxCast/Tox21 chemical hit-calls as a StructuredSource keyed on DTXSID", "Jeong and Choi 2020 plastic-additive screen as sizing target" ], "dismech_records": [] }, "12858": { "number": 12858, "type": "issue", "title": "Map ToxCast assays to DisMech pathograph nodes using assay metadata", "url": "https://github.com/monarch-initiative/dismech/issues/12858", "state": "open", "author": "gingin77", "created": "2026-09-25", "closed": null, "assignees": [ "gingin77" ], "labels": [ "enhancement", "schema", "tooling" ], "gingin77_role": "author", "group": "toxcast-assay-mapping", "why": "ToxCast assays are molecular-level NAMs; their metadata could map an assay to a pathograph node independently of any chemical result. Measure how far that reaches and whether dismech can represent such a mapping.", "achieved": "Deliverables 1 and 2 landed via #13226 and #13228 (coverage page and THRB worked example); 3 to 5 remain open. 1,570 endpoints, 1,108 with a gene symbol, 497 targets, 1,324 human.", "blockers": "experimental_models is a slot on Disease and links must target a node in the same file, so a disease-agnostic endpoint is copied everywhere with no shared identity. Gene-symbol joins fail by lesion vs state, direction reversal and quantity substitution. No model type for 456 biochemical and 25 cell-free endpoints. 461 endpoints declare no gene. The EPA API has no version endpoint.", "methods": [ "EPA CTX assay-endpoint metadata (gene target, target family, biological process, organism, tissue, assay function, signal direction)", "CTX bioactivity/aop endpoint for AOP-Wiki Key Event links" ], "dismech_records": [ { "name": "TOXCAST", "url": "https://dismech.monarchinitiative.org/pages/projects/TOXCAST.html" }, { "name": "Generalized_Resistance_to_Thyroid_Hormone", "url": "https://dismech.monarchinitiative.org/pages/disorders/Generalized_Resistance_to_Thyroid_Hormone.html" } ] }, "13224": { "number": 13224, "type": "issue", "title": "ToxCast biologicalProcessTarget terms that resolve to GO, and which of them can reach a pathograph node", "url": "https://github.com/monarch-initiative/dismech/issues/13224", "state": "open", "author": "gingin77", "created": "2026-09-30", "closed": null, "assignees": [], "labels": [ "enhancement", "curation" ], "gingin77_role": "author", "group": "toxcast-go-bridges", "why": "biologicalProcessTarget looked like the cheapest bridge from an assay to a node: 38 distinct values, and dismech binds biological_processes to GO.", "achieved": "No PR. A nine-row lookup of the GO-resolving values covering 507 of 1,522 annotated endpoints; H295R identified as the one substantive new bridge to steroid-synthesis nodes.", "blockers": "The top two terms carry 392 of 507 and are too broad to license an edge; honest opportunity is about 115 endpoints. 29 values do not resolve; three carry EPA typos. H295R endpoints list the hormone's receptor as gene target rather than a biosynthetic enzyme. cmungall: GO is only for programmed processes, so toxic cell death must not bind GO cell death.", "methods": [ "ToxCast biologicalProcessTarget vocabulary resolved to GO", "H295R steroidogenesis assay (OECD TG 456, CEETOX and CCTE HTRF endpoints)" ], "dismech_records": [ { "name": "TOXCAST", "url": "https://dismech.monarchinitiative.org/pages/projects/TOXCAST.html" } ] }, "13225": { "number": 13225, "type": "issue", "title": "GO:0051882 mitochondrial depolarization is a narrow, usable ToxCast-to-pathograph bridge", "url": "https://github.com/monarch-initiative/dismech/issues/13225", "state": "open", "author": "gingin77", "created": "2026-09-30", "closed": null, "assignees": [], "labels": [ "enhancement", "curation" ], "gingin77_role": "author", "group": "toxcast-go-bridges", "why": "GO:0051882 mitochondrial depolarization is the narrowest usable bridge in the biologicalProcessTarget vocabulary, already bound by two dismech nodes.", "achieved": "No PR; a scoping analysis. Six endpoints are four measurements; none declares a gene target, so the bridge is invisible to the gene-symbol join, which is what makes it worth having.", "blockers": "fitc and rhodamine are background channels behind the ratio. The HepG2 time series has no place on a readout. Unresolved evidence policy: does an assay measuring a process justify evidence on a node asserting it, or only where a chemical is the recorded cause. Endpoint identity has nowhere to live; no ToxCast endpoint name appears in kb/.", "methods": [ "APR_HepG2_MitoMembPot 1/24/72 h", "TOX21_MMP_ratio, TOX21_MMP_fitc, TOX21_MMP_rhodamine" ], "dismech_records": [ { "name": "PRKN-Related_Juvenile_Parkinson_Disease", "url": "https://dismech.monarchinitiative.org/pages/disorders/PRKN-Related_Juvenile_Parkinson_Disease.html" }, { "name": "Diethylene_Glycol_Poisoning", "url": "https://dismech.monarchinitiative.org/pages/disorders/Diethylene_Glycol_Poisoning.html" }, { "name": "TOXCAST", "url": "https://dismech.monarchinitiative.org/pages/projects/TOXCAST.html" } ] }, "13161": { "number": 13161, "type": "issue", "title": "Add an Endocrine Disruptor Screening History section to the Estrogen Signalling project page", "url": "https://github.com/monarch-initiative/dismech/issues/13161", "state": "closed", "author": "gingin77", "created": "2026-09-29", "closed": "2026-09-30", "assignees": [ "gingin77" ], "labels": [ "documentation", "curation" ], "gingin77_role": "author", "group": "edsp-history", "why": "The estrogen project page claimed ESR1 is among the most heavily assayed ToxCast targets and the receptor the US statute was written around, and cited nothing.", "achieved": "Closed by #13219.", "blockers": "See #13219.", "methods": [ "EDSP Tier 1 screening history", "ToxCast ER and AR pathway models", "OECD TG 455, 493 and 440", "CERAPP and CoMPARA" ], "dismech_records": [ { "name": "ESTROGEN_SIGNALLING", "url": "https://dismech.monarchinitiative.org/pages/projects/ESTROGEN_SIGNALLING.html" } ] }, "13450": { "number": 13450, "type": "issue", "title": "Add the zebrafish VAMR behaviour assay (Spath et al. 2026) to the KB, starting with chlorpyrifos in Organophosphate_Poisoning", "url": "https://github.com/monarch-initiative/dismech/issues/13450", "state": "open", "author": "gingin77", "created": "2026-10-03", "closed": null, "assignees": [], "labels": [ "enhancement", "curation" ], "gingin77_role": "author", "group": "zebrafish-vamr", "why": "The paper tests the VAMR assay on 17 DNT reference chemicals and dismech has no record of the assay; add it one chemical at a time, starting with chlorpyrifos.", "achieved": "Step 1 delivered by #13451 and #13452. Later steps: trichlorfon, ketamine (nmda_receptor_hypofunction), nicotine.", "blockers": "Paper not in PMC; quotable text only via the Zenodo copy; the printed dataset DOI does not resolve. Behaviour only, no AChE measured. Acute and developmental arms move in opposite directions; supplementary tables carry no direction. Text and supplement disagree twice. No node is named for habituation. Core design question: how to represent one assay once so each chemical's result points back to it.", "methods": [ "zebrafish larval Visual and Acoustic Motor Response (VAMR) behaviour assay (Spath et al. 2026, PMID:41780647): acute and developmental arms, 26 endpoints, hit rule >=0.9 with <2 curve-fit flags" ], "dismech_records": [ { "name": "Organophosphate_Poisoning", "url": "https://dismech.monarchinitiative.org/pages/disorders/Organophosphate_Poisoning.html" }, { "name": "nmda_receptor_hypofunction", "url": "https://dismech.monarchinitiative.org/pages/modules/nmda_receptor_hypofunction.html" } ] }, "13749": { "number": 13749, "type": "issue", "title": "Major Depressive Disorder: seed animal_models from C. elegans serotonin, insulin/FOXO and antidepressant-pharmacology work", "url": "https://github.com/monarch-initiative/dismech/issues/13749", "state": "closed", "author": "gingin77", "created": "2026-10-09", "closed": "2026-10-09", "assignees": [ "gingin77" ], "labels": [ "enhancement", "curation" ], "gingin77_role": "author", "group": "celegans-mdd-models", "why": "Major_Depressive_Disorder had twelve pathophysiology nodes, nine treatments and two hypotheses but no animal_models section; worm work is unusually well suited to three of its nodes and to its SSRI and lithium treatments, for the upstream half of the entry rather than the adverse outcome.", "achieved": "Closed by five PRs: #13755 (SSRI mechanism qualified), #13756 (tph-1 and daf-2 models), #13757 (risk-gene panels as a knowledge gap), #13759 (serotonin-to-FOXO arm resolved as HUMAN_MODEL_MISMATCH after an OpenScientist run), #13776 (cross-link and forced-swim citations). Decisions taken: Caenorhabditis elegans as the species string; TPH2 and INSR as human orthologs with alternatives in notes; no insulin/FOXO node.", "blockers": "The worm cannot have depression and nothing may be recorded as modelling the adverse outcome. Orthology is one-to-many (daf-2 to INSR, IGF1R, INSRR; daf-16 to four FOXO genes). The 2024 and 2026 panels are suicidality genes and contain none of the entry's five genes. Every paper in the program shares one senior author and no divergence type expresses single-group provenance. Tier 3 stress-assay papers and a mouse-only paper were flagged as easy to miscite. Fluoxetine-resistance, ketamine-collagen and mianserin papers had nowhere to land.", "methods": [ "tph-1 serotonin-synthesis null C. elegans (Liang 2006, Sze 2000)", "daf-2 insulin-receptor loss-of-function foraging-immobility model (Dagenhardt 2017)", "risk-gene mutant panels in a foraging assay (Sall 2021, Ajayi 2024, Dustin and Dwyer 2026)", "C. elegans fluoxetine, ketamine, lithium and clozapine pharmacology", "scripted PubMed E-utilities survey" ], "dismech_records": [ { "name": "Major_Depressive_Disorder", "url": "https://dismech.monarchinitiative.org/pages/disorders/Major_Depressive_Disorder.html" } ] }, "13754": { "number": 13754, "type": "issue", "title": "Mood disorders record no models at all: promote the model papers already cited, and scope deep research for four gaps", "url": "https://github.com/monarch-initiative/dismech/issues/13754", "state": "open", "author": "gingin77", "created": "2026-10-09", "closed": null, "assignees": [], "labels": [ "enhancement", "curation", "knowledge_gaps" ], "gingin77_role": "author", "group": "mood-disorders-no-models", "why": "All four mood-disorder entries lack animal_models, experimental_models and computational_models, while already citing 14 model-organism papers inside mechanism nodes that are invisible as models.", "achieved": "Nothing merged. The issue separates promotion of already-cited models from four deep-research areas and ranks them; the worm work stayed on #13749. gingin77 noted the schema blocker became #13768 and corrected a bot claim that perturbations exists on ExperimentalModel.", "blockers": "Most depression models are procedures applied to wild-type animals and AnimalModel has no perturbation slot; the stress-paradigm area cannot be curated well until that is resolved. No consensus bipolar mania model; PMDD may have no animal model at all.", "methods": [ "GABA-A delta knockout mouse", "Clock knockdown, GSK-3beta haploinsufficiency and Cacna1c deficiency mice", "ESC/E(Z) patient lymphoblastoid cell model", "chronic unpredictable mild stress, chronic social defeat and learned helplessness paradigms", "hormone-withdrawal postpartum models" ], "dismech_records": [ { "name": "Bipolar_Disorder", "url": "https://dismech.monarchinitiative.org/pages/disorders/Bipolar_Disorder.html" }, { "name": "Major_Depressive_Disorder", "url": "https://dismech.monarchinitiative.org/pages/disorders/Major_Depressive_Disorder.html" } ] }, "13602": { "number": 13602, "type": "issue", "title": "NAMs inventory - what fits and what's fringe", "url": "https://github.com/monarch-initiative/dismech/issues/13602", "state": "open", "author": "gingin77", "created": "2026-10-05", "closed": null, "assignees": [], "labels": [ "question", "schema", "discussion" ], "gingin77_role": "author", "group": "nam-scope", "why": "No stated rule in dismech for when a NAM belongs in a disease entry; a NAM inventory needs a fits, fringe, does-not-fit sorting.", "achieved": "Nothing added; discussion only. Counts on main 2026-10-05: 1,251 models in 600 entries; 212 links lack a relationship.", "blockers": "No structured exposure, dose or duration; no donor-population field; no field for the tie; one model nested in one disease file (the valproate/lithium panel is relevant to four or more entries); CAUSE_UNREPRESENTED was written for computational models. Needs maintainer judgement.", "methods": [ "NAM fit/fringe sorting by what ties the model to the disease" ], "dismech_records": [ { "name": "TOXCAST", "url": "https://dismech.monarchinitiative.org/pages/projects/TOXCAST.html" }, { "name": "NAMO_RD_MODELS", "url": "https://dismech.monarchinitiative.org/pages/projects/NAMO_RD_MODELS.html" } ] }, "13600": { "number": 13600, "type": "issue", "title": "Bipolar Disorder: add a lithium-exposed human neural progenitor model", "url": "https://github.com/monarch-initiative/dismech/issues/13600", "state": "open", "author": "gingin77", "created": "2026-10-05", "closed": null, "assignees": [ "gingin77" ], "labels": [ "enhancement", "curation" ], "gingin77_role": "author", "group": "lithium-npc-model", "why": "Bipolar_Disorder has no experimental_models or animal_models.", "achieved": "Drafted in #13603 (not merged).", "blockers": "Donors are unaffected, so it models how lithium acts on human progenitors, not the disease. No neurogenesis or progenitor node. The dose-response comes from Wolter 2023, not Valone 2026. Genotype-by-treatment effects have no structured field. Heritability and TWAS enrichments are statistical results, not phenotype evidence. Held pending #13602.", "methods": [ "primary human fetal cortical neural progenitors from 83 genotyped unaffected donors exposed to LiCl for 48 h (Wolter 2023, Valone 2026)", "patient iPSC-derived dentate gyrus-like neurons (Mertens 2015)" ], "dismech_records": [ { "name": "Bipolar_Disorder", "url": "https://dismech.monarchinitiative.org/pages/disorders/Bipolar_Disorder.html" } ] }, "13768": { "number": 13768, "type": "issue", "title": "AnimalModel records species as free text and cannot record a non-genetic perturbation: give it the organism and perturbation shape from #13548", "url": "https://github.com/monarch-initiative/dismech/issues/13768", "state": "open", "author": "gingin77", "created": "2026-10-09", "closed": null, "assignees": [], "labels": [ "enhancement", "schema" ], "gingin77_role": "author", "group": "animal-model-organism-perturbation", "why": "AnimalModel records species as free text (66 strings for 2,381 models) and has no slot for a non-genetic perturbation, so stress, diet, surgery, infection and toxin models bury the procedure in genotype, description or category.", "achieved": "Nothing merged. Proposes organism with range OrganismDescriptor, a perturbations list adapted from the EvidencePerturbation design on the #13548 backup branch but allowing a perturbation with no gene, and a gate that checks a model's gene namespace against its organism.", "blockers": "species is an anchor key the entity-ref resolver uses; the 24 unmigrated bound-organism records from #8199 would lose their binding if moved today; #13754 and #13450 are blocked on the slot; the committed datamodel already lags the schema (#13436).", "methods": [ "NCBITaxon-bound organism on AnimalModel", "perturbations list with no required gene on AnimalModel and ExperimentalModel" ], "dismech_records": [] }, "13774": { "number": 13774, "type": "issue", "title": "Nothing enforces the rule that whole-organism models go in animal_models: 50 experimental models still use the pre-#8199 OTHER workaround", "url": "https://github.com/monarch-initiative/dismech/issues/13774", "state": "open", "author": "gingin77", "created": "2026-10-09", "closed": null, "assignees": [], "labels": [ "enhancement", "technical-debt", "tooling" ], "gingin77_role": "author", "group": "animal-model-organism-perturbation", "why": "The rule that whole-organism models go in animal_models is stated in the schema and CLAUDE.md but nothing checks it; 50 experimental_models records carry a non-human organism with type OTHER.", "achieved": "Nothing merged; asks for a just recipe in the style of list-background-citations that lists those 50 and does not fail qc yet.", "blockers": "Migration must wait for #13768 because moving a bound organism into free-text species is the wrong direction; some OTHER records are legitimate ESC-derived NAMs mistyped for a different reason (#12806).", "methods": [ "report-only check for whole-organism models parked in experimental_models" ], "dismech_records": [] }, "11140": { "number": 11140, "type": "issue", "title": "Document that animal model genes are recorded as human orthologs", "url": "https://github.com/monarch-initiative/dismech/issues/11140", "state": "open", "author": "dragon-ai-agent", "created": "2026-09-05", "closed": null, "assignees": [], "labels": [ "documentation" ], "gingin77_role": "commented (authored by dragon-ai-agent)", "group": "model-gene-namespaces", "why": "animal_models record genes as human HGNC identifiers in 330 of 995 entries and the convention is documented nowhere.", "achieved": "Nothing merged. gingin77's four comments, from the worm survey in #13749, showed the convention is underdetermined for one-to-many orthology (tph-1 two candidates, daf-2 three, daf-16 four), that nine MGI bindings already break it, that a zebrafish entry keeps the paralog in preferred_term, and that #13548 changes the convention so the documentation should describe the new rule.", "blockers": "Documentation written against the old rule would be wrong within weeks; a mouse dataset binding MGI sits outside the new gate's scope.", "methods": [ "human-ortholog convention on model genes vs species-native identifiers" ], "dismech_records": [ { "name": "Major_Depressive_Disorder", "url": "https://dismech.monarchinitiative.org/pages/disorders/Major_Depressive_Disorder.html" } ] }, "11427": { "number": 11427, "type": "issue", "title": "No way to say \"this phenotype is the readout of this mechanism\", so curators borrow `sequelae` and get a reversed edge", "url": "https://github.com/monarch-initiative/dismech/issues/11427", "state": "open", "author": "gingin77", "created": "2026-09-08", "closed": null, "assignees": [], "labels": [ "schema", "discussion" ], "gingin77_role": "author", "group": "phenotype-readout", "why": "Curators wanting to say a phenotype is the readout of a mechanism borrow sequelae, which compiles to a phenotype-to-target edge and reverses causation; nine such edges in six files.", "achieved": "Nothing merged.", "blockers": "The construct already exists as Phenotype.reports_on, used in over 150 files, so this is a discoverability gap. Recommended: reports_on migration plus one CLAUDE.md sentence; skip a heuristic gate.", "methods": [ "Phenotype.reports_on / PhenotypeReadout (READOUT_OF, CORRELATES_WITH, PREDICTS, PHARMACODYNAMIC_MARKER_OF)" ], "dismech_records": [] }, "9421": { "number": 9421, "type": "issue", "title": "`EvidenceItem` records where a claim came from but not how strong it is: no study design, sample size, or validity classification", "url": "https://github.com/monarch-initiative/dismech/issues/9421", "state": "open", "author": "matentzn", "created": "2026-08-24", "closed": null, "assignees": [], "labels": [ "enhancement", "schema" ], "gingin77_role": "commented (authored by another contributor)", "group": "evidence-strength-assay-typing", "why": "EvidenceItem records where a claim came from but not how strong it is: an n=1 case report and an RCT are indistinguishable.", "achieved": "Nothing merged. gingin77's 2026-09-04 comment cross-referenced #10772: ECO types the evidence, OBI types the assay; 564 assay entries, none OBI-bound; letting an evidence item point at its model matches EMOD's indirection, so one schema change should probably cover both issues.", "blockers": "cmungall ruled agents were redoing a hackathon discussion and that RCT tiers do not suit pathograph internals; do not duplicate ClinGen. publication_types present in only 8.5 percent of the cache; ECO cannot express study design.", "methods": [ "ECO vs OBI assay typing (via gingin77's comment)" ], "dismech_records": [] } }, "prs": { "9931": { "number": 9931, "type": "pr", "title": "curate(NSCLC): ground the organ-chip TKI readout in GO (#9792)", "url": "https://github.com/monarch-initiative/dismech/pull/9931", "state": "merged", "author": "gingin77", "created": "2026-08-28", "merged": "2026-08-29", "draft": false, "files_changed": [ "history/disorders/Non-Small_Cell_Lung_Cancer/2026-08-28T195105Z-claude-code-5b4640.yaml", "kb/disorders/Non-Small_Cell_Lung_Cancer.yaml" ], "labels": [], "gingin77_role": "author", "group": "nsclc-organ-chip", "why": "The TKI-response readout said it measured EGFR/MET signalling only in prose; this makes it machine-queryable.", "achieved": "Added biological_processes GO:0007169 to the Tyrosine kinase inhibitor therapeutic response readout, matching the Oncogenic Driver Mutations target node. Relationship kept at MEASURES because the chip never claims to reproduce a driver lesion.", "blockers": "Reviewer approved with non-blocking notes: preferred_term reads as a sentence; the growth/dormancy and invasion-under-strain readouts remain ungrounded.", "methods": [ "lung organ-chip TKI therapeutic-response readout grounded in GO:0007169" ], "dismech_records": [ { "name": "Non-Small_Cell_Lung_Cancer", "url": "https://dismech.monarchinitiative.org/pages/disorders/Non-Small_Cell_Lung_Cancer.html" } ] }, "9665": { "number": 9665, "type": "pr", "title": "Add experimental_models NAM records for DCM, NSCLC, and EAC", "url": "https://github.com/monarch-initiative/dismech/pull/9665", "state": "merged", "author": "mellybelly", "created": "2026-08-27", "merged": "2026-08-28", "draft": false, "files_changed": [ "history/disorders/Dilated_Cardiomyopathy/2026-08-27T144116Z-claude-code-b4c01c.yaml", "history/disorders/Esophageal_Adenocarcinoma/2026-08-27T144116Z-claude-code-a3b553.yaml", "history/disorders/Esophageal_Adenocarcinoma/2026-08-27T180048Z-claude-code-816f33.yaml", "history/disorders/Non-Small_Cell_Lung_Cancer/2026-08-27T144116Z-claude-code-ebb95f.yaml", "history/disorders/Non-Small_Cell_Lung_Cancer/2026-08-27T180048Z-claude-code-fa88cb.yaml", "kb/disorders/Dilated_Cardiomyopathy.yaml", "kb/disorders/Esophageal_Adenocarcinoma.yaml", "kb/disorders/Non-Small_Cell_Lung_Cancer.yaml" ], "labels": [], "gingin77_role": "related (authored by mellybelly)", "group": "nsclc-organ-chip", "why": "Turn three NAMeRS evidence items into structured experimental_models records.", "achieved": "Added ORGAN_ON_CHIP and iPSC records for DCM, NSCLC and EAC; the NSCLC record is the one #9792 asked for.", "blockers": "See #9792 for gingin77's objections to the NSCLC links.", "methods": [ "experimental_models NAM records for DCM, NSCLC and EAC" ], "dismech_records": [ { "name": "Dilated_Cardiomyopathy", "url": "https://dismech.monarchinitiative.org/pages/disorders/Dilated_Cardiomyopathy.html" }, { "name": "Non-Small_Cell_Lung_Cancer", "url": "https://dismech.monarchinitiative.org/pages/disorders/Non-Small_Cell_Lung_Cancer.html" }, { "name": "Esophageal_Adenocarcinoma", "url": "https://dismech.monarchinitiative.org/pages/disorders/Esophageal_Adenocarcinoma.html" } ] }, "9797": { "number": 9797, "type": "pr", "title": "curate(Esophageal_Squamous_Cell_Carcinoma): patient-derived organoid NAM record and chemotherapy-resistance node", "url": "https://github.com/monarch-initiative/dismech/pull/9797", "state": "merged", "author": "gingin77", "created": "2026-08-28", "merged": "2026-08-28", "draft": false, "files_changed": [ "history/disorders/Esophageal_Squamous_Cell_Carcinoma/2026-08-28T032410Z-claude-code-f4c5ad.yaml", "kb/disorders/Esophageal_Squamous_Cell_Carcinoma.yaml", "references_cache/PMID_40169778.md" ], "labels": [ "curation" ], "gingin77_role": "author", "group": "escc-organoid", "why": "Give ESCC its first NAM record and connect it to the pathograph.", "achieved": "New experimental_models entry (UBERON esophagus, CL:0002252) linked to a new Chemotherapy Resistance node (GO:0034599, cisplatin/5-FU sensitivity, antioxidant stress-response and fedratinib readouts) and to TP53 Dysfunction, both RECAPITULATES at MODERATE fidelity; six snippets verified.", "blockers": "The new node is isolated because the paper does not show which upstream node produces the antioxidant state and no recurrence phenotype exists downstream. Organoids are tumour-cell-only; the p53 stain misses truncating alleles. Reviewer suggested NFE2L2 and ALDH3A1/SPP1/TXNRD1 follow-ups.", "methods": [ "24-patient ESCC patient-derived organoid library, ORGANOID / namo:Organoid" ], "dismech_records": [ { "name": "Esophageal_Squamous_Cell_Carcinoma", "url": "https://dismech.monarchinitiative.org/pages/disorders/Esophageal_Squamous_Cell_Carcinoma.html" } ] }, "10573": { "number": 10573, "type": "pr", "title": "fix(Stargardt_Disease, Noonan_Syndrome, Ulcerative_Colitis): link NAM experimental models into the pathograph (#10432)", "url": "https://github.com/monarch-initiative/dismech/pull/10573", "state": "merged", "author": "app/ai4c-agent", "created": "2026-09-02", "merged": "2026-09-05", "draft": false, "files_changed": [ "history/disorders/Noonan_Syndrome/2026-09-02T162917Z-claude-code-5faaae.yaml", "history/disorders/Stargardt_Disease/2026-09-02T162909Z-claude-code-6c0ede.yaml", "history/disorders/Ulcerative_Colitis/2026-09-02T162924Z-claude-code-851078.yaml", "kb/disorders/Noonan_Syndrome.yaml", "kb/disorders/Stargardt_Disease.yaml", "kb/disorders/Ulcerative_Colitis.yaml", "projects/NAMO_RD_MODELS.md" ], "labels": [ "scope-override" ], "gingin77_role": "related (authored by ai4c-agent, closes gingin77's issue)", "group": "namo-seven-models", "why": "Close #10432 by linking the seven models.", "achieved": "Stargardt: retinal organoid to ABCA4 transporter dysfunction (MEASURES) and photoreceptor degeneration; iPSC-RPE to endo-lysosomal dysfunction (RECAPITULATES). Noonan: cortical organoid to cortical layer abnormalities; iPSC-CM to cardiomyocyte hypertrophy and ERK hyperactivation (PERTURBS). UC: colonoid, colon organoid and colon-on-chip to barrier dysfunction and dysregulated immune response.", "blockers": "As on #10432.", "methods": [ "retinal organoid", "iPSC-RPE", "cortical organoid", "iPSC-cardiomyocytes", "air-liquid-interface colonoid", "cytokine-conditioned hiPSC colon organoid", "colon-on-chip" ], "dismech_records": [ { "name": "Stargardt_Disease", "url": "https://dismech.monarchinitiative.org/pages/disorders/Stargardt_Disease.html" }, { "name": "Noonan_Syndrome", "url": "https://dismech.monarchinitiative.org/pages/disorders/Noonan_Syndrome.html" }, { "name": "Ulcerative_Colitis", "url": "https://dismech.monarchinitiative.org/pages/disorders/Ulcerative_Colitis.html" } ] }, "10430": { "number": 10430, "type": "pr", "title": "Link the NAMO_RD_MODELS project page to the diseases it lists", "url": "https://github.com/monarch-initiative/dismech/pull/10430", "state": "merged", "author": "gingin77", "created": "2026-09-01", "merged": "2026-09-04", "draft": false, "files_changed": [ "projects/NAMO_RD_MODELS.md" ], "labels": [], "gingin77_role": "author", "group": "namo-seven-models", "why": "The NAMO_RD_MODELS project page listed five diseases but declared none in frontmatter and used prose names, so it rendered with no links and an empty sidebar.", "achieved": "Docs only: declared the five diseases, added MODELS/NAM/RARE_DISEASE/CROSSWALK tags, corrected the Bhatt note. Confirmed all five carry namo_type-bound models.", "blockers": "Tokens with a trailing hyphen do not auto-link; the PR body double-counted links and undercounted Crohn models. Non-blocking.", "methods": [], "dismech_records": [ { "name": "Cystic_Fibrosis", "url": "https://dismech.monarchinitiative.org/pages/disorders/Cystic_Fibrosis.html" }, { "name": "Stargardt_Disease", "url": "https://dismech.monarchinitiative.org/pages/disorders/Stargardt_Disease.html" }, { "name": "Noonan_Syndrome", "url": "https://dismech.monarchinitiative.org/pages/disorders/Noonan_Syndrome.html" }, { "name": "Crohn_Disease", "url": "https://dismech.monarchinitiative.org/pages/disorders/Crohn_Disease.html" }, { "name": "Ulcerative_Colitis", "url": "https://dismech.monarchinitiative.org/pages/disorders/Ulcerative_Colitis.html" }, { "name": "NAMO_RD_MODELS", "url": "https://dismech.monarchinitiative.org/pages/projects/NAMO_RD_MODELS.html" } ] }, "12582": { "number": 12582, "type": "pr", "title": "Link NAM and animal models into the pathograph for six #802 target diseases", "url": "https://github.com/monarch-initiative/dismech/pull/12582", "state": "merged", "author": "gingin77", "created": "2026-09-23", "merged": "2026-09-23", "draft": false, "files_changed": [ "history/disorders/BBSome-Related_Retinitis_Pigmentosa/2026-09-23T134755Z-claude-code-cdaa7b.yaml", "history/disorders/BBSome-Related_Retinitis_Pigmentosa/2026-09-23T141909Z-claude-code-6cc25f.yaml", "history/disorders/BRAF_V600E_Mutant_Colorectal_Cancer/2026-09-23T134756Z-claude-code-f90020.yaml", "history/disorders/BRAF_V600E_Mutant_Colorectal_Cancer/2026-09-23T141909Z-claude-code-26aa59.yaml", "history/disorders/Leber_Congenital_Amaurosis_10/2026-09-23T134756Z-claude-code-309ff2.yaml", "history/disorders/Leber_Congenital_Amaurosis_10/2026-09-23T141909Z-claude-code-9550b2.yaml", "history/disorders/MSI_High_Colorectal_Cancer/2026-09-23T134756Z-claude-code-e66ca0.yaml", "history/disorders/MSI_High_Colorectal_Cancer/2026-09-23T141909Z-claude-code-6f0e0a.yaml", "history/disorders/Tuberous_Sclerosis_Complex/2026-09-23T134756Z-claude-code-ccc857.yaml", "history/disorders/Tuberous_Sclerosis_Complex/2026-09-23T141909Z-claude-code-20ad70.yaml", "history/disorders/Wilsons_Disease/2026-09-23T134755Z-claude-code-00b612.yaml", "kb/disorders/BBSome-Related_Retinitis_Pigmentosa.yaml", "kb/disorders/BRAF_V600E_Mutant_Colorectal_Cancer.yaml", "kb/disorders/Leber_Congenital_Amaurosis_10.yaml", "kb/disorders/MSI_High_Colorectal_Cancer.yaml", "kb/disorders/Tuberous_Sclerosis_Complex.yaml", "kb/disorders/Wilsons_Disease.yaml", "references_cache/PMID_21593220.md", "references_cache/PMID_27151457.md", "references_cache/PMID_29674751.md", "references_cache/PMID_30100188.md", "references_cache/PMID_30114557.md", "references_cache/PMID_30127391.md", "references_cache/PMID_33097693.md", "references_cache/PMID_35084981.md", "references_cache/PMID_42190325.md" ], "labels": [], "gingin77_role": "author", "group": "nam-target-diseases", "why": "First pass at the NAM-linkage checklist gingin77 wrote on #802.", "achieved": "Linked animal and NAM models into the pathograph for six target diseases, including a RESCUES link on the Wilson organoid, a FAILS_TO_RECAPITULATE link on the TSC second-hit node and a MEASURES link with PROXY_QUANTITY divergence on BRAF CRC; nine cache files, 755/755 snippets.", "blockers": "Reviewer requested changes (all fixed): a three-word snippet, a TSC limitation that wrongly said not patient-derived, two TSC models making opposite second-hit claims (CONTESTED_ASSUMPTION, fidelity lowered), an overstated LCA10 opsin link, a coarse cell-type term, missing BBS model names. Wilson organoid fidelity stays UNKNOWN because the abstract names no assay. BBS iPSC lines characterise pluripotency only and were left unlinked.", "methods": [ "BBSome RP animal models", "ATP7B R778L and H1069Q iPSC hepatocyte-like cells", "prime-edited patient liver organoids", "CEP290 patient optic cups", "QR-110-treated retinal organoids", "TSC2 cortical spheroids", "patient cerebral organoids", "BRAF V600E PDO/PDOX biobank", "autologous organoid plus peripheral blood lymphocyte co-culture" ], "dismech_records": [ { "name": "BBSome-Related_Retinitis_Pigmentosa", "url": "https://dismech.monarchinitiative.org/pages/disorders/BBSome-related_retinitis_pigmentosa.html" }, { "name": "Wilsons_Disease", "url": "https://dismech.monarchinitiative.org/pages/disorders/Wilson_Disease.html" }, { "name": "Leber_Congenital_Amaurosis_10", "url": "https://dismech.monarchinitiative.org/pages/disorders/Leber_Congenital_Amaurosis_10.html" }, { "name": "Tuberous_Sclerosis_Complex", "url": "https://dismech.monarchinitiative.org/pages/disorders/Tuberous_Sclerosis_Complex.html" }, { "name": "BRAF_V600E_Mutant_Colorectal_Cancer", "url": "https://dismech.monarchinitiative.org/pages/disorders/BRAF_V600E-Mutant_Colorectal_Cancer.html" }, { "name": "MSI_High_Colorectal_Cancer", "url": "https://dismech.monarchinitiative.org/pages/disorders/MSI-High_Colorectal_Cancer.html" } ] }, "9935": { "number": 9935, "type": "pr", "title": "curate(Liver_Cirrhosis, DILI module): first liver fibrosis NAM", "url": "https://github.com/monarch-initiative/dismech/pull/9935", "state": "merged", "author": "gingin77", "created": "2026-08-28", "merged": "2026-08-29", "draft": false, "files_changed": [ "history/disorders/Liver_Cirrhosis/2026-08-28T203748Z-claude-code-c63015.yaml", "history/modules/drug_induced_liver_injury/2026-08-28T203757Z-claude-code-55b462.yaml", "kb/disorders/Liver_Cirrhosis.yaml", "kb/modules/drug_induced_liver_injury.yaml", "references_cache/PMID_40754287.md" ], "labels": [], "gingin77_role": "author", "group": "liver-fibrosis-mps", "why": "The three existing liver models were all drug-toxicity models on the DILI module; Liver_Cirrhosis, MASLD, alcoholic liver disease and fibrotic_response had no experimental models at all.", "achieved": "Added the MPS as a CO_CULTURE / namo:CoCulture experimental_models entry on Liver_Cirrhosis and the DILI module, linked to Hepatic Stellate Cell Activation (RECAPITULATES), Kupffer Cell and Inflammatory Response and Hepatocyte Injury and Death (PARTIALLY_RECAPITULATES), TGF-beta Signaling (PERTURBS), and two DILI nodes; 15 evidence items, all snippets verified.", "blockers": "No NAMO class fit until namo:CoCulture was found among NAMO's 56 classes; namo:MicrophysiologicalSystem requires microfluidics the gravity-linked plate lacks. THP-1 activation is TGF-beta1-driven, not drug-driven, so the drug to inflammation step is undemonstrated and fidelity is LOW. Exogenous TGF-beta1 forces PERTURBS. The paper is abstract-only and only the PMID validates.", "methods": [ "Akura Twin 384-well liver fibrosis microphysiological system (Schmidt and Suter-Dick 2025, PMID:40754287): HepaRG hepatocyte microtissues with THP-1 monocytes paired with hTERT-HSC stellate microtissues, challenged with TGF-beta1, methotrexate and acetaminophen" ], "dismech_records": [ { "name": "Liver_Cirrhosis", "url": "https://dismech.monarchinitiative.org/pages/disorders/Liver_Cirrhosis.html" }, { "name": "drug_induced_liver_injury", "url": "https://dismech.monarchinitiative.org/pages/modules/drug_induced_liver_injury.html" } ] }, "10282": { "number": 10282, "type": "pr", "title": "enhance(fibrotic_response): add Scar-in-a-Jar module-level experimental model (#9997)", "url": "https://github.com/monarch-initiative/dismech/pull/10282", "state": "merged", "author": "gingin77", "created": "2026-08-31", "merged": "2026-08-31", "draft": false, "files_changed": [ "history/modules/fibrotic_response/2026-08-31T194022Z-claude-code-5a9798.yaml", "history/modules/fibrotic_response/2026-08-31T224818Z-claude-code-012cbf.yaml", "history/modules/fibrotic_response/2026-08-31T234401Z-claude-code-d2b620.yaml", "kb/modules/fibrotic_response.yaml", "references_cache/PMID_32381012.md", "references_cache/PMID_33521022.md", "references_cache/PMID_34028741.md" ], "labels": [], "gingin77_role": "author", "group": "fibrotic-response-models", "why": "Give the most-reused module its first experimental model using an organ-agnostic published platform.", "achieved": "Added the assay to fibrotic_response linked to Mesenchymal Cell Activation and Excessive ECM Deposition (RECAPITULATES, MODERATE) with alpha-SMA, ACTA2, PRO-C1/PRO-C6, FBN-C and MMP1/CTSK readouts; three new reference caches, 20/20 snippets. Tissue Injury, Inflammatory Recruitment and Architectural Distortion deliberately not linked.", "blockers": "Two CHANGES_REQUESTED rounds for readouts asserting direction on Methods-only quotes, and a third on readout naming and modality. tissue_term omitted with a notes justification. The protocol chapter's evidence_source regraded to OTHER. Limitations: exogenous TGF-beta1 bypasses latent activation, alpha-SMA separates only after day 8, 2D matrix, production arm only. just validate-modules not completed locally.", "methods": [ "Scar-in-a-Jar macromolecular crowding assay (Stebler and Raghunath 2021, PMID:34028741) with dermal (PMID:33521022) and lung (PMID:32381012) fibroblast demonstrations" ], "dismech_records": [ { "name": "fibrotic_response", "url": "https://dismech.monarchinitiative.org/pages/modules/fibrotic_response.html" } ] }, "10257": { "number": 10257, "type": "pr", "title": "docs(AOP): worked example mapping AOP 38 to the liver fibrosis NAM (#10051)", "url": "https://github.com/monarch-initiative/dismech/pull/10257", "state": "merged", "author": "gingin77", "created": "2026-08-31", "merged": "2026-08-31", "draft": false, "files_changed": [ "history/disorders/Liver_Cirrhosis/2026-08-29T171518Z-claude-code-1e13fe.yaml", "history/modules/fibrotic_response/2026-08-29T171527Z-claude-code-299866.yaml", "kb/disorders/Liver_Cirrhosis.yaml", "kb/modules/fibrotic_response.yaml", "projects/AOP_EMOD_ALIGNMENT.md" ], "labels": [ "scope-override" ], "gingin77_role": "author", "group": "aop38-bridge-test", "why": "Record the AOP 38 to Akura Twin Key Event correspondence as the first worked test of the Assay/NAM bridge.", "achieved": "Seven-row correspondence table (five of seven KEs map, both endpoints miss), the acetaminophen analysis, eight biological_scale values on Liver_Cirrhosis and fibrotic_response, and a new Open schema questions section.", "blockers": "Kupffer node left untagged because biological_scale is single-valued and it maps to a cellular and a tissue KE. Scope guard rejected projects/ on a PR touching kb/ (needed scope-override). Reviewer could not verify any AOP-Wiki number without the CLI and asked for an export name and hash.", "methods": [ "AOP 38 worked example", "biological_scale tagging" ], "dismech_records": [ { "name": "Liver_Cirrhosis", "url": "https://dismech.monarchinitiative.org/pages/disorders/Liver_Cirrhosis.html" }, { "name": "fibrotic_response", "url": "https://dismech.monarchinitiative.org/pages/modules/fibrotic_response.html" }, { "name": "AOP_EMOD_ALIGNMENT", "url": "https://dismech.monarchinitiative.org/pages/projects/AOP_EMOD_ALIGNMENT.html" } ] }, "10299": { "number": 10299, "type": "pr", "title": "docs(AOP): stop conflating liver fibrosis with cirrhosis in the AOP 38 mapping", "url": "https://github.com/monarch-initiative/dismech/pull/10299", "state": "merged", "author": "gingin77", "created": "2026-08-31", "merged": "2026-08-31", "draft": false, "files_changed": [ "projects/AOP_EMOD_ALIGNMENT.md" ], "labels": [], "gingin77_role": "author", "group": "aop38-bridge-test", "why": "#10257 matched AO 344 Increase, Liver fibrosis to the Liver_Cirrhosis entry, conflating fibrosis with cirrhosis in the one place the page was meant to demonstrate that distinction.", "achieved": "AO row recorded as unmapped: dismech has no organ-level liver-fibrosis event. Six passages corrected; open schema question 2 reframed.", "blockers": "The real gap is curation, not schema, and cannot be settled until that node exists. Reviewer notes: Alcoholic_Liver_Disease already splits the two events and would give the gap a template.", "methods": [], "dismech_records": [ { "name": "Liver_Cirrhosis", "url": "https://dismech.monarchinitiative.org/pages/disorders/Liver_Cirrhosis.html" }, { "name": "AOP_EMOD_ALIGNMENT", "url": "https://dismech.monarchinitiative.org/pages/projects/AOP_EMOD_ALIGNMENT.html" } ] }, "10002": { "number": 10002, "type": "pr", "title": "AOP/EMOD framework alignment: the project page and the lead use case (#8309)", "url": "https://github.com/monarch-initiative/dismech/pull/10002", "state": "merged", "author": "gingin77", "created": "2026-08-29", "merged": "2026-08-29", "draft": false, "files_changed": [ "projects/AOP_EMOD_ALIGNMENT.md", "projects/AOP_EMOD_ALIGNMENT/artifacts/lead_aop_consensus_network.json", "projects/AOP_EMOD_ALIGNMENT/artifacts/lead_aop_final_consensus_network.json", "projects/AOP_EMOD_ALIGNMENT/artifacts/lead_aop_network.json", "projects/AOP_EMOD_ALIGNMENT/assessments/openscientist-assessment-by-claude-code.yaml", "projects/AOP_EMOD_ALIGNMENT/openscientist-lead-aop-network.md", "projects/AOP_EMOD_ALIGNMENT/working-notes-2026-08-12.md", "references_cache/PMID_25466378.md", "references_cache/PMID_25466379.md" ], "labels": [], "gingin77_role": "author", "group": "aop-emod-alignment", "why": "Deliver the alignment page and the lead pilot from #8309.", "achieved": "projects/AOP_EMOD_ALIGNMENT.md plus artifacts. Findings: 20 of 36 lead KERs cite nothing, 18 of those graded High; 14 of 35 KEs map cleanly to module nodes, 7 partial, 14 none; all five chemical MIEs have nowhere to attach; glutamate_excitotoxicity is sign-inverted against lead NMDA inhibition.", "blockers": "Reviewer REQUEST_CHANGES over a false claim that a cardiomyopathy module starts at a genetic variant, a stale module census, an arithmetic error and missing frontmatter. OpenScientist's calcium-mimicry claim rejected; a plant-study PMID used for a cardiac claim; sidecar outside the CI glob (#9986). No KB or schema change.", "methods": [ "lead AOP network (AOPs 12, 499, 500, 552, 555, 556, 558, 560) with OpenScientist report and claim-by-claim assessment" ], "dismech_records": [ { "name": "Lead_Poisoning", "url": "https://dismech.monarchinitiative.org/pages/disorders/Lead_Poisoning.html" }, { "name": "AOP_EMOD_ALIGNMENT", "url": "https://dismech.monarchinitiative.org/pages/projects/AOP_EMOD_ALIGNMENT.html" } ] }, "10760": { "number": 10760, "type": "pr", "title": "docs(AOP): why the pilot comparator changed, and that an AOP is not a mechanism boundary", "url": "https://github.com/monarch-initiative/dismech/pull/10760", "state": "merged", "author": "gingin77", "created": "2026-09-03", "merged": "2026-09-05", "draft": false, "files_changed": [ "projects/AOP_EMOD_ALIGNMENT.md" ], "labels": [], "gingin77_role": "author", "group": "aop-not-a-boundary", "why": "Land #10344's edits and the 'AOP is provenance, not structure' finding from #10687.", "achieved": "Comparator rationale, ADME point beside the toxicokinetics row, a new divergence row, and three rules: AOP ID on the edge, never a grouping key, recover mechanisms via connected components over shared KEs.", "blockers": "Second commit withdrew both measurements and the tool pointer after a networkFinder render disagreed; reviewer noted the many-to-many claim is now unsupported on the page.", "methods": [], "dismech_records": [ { "name": "AOP_EMOD_ALIGNMENT", "url": "https://dismech.monarchinitiative.org/pages/projects/AOP_EMOD_ALIGNMENT.html" } ] }, "11394": { "number": 11394, "type": "pr", "title": "docs(AOP): how each model records the way a claim was measured", "url": "https://github.com/monarch-initiative/dismech/pull/11394", "state": "merged", "author": "gingin77", "created": "2026-09-07", "merged": "2026-09-08", "draft": false, "files_changed": [ "projects/AOP_EMOD_ALIGNMENT.md" ], "labels": [], "gingin77_role": "author", "group": "how-a-claim-was-measured", "why": "Record the measurement-method gap on the alignment page.", "achieved": "One divergence row and a subsection: 564 assay entries in 87 files, zero bound to any OBI term, only 2 on a pathophysiology node; Pathophysiology.assays corresponds to EMOD Event.assays. Cross-link posted on #9421.", "blockers": "No schema change; a back-pointer from evidence item to model recorded as the likely single fix. Reviewer nits on a population claim and a missing relationship_id.", "methods": [ "ECO vs OBI distinction with worked terms (ECO:0006014, OBI:0002178)" ], "dismech_records": [ { "name": "AOP_EMOD_ALIGNMENT", "url": "https://dismech.monarchinitiative.org/pages/projects/AOP_EMOD_ALIGNMENT.html" } ] }, "10464": { "number": 10464, "type": "pr", "title": "Add the aop-wiki and mie-ker-capture skills", "url": "https://github.com/monarch-initiative/dismech/pull/10464", "state": "merged", "author": "gingin77", "created": "2026-09-02", "merged": "2026-09-03", "draft": false, "files_changed": [ ".claude/skills/aop-wiki/SKILL.md", ".claude/skills/ker-evidence-triage/SKILL.md", ".claude/skills/mie-ker-capture/SKILL.md", ".gitignore" ], "labels": [], "gingin77_role": "author", "group": "aop-skills", "why": "Commit the skills now that aop-wiki-cli is uvx-installable.", "achieved": "Three skills with the stub-KER gate and scoring proof, bibliography-to-step mapping, connected-components rule, and the finding that conforms_to is not the test (60 percent of disorders declare none).", "blockers": "Two REQUEST_CHANGES rounds over a wrong KE example and a false config sentence; gingin77 held the PR to fix a claim that KEs are organ-agnostic (they carry cell and organ terms). Unpinned uvx git ref; upstream CLI bugs still to file.", "methods": [ "aop-wiki, mie-ker-capture and ker-evidence-triage skills" ], "dismech_records": [], "supporting_files": [ { "path": ".claude/skills/aop-wiki/SKILL.md", "url": "https://github.com/monarch-initiative/dismech/blob/main/.claude/skills/aop-wiki/SKILL.md" }, { "path": ".claude/skills/mie-ker-capture/SKILL.md", "url": "https://github.com/monarch-initiative/dismech/blob/main/.claude/skills/mie-ker-capture/SKILL.md" }, { "path": ".claude/skills/ker-evidence-triage/SKILL.md", "url": "https://github.com/monarch-initiative/dismech/blob/main/.claude/skills/ker-evidence-triage/SKILL.md" } ] }, "11852": { "number": 11852, "type": "pr", "title": "Which dismech pathographs could seed Adverse Outcome Pathways", "url": "https://github.com/monarch-initiative/dismech/pull/11852", "state": "merged", "author": "gingin77", "created": "2026-09-15", "merged": "2026-09-16", "draft": false, "files_changed": [ "docs/reports/aop-derivable-measurable-chains-2026-09-10.md", "mkdocs.yml", "project.justfile", "projects/AOP_EMOD_ALIGNMENT.md", "projects/AOP_EMOD_ALIGNMENT/putative-aops-from-dismech-2026-09-10.md", "scripts/aop_chain_census.py" ], "labels": [], "gingin77_role": "author", "group": "seed-aops-from-dismech", "why": "Find which entries hold a connected, node-measured, edge-cited causal chain usable as an AOP backbone, and work two into AOP-Wiki v2.8 vocabulary.", "achieved": "Census report, derivations file and committed script. Edge evidence is about thirty-five times more available than node measurability; only LVNC8 clears both screens at five or more nodes; the constraint on deriving AOPs is modeled_mechanisms coverage, not more reading.", "blockers": "Exposures never reach an MIE because every exposure edge lands on a toxicokinetic node and nothing marks such nodes. KE 18 AhR activation cannot be reused for fluorosis's AhR under-activation. Three terminal fluorosis events have no AOP-Wiki counterpart. Six review rounds over a mislabelled table.", "methods": [ "AOP chain census (just aop-chain-census)" ], "dismech_records": [ { "name": "Left_Ventricular_Noncompaction_8", "url": "https://dismech.monarchinitiative.org/pages/disorders/Left_Ventricular_Noncompaction_8.html" }, { "name": "Skeletal_Fluorosis", "url": "https://dismech.monarchinitiative.org/pages/disorders/Skeletal_Fluorosis.html" }, { "name": "Lead_Poisoning", "url": "https://dismech.monarchinitiative.org/pages/disorders/Lead_Poisoning.html" }, { "name": "AOP_EMOD_ALIGNMENT", "url": "https://dismech.monarchinitiative.org/pages/projects/AOP_EMOD_ALIGNMENT.html" } ], "supporting_files": [ { "path": "scripts/aop_chain_census.py", "url": "https://github.com/monarch-initiative/dismech/blob/main/scripts/aop_chain_census.py" }, { "path": "docs/reports/aop-derivable-measurable-chains-2026-09-10.md", "url": "https://github.com/monarch-initiative/dismech/blob/main/docs/reports/aop-derivable-measurable-chains-2026-09-10.md" } ] }, "11857": { "number": 11857, "type": "pr", "title": "Add TDAR AOP project: compare the TDAR adverse outcome pathways against dismech's humoral-immunity modules", "url": "https://github.com/monarch-initiative/dismech/pull/11857", "state": "merged", "author": "gingin77", "created": "2026-09-15", "merged": "2026-09-16", "draft": false, "files_changed": [ "projects/TDAR_AOP.md", "projects/TDAR_AOP/artifacts/tdar_aop_network.json", "projects/TDAR_AOP/artifacts/tdar_aop_network.png", "projects/TDAR_AOP/artifacts/tdar_infection_aop_network.json", "projects/TDAR_AOP/artifacts/tdar_infection_aop_network.png", "projects/TDAR_AOP/openscientist-tdar-aop-network.md" ], "labels": [], "gingin77_role": "author", "group": "tdar-aop", "why": "Three AOP-Wiki pathways end at impaired TDAR, a standard immunotoxicology endpoint; read them against how dismech models antibody immunity.", "achieved": "projects/TDAR_AOP.md with the report and two network diagrams. TDAR adverse outcomes are terminal with zero downstream KERs; the one quantitative bridge describes concanavalin A proliferation; Luster 1993 says no single immune test predicts host resistance; Orange 2010 gives a strong human dose-response once reframed as impaired antibody response; both frameworks stop one node short of infection.", "blockers": "The commissioned linkage is not curated anywhere; AOP 277's infection outcome was orphaned during OECD review. The report's citations have not passed validate-research-references and it contradicts the verification in two places. No new module proposed.", "methods": [ "T-cell dependent antibody response (TDAR) assay as an AOP endpoint", "concanavalin A splenocyte proliferation (the substituted bridge)", "OpenScientist autonomous research run" ], "dismech_records": [ { "name": "germinal_center_reaction", "url": "https://dismech.monarchinitiative.org/pages/modules/germinal_center_reaction.html" }, { "name": "TDAR_AOP", "url": "https://dismech.monarchinitiative.org/pages/projects/TDAR_AOP.html" } ] }, "11905": { "number": 11905, "type": "pr", "title": "Correct what the TDAR AOP page says is outstanding, and close a stale open question", "url": "https://github.com/monarch-initiative/dismech/pull/11905", "state": "merged", "author": "gingin77", "created": "2026-09-15", "merged": "2026-09-17", "draft": false, "files_changed": [ "projects/TDAR_AOP.md" ], "labels": [], "gingin77_role": "author", "group": "tdar-aop", "why": "The page understated what was outstanding and implied uniform verification depth.", "achieved": "Named the six unchecked report sections, stated which sections were verified to abstract level, and recorded that AOP-side observations are not tracked as dismech work.", "blockers": "KER1510 and KER2027 weight-of-evidence never pulled; the report's limitations and proposed experiments untouched.", "methods": [], "dismech_records": [ { "name": "TDAR_AOP", "url": "https://dismech.monarchinitiative.org/pages/projects/TDAR_AOP.html" } ] }, "12003": { "number": 12003, "type": "pr", "title": "Separate the TDAR report's failed claims and its dismech actions into their own documents", "url": "https://github.com/monarch-initiative/dismech/pull/12003", "state": "merged", "author": "gingin77", "created": "2026-09-17", "merged": "2026-09-17", "draft": false, "files_changed": [ "projects/TDAR_AOP.md", "projects/TDAR_AOP/failed-claims.md", "projects/TDAR_AOP/findings-to-actions.md" ], "labels": [], "gingin77_role": "author", "group": "tdar-aop", "why": "Readers kept reconstructing which report claims failed and which findings imply dismech work.", "achieved": "failed-claims.md (five items) and findings-to-actions.md (twelve sections: five imply dismech work, seven are AOP-only).", "blockers": "Three of the report's seven evidence streams skip the TDAR node; the linkage it was commissioned to establish is the part that failed. Durable value: a module conformance audit (#11897) and one edge (#11907).", "methods": [], "dismech_records": [ { "name": "TDAR_AOP", "url": "https://dismech.monarchinitiative.org/pages/projects/TDAR_AOP.html" }, { "name": "germinal_center_reaction", "url": "https://dismech.monarchinitiative.org/pages/modules/germinal_center_reaction.html" } ] }, "12923": { "number": 12923, "type": "pr", "title": "Fetch and cache ToxCast assay-endpoint annotations", "url": "https://github.com/monarch-initiative/dismech/pull/12923", "state": "merged", "author": "gingin77", "created": "2026-09-26", "merged": "2026-09-26", "draft": false, "files_changed": [ ".claude/skills/epa-ctx-api/SKILL.md", ".gitignore", "data/toxcast/MANIFEST.yaml", "project.justfile", "src/dismech/toxcast_assays.py", "tests/data/toxcast/assay_annotations.json", "tests/test_toxcast_assays.py" ], "labels": [], "gingin77_role": "author", "group": "toxcast-assay-mapping", "why": "#12858's coverage deliverable was not computable because no ToxCast metadata existed on disk.", "achieved": "Fetch recipe into gitignored data/toxcast/, parsed AssayEndpoint objects, a committed MANIFEST with retrieval date, the skill, and 18 offline tests on a fixture.", "blockers": "Deliberately not a StructuredSource and no TOXCAST: prefix, so ToxCast remains non-citable. Reviewer caught the skill naming nonexistent recipes and cache rows; rewritten 323 to 177 lines. by-endpoint search needs a param named endpoint. Provenance is a date only.", "methods": [ "just toxcast-refresh fetch of ~1,570 ToxCast/Tox21 endpoint descriptions", "epa-ctx-api skill" ], "dismech_records": [ { "name": "TOXCAST", "url": "https://dismech.monarchinitiative.org/pages/projects/TOXCAST.html" } ], "supporting_files": [ { "path": "src/dismech/toxcast_assays.py", "url": "https://github.com/monarch-initiative/dismech/blob/main/src/dismech/toxcast_assays.py" }, { "path": ".claude/skills/epa-ctx-api/SKILL.md", "url": "https://github.com/monarch-initiative/dismech/blob/main/.claude/skills/epa-ctx-api/SKILL.md" } ] }, "13226": { "number": 13226, "type": "pr", "title": "Add projects/TOXCAST.md: ToxCast assay coverage of the pathograph by node, gene and disease", "url": "https://github.com/monarch-initiative/dismech/pull/13226", "state": "merged", "author": "gingin77", "created": "2026-09-30", "merged": "2026-09-30", "draft": false, "files_changed": [ ".claude/skills/epa-ctx-api/SKILL.md", "data/toxcast/MANIFEST.yaml", "docs/reports/toxcast-pathograph-coverage-2026-09-30.md", "mkdocs.yml", "project.justfile", "projects/TOXCAST.md", "scripts/toxcast_pathograph_coverage.py", "src/dismech/toxcast_assays.py", "tests/test_toxcast_assays.py", "tests/test_toxcast_pathograph_coverage.py" ], "labels": [], "gingin77_role": "author", "group": "toxcast-assay-mapping", "why": "Quantify how far ToxCast assay metadata reaches into the pathograph (deliverable 1 of #12858).", "achieved": "projects/TOXCAST.md, the script, a report and 23 tests: 552 of 1,570 endpoints share a gene with a node, reaching 452 of 22,403 nodes in 317 of 3,256 entries; nuclear receptors are the largest family.", "blockers": "These are candidates for a mapping, not mappings. organism names the assay system, not the gene's species; 71 candidates reach a node only through an ortholog. Gene-level species is an EPA-internal number with no published key. Three stale gene symbols rewritten. No join on the 462 gene-less endpoints or the 82 percent of nodes naming no gene. Reviewer could not re-run without an API key.", "methods": [ "ToxCast pathograph coverage script (just toxcast-coverage)" ], "dismech_records": [ { "name": "TOXCAST", "url": "https://dismech.monarchinitiative.org/pages/projects/TOXCAST.html" } ], "supporting_files": [ { "path": "scripts/toxcast_pathograph_coverage.py", "url": "https://github.com/monarch-initiative/dismech/blob/main/scripts/toxcast_pathograph_coverage.py" }, { "path": "docs/reports/toxcast-pathograph-coverage-2026-09-30.md", "url": "https://github.com/monarch-initiative/dismech/blob/main/docs/reports/toxcast-pathograph-coverage-2026-09-30.md" } ] }, "13228": { "number": 13228, "type": "pr", "title": "Add the THRB worked example to projects/TOXCAST.md", "url": "https://github.com/monarch-initiative/dismech/pull/13228", "state": "merged", "author": "gingin77", "created": "2026-09-30", "merged": "2026-09-30", "draft": false, "files_changed": [ "mkdocs.yml", "projects/TOXCAST.md", "references_cache/PMID_31566444.md", "scripts/toxcast_pathograph_coverage.py" ], "labels": [], "gingin77_role": "author", "group": "toxcast-assay-mapping", "why": "Show that writing one ToxCast assay into the existing model-to-mechanism vocabulary produces a record that validates cleanly and asserts something false.", "achieved": "A full ExperimentalModel plus ModelMechanismLink record on the project page against THRB Dominant-Negative Receptor Formation, with a MEASURES readout for the coactivator-recruitment emission ratio; cache for PMID:31566444. Nothing committed to kb/.", "blockers": "The gene join reaches the lesion node, not the state node, which names no gene; only 64 of 452 candidate nodes carry genetic_context. Both divergences come out INVALIDATING; no panel endpoint expresses a disease allele. ExperimentalModel has nothing to say about a cell-free assay. THRA and THRB share paralog-blind GH3 endpoints while the two entries exist to separate the paralogs.", "methods": [ "TOX21_TRB_COA_Antagonist_Followup_ratio cell-free TR-FRET coactivator recruitment assay" ], "dismech_records": [ { "name": "Generalized_Resistance_to_Thyroid_Hormone", "url": "https://dismech.monarchinitiative.org/pages/disorders/Generalized_Resistance_to_Thyroid_Hormone.html" }, { "name": "TOXCAST", "url": "https://dismech.monarchinitiative.org/pages/projects/TOXCAST.html" } ] }, "13236": { "number": 13236, "type": "pr", "title": "Pin the two THRB endpoints the ToxCast worked example rests on", "url": "https://github.com/monarch-initiative/dismech/pull/13236", "state": "merged", "author": "gingin77", "created": "2026-09-30", "merged": "2026-09-30", "draft": false, "files_changed": [ "tests/data/toxcast/assay_annotations.json", "tests/test_toxcast_assays.py", "tests/test_toxcast_pathograph_coverage.py" ], "labels": [], "gingin77_role": "author", "group": "toxcast-assay-mapping", "why": "The #13228 review could not verify per-endpoint annotations because the cache is gitignored and needs an API key.", "achieved": "Fixture grows from 7 to 9 endpoints with assertions pinning the two THRB endpoints' facts; 46 tests pass.", "blockers": "Other page claims remain key-only; pinning the whole panel is not the answer because the EPA API is unversioned. One overstatement in the PR body retracted after review.", "methods": [], "dismech_records": [ { "name": "TOXCAST", "url": "https://dismech.monarchinitiative.org/pages/projects/TOXCAST.html" } ] }, "13219": { "number": 13219, "type": "pr", "title": "Add an Endocrine Disruptor Screening History section to the estrogen project page", "url": "https://github.com/monarch-initiative/dismech/pull/13219", "state": "merged", "author": "gingin77", "created": "2026-09-30", "merged": "2026-09-30", "draft": false, "files_changed": [ "projects/ESTROGEN_SIGNALLING.md" ], "labels": [], "gingin77_role": "author", "group": "edsp-history", "why": "Give the page citation backing for its EDSP and ToxCast claims.", "achieved": "A new section with 17 PubMed-verified identifiers: the 1996 Food Quality Protection Act, three OECD guidelines plus the uterotrophic ring trial, the ToxCast ER model EPA accepted in place of three Tier 1 assays including an in vivo study, the AR model, CERAPP and CoMPARA, and AOP-Wiki counts.", "blockers": "The 40-endpoint ESR1 figure is computed, not published. None of the 26 estrogen AOPs carries OECD endorsement while AR, aromatase and thyroid AOPs do. AOP counts pin a snapshot date but not the CLI command. Reviewer could not reach the OECD guidelines or statute from its sandbox.", "methods": [ "EDSP Tier 1 screening history", "ToxCast ER and AR pathway models", "OECD TG 455, 493 and 440", "CERAPP and CoMPARA" ], "dismech_records": [ { "name": "ESTROGEN_SIGNALLING", "url": "https://dismech.monarchinitiative.org/pages/projects/ESTROGEN_SIGNALLING.html" } ] }, "13424": { "number": 13424, "type": "pr", "title": "Report DNT in vitro battery coverage of the pathograph", "url": "https://github.com/monarch-initiative/dismech/pull/13424", "state": "merged", "author": "gingin77", "created": "2026-10-03", "merged": "2026-10-03", "draft": false, "files_changed": [ "docs/reports/dnt-ivb-pathograph-coverage-2026-10-02.md", "mkdocs.yml", "project.justfile", "scripts/dnt_ivb_coverage.py", "tests/test_dnt_ivb_coverage.py" ], "labels": [], "gingin77_role": "author", "group": "dnt-ivb-coverage", "why": "Measure what the developmental neurotoxicity in vitro battery's endpoints reach in dismech.", "achieved": "Script, report with 1,157 distinct links and 14 tests. Escape response, anxiety-like behaviour and epigenetic markers reach no node with a model; learning and memory reaches one in 242; neural network formation looks covered but most matched nodes describe hyperexcitability in epilepsies; one organ-on-chip in the matched set.", "blockers": "Lexical matching, not a mapping: every count is an upper bound. Three filter mistakes documented (cognit matching recognition receptors; the neural filter dropping the most on-point node; bare progenitor admitting hematopoietic nodes). Page anchors fail silently on renamed duplicates.", "methods": [ "DNT in vitro battery (Tal et al. 2024, 17 processes)", "coverage script (just dnt-ivb-coverage)" ], "dismech_records": [], "supporting_files": [ { "path": "scripts/dnt_ivb_coverage.py", "url": "https://github.com/monarch-initiative/dismech/blob/main/scripts/dnt_ivb_coverage.py" }, { "path": "docs/reports/dnt-ivb-pathograph-coverage-2026-10-02.md", "url": "https://github.com/monarch-initiative/dismech/blob/main/docs/reports/dnt-ivb-pathograph-coverage-2026-10-02.md" } ] }, "13451": { "number": 13451, "type": "pr", "title": "Add chlorpyrifos zebrafish VAMR behaviour model to Organophosphate_Poisoning", "url": "https://github.com/monarch-initiative/dismech/pull/13451", "state": "merged", "author": "gingin77", "created": "2026-10-03", "merged": "2026-10-03", "draft": false, "files_changed": [ "history/disorders/Organophosphate_Poisoning/2026-10-03T153612Z-claude-code-853b9a.yaml", "history/disorders/Organophosphate_Poisoning/2026-10-03T162116Z-claude-code-3fecf2.yaml", "kb/disorders/Organophosphate_Poisoning.yaml", "references_cache/PMID_41780647.md", "references_cache/url_https___zenodo.org_records_23035979_files_1-s2.0-S0161813X26000355-main.pdf.md" ], "labels": [], "gingin77_role": "author", "group": "zebrafish-vamr", "why": "Step 1 of #13450; Organophosphate_Poisoning had no animal or experimental model at all.", "achieved": "First animal_models entry on the disorder: zebrafish larvae attached to Central cholinergic overstimulation as PERTURBS with PROXY_QUANTITY and SPECIES_MISMATCH divergences and four readouts across the acute and developmental arms; two reference caches, 65/65 snippets.", "blockers": "Scope gate: a PR touching kb/ may not touch docs/, so the report moved to #13452. Reviewer overturned MEASURES for PERTURBS. Both AC50 explanations originally implied all 26 endpoints while the most sensitive acute endpoint sits fivefold below the quoted floor. CHANGES_REQUESTED because the history record still described the old state; resolved by appending a second REVIEW record.", "methods": [ "chlorpyrifos zebrafish VAMR animal model" ], "dismech_records": [ { "name": "Organophosphate_Poisoning", "url": "https://dismech.monarchinitiative.org/pages/disorders/Organophosphate_Poisoning.html" } ] }, "13452": { "number": 13452, "type": "pr", "title": "Add a report on the zebrafish VAMR behaviour assay", "url": "https://github.com/monarch-initiative/dismech/pull/13452", "state": "merged", "author": "gingin77", "created": "2026-10-03", "merged": "2026-10-03", "draft": false, "files_changed": [ "docs/reports/data/vamr-endpoint-hit-calls-2026-10-03.tsv", "docs/reports/zebrafish-vamr-assay-2026-10-03.md", "mkdocs.yml", "scripts/vamr_endpoint_hit_calls.py" ], "labels": [], "gingin77_role": "author", "group": "zebrafish-vamr", "why": "Carry the assay documentation and per-endpoint data without a kb/ change.", "achieved": "Report, a TSV of all 884 concentration-response fits with a passes_hit_rule column, and a script whose --check mode reproduces the TSV byte for byte; reviewer recomputed with zero mismatches.", "blockers": "Applying the paper's own hit rule does not reproduce all its reported results (four disagreements, including the habituation effects attributed to ketamine, nicotine and trichlorfon). Four rounds of CHANGES_REQUESTED on presentation. The workbook stays out of the repo because the supplement's licence is unstated. openpyxl imported undeclared.", "methods": [ "VAMR hit-call re-derivation script (scripts/vamr_endpoint_hit_calls.py)" ], "dismech_records": [], "supporting_files": [ { "path": "docs/reports/zebrafish-vamr-assay-2026-10-03.md", "url": "https://github.com/monarch-initiative/dismech/blob/main/docs/reports/zebrafish-vamr-assay-2026-10-03.md" }, { "path": "docs/reports/data/vamr-endpoint-hit-calls-2026-10-03.tsv", "url": "https://github.com/monarch-initiative/dismech/blob/main/docs/reports/data/vamr-endpoint-hit-calls-2026-10-03.tsv" }, { "path": "scripts/vamr_endpoint_hit_calls.py", "url": "https://github.com/monarch-initiative/dismech/blob/main/scripts/vamr_endpoint_hit_calls.py" } ] }, "13463": { "number": 13463, "type": "pr", "title": "Feasibility report: a ToxAssayMech built with mechmaker", "url": "https://github.com/monarch-initiative/dismech/pull/13463", "state": "merged", "author": "app/ai4c-agent", "created": "2026-10-03", "merged": "2026-10-06", "draft": false, "files_changed": [ "docs/reports/toxassaymech-feasibility-2026-10-03.md", "mkdocs.yml" ], "labels": [], "gingin77_role": "related (authored by ai4c-agent at cmungall's request on #13452)", "group": "zebrafish-vamr", "why": "cmungall asked for a report on building a ToxAssayMech with the mechmaker framework after three efforts (ToxCast, DNT-IVB, VAMR) each improvised a home for assay-battery data.", "achieved": "Feasibility report: mechmaker is sufficient; SOMAMech already exists in overlapping territory and must be consulted first; AOP-Wiki KEs are the obvious skeleton but 65 percent of KERs carry no references.", "blockers": "One blocking review item on the THRA/THRB example, fixed; merged by the shepherd.", "methods": [ "ToxAssayMech feasibility (mechmaker)" ], "dismech_records": [], "supporting_files": [ { "path": "docs/reports/toxassaymech-feasibility-2026-10-03.md", "url": "https://github.com/monarch-initiative/dismech/blob/main/docs/reports/toxassaymech-feasibility-2026-10-03.md" } ] }, "13755": { "number": 13755, "type": "pr", "title": "MDD: qualify the SSRI reuptake-inhibition mechanism with C. elegans pharmacology (#13749)", "url": "https://github.com/monarch-initiative/dismech/pull/13755", "state": "merged", "author": "gingin77", "created": "2026-10-09", "merged": "2026-10-09", "draft": false, "files_changed": [ "history/disorders/Major_Depressive_Disorder/2026-10-09T141316Z-claude-code-5e7373.yaml", "history/disorders/Major_Depressive_Disorder/2026-10-09T144208Z-claude-code-2d5c59.yaml", "kb/disorders/Major_Depressive_Disorder.yaml", "references_cache/PMID_11487610.md", "references_cache/PMID_15121647.md", "references_cache/PMID_15654117.md", "references_cache/PMID_20739712.md" ], "labels": [], "gingin77_role": "author", "group": "celegans-mdd-models", "why": "The SSRI link to Monoamine Deficiency said SSRIs work by blocking presynaptic reuptake; three nematode genetic studies show reuptake inhibition is primary but not sufficient.", "achieved": "Rewrote the link description to keep reuptake inhibition primary and add the receptor-level actions, ending with the statement that their human contribution is not established; five MODEL_ORGANISM, INDIRECT evidence items; 112/112 snippets.", "blockers": "None blocking; reviewer approved and noted the worm findings name fluoxetine rather than SSRIs as a class.", "methods": [ "C. elegans fluoxetine pharmacology: transporter-independent action, SER-7 binding, SERT-dependent and -independent responses" ], "dismech_records": [ { "name": "Major_Depressive_Disorder", "url": "https://dismech.monarchinitiative.org/pages/disorders/Major_Depressive_Disorder.html" } ] }, "13756": { "number": 13756, "type": "pr", "title": "MDD: add tph-1 and daf-2 C. elegans animal models (#13749)", "url": "https://github.com/monarch-initiative/dismech/pull/13756", "state": "merged", "author": "gingin77", "created": "2026-10-09", "merged": "2026-10-09", "draft": false, "files_changed": [ "history/disorders/Major_Depressive_Disorder/2026-10-09T141904Z-claude-code-ff56d2.yaml", "kb/disorders/Major_Depressive_Disorder.yaml", "references_cache/PMID_10676966.md", "references_cache/PMID_17141627.md", "references_cache/PMID_29230398.md", "references_cache/PMID_41986315.md" ], "labels": [], "gingin77_role": "author", "group": "celegans-mdd-models", "why": "Add the two Tier 1 models from #13749 as the entry's first animal_models section.", "achieved": "tph-1 linked to Monoamine Deficiency and daf-2 to Reference Point Dysregulation, both PARTIALLY_RECAPITULATES at LOW fidelity with SPECIES_MISMATCH, PROXY_QUANTITY and CONTESTED_ASSUMPTION divergences; genes carry human orthologs TPH2 and INSR with alternatives in notes; 116/116 snippets.", "blockers": "Two CHANGES_REQUESTED rounds: the daf-2 notes cited the wrong paper, and the tph-1 note pointed at citations only present on the sibling PR. The DAF-16/FOXO dependency was noted but not made a node pending the OpenScientist run.", "methods": [ "tph-1 serotonin-null C. elegans animal model", "daf-2 insulin-receptor immobility C. elegans animal model" ], "dismech_records": [ { "name": "Major_Depressive_Disorder", "url": "https://dismech.monarchinitiative.org/pages/disorders/Major_Depressive_Disorder.html" } ] }, "13757": { "number": 13757, "type": "pr", "title": "MDD: record the C. elegans risk-gene panels as a knowledge gap, not as models (#13749)", "url": "https://github.com/monarch-initiative/dismech/pull/13757", "state": "merged", "author": "gingin77", "created": "2026-10-09", "merged": "2026-10-09", "draft": false, "files_changed": [ "history/disorders/Major_Depressive_Disorder/2026-10-09T142242Z-claude-code-c5ebcc.yaml", "history/disorders/Major_Depressive_Disorder/2026-10-09T143536Z-claude-code-c567d1.yaml", "kb/disorders/Major_Depressive_Disorder.yaml", "references_cache/PMID_34335334.md", "references_cache/PMID_38362034.md", "references_cache/PMID_41986315.md" ], "labels": [], "gingin77_role": "author", "group": "celegans-mdd-models", "why": "The issue proposed the worm risk-gene panels as animal models; on reading, they are a conservation analysis plus two suicidality-gene panels with no human anchor in the entry.", "achieved": "A KNOWLEDGE_GAP discussion attached to the serotonin genes and Reference Point Dysregulation, grading the conservation result COMPUTATIONAL and the immobility results MODEL_ORGANISM, with a footnote that lithium worsened four strains and one proposed experiment on mod-5, ser-1 and ser-4.", "blockers": "CHANGES_REQUESTED: ser-4 is a 5-HT1-like receptor, not HTR2A-family; the rationale pointed at a daf-2 model the branch did not yet contain; a missing experiment_id failed CI; strain counts corrected.", "methods": [ "risk-gene mutant panel foraging-immobility assay recorded as a KNOWLEDGE_GAP discussion" ], "dismech_records": [ { "name": "Major_Depressive_Disorder", "url": "https://dismech.monarchinitiative.org/pages/disorders/Major_Depressive_Disorder.html" } ] }, "13759": { "number": 13759, "type": "pr", "title": "MDD: resolve the serotonin-to-FOXO arm as a human-model mismatch after an OpenScientist run (#13749)", "url": "https://github.com/monarch-initiative/dismech/pull/13759", "state": "merged", "author": "gingin77", "created": "2026-10-09", "merged": "2026-10-09", "draft": false, "files_changed": [ "history/disorders/Major_Depressive_Disorder/2026-10-09T144856Z-claude-code-8a90c7.yaml", "kb/disorders/Major_Depressive_Disorder.yaml", "kb/hypotheses/Major_Depressive_Disorder/serotonin_foxo_stress_transcription_model/assessments/openscientist-assessment-by-claude-fable-5-1.yaml", "kb/hypotheses/Major_Depressive_Disorder/serotonin_foxo_stress_transcription_model/openscientist.md", "kb/hypotheses/Major_Depressive_Disorder/serotonin_foxo_stress_transcription_model/openscientist.md.citations.md", "kb/hypotheses/Major_Depressive_Disorder/serotonin_foxo_stress_transcription_model/openscientist_artifacts/final_report.html", "kb/hypotheses/Major_Depressive_Disorder/serotonin_foxo_stress_transcription_model/openscientist_artifacts/final_report.pdf", "kb/hypotheses/Major_Depressive_Disorder/serotonin_foxo_stress_transcription_model/openscientist_artifacts/kb_hypotheses_Major_Depressive_Disorder_serotonin_foxo_stress_transcription_model_openscientist_artifacts_data_foxo1_mdd_crediblesets.json", "kb/hypotheses/Major_Depressive_Disorder/serotonin_foxo_stress_transcription_model/openscientist_artifacts/kb_hypotheses_Major_Depressive_Disorder_serotonin_foxo_stress_transcription_model_openscientist_artifacts_data_mdd_top_targets_context.csv", "kb/hypotheses/Major_Depressive_Disorder/serotonin_foxo_stress_transcription_model/openscientist_artifacts/kb_hypotheses_Major_Depressive_Disorder_serotonin_foxo_stress_transcription_model_openscientist_artifacts_data_opentargets_foxo_mdd_associations.csv", "kb/hypotheses/Major_Depressive_Disorder/serotonin_foxo_stress_transcription_model/openscientist_artifacts/kb_hypotheses_Major_Depressive_Disorder_serotonin_foxo_stress_transcription_model_openscientist_artifacts_data_opentargets_foxo_mdd_associations.json", "kb/hypotheses/Major_Depressive_Disorder/serotonin_foxo_stress_transcription_model/openscientist_artifacts/kb_hypotheses_Major_Depressive_Disorder_serotonin_foxo_stress_transcription_model_openscientist_artifacts_logs_search_log.md", "references_cache/PMID_15541711.md", "references_cache/PMID_21732403.md", "references_cache/PMID_28088287.md", "references_cache/PMID_34782712.md", "references_cache/PMID_35854107.md", "references_cache/PMID_36039087.md", "references_cache/PMID_36356194.md", "references_cache/PMID_36819781.md", "references_cache/PMID_37173696.md", "references_cache/PMID_40237232.md", "references_cache/PMID_41249439.md", "references_cache/PMID_41555281.md", "references_cache/PMID_41622191.md", "references_cache/PMID_41780463.md", "references_cache/PMID_42538881.md", "references_cache/PMID_42632434.md" ], "labels": [], "gingin77_role": "author", "group": "celegans-mdd-models", "why": "Settle whether the DAF-16/FOXO dependency seen in worm serotonin and antidepressant work justifies a new insulin/FOXO pathophysiology node.", "achieved": "Registered serotonin_foxo_stress_transcription_model as an EMERGING hypothesis, ran it through OpenScientist (19 citations, all resolved), assessed it WEAKLY_SUPPORTED_UNRESOLVED, and recorded a HUMAN_MODEL_MISMATCH discussion with three proposed experiments plus a worm lithium evidence item on Lithium Augmentation; 125/125 snippets.", "blockers": "The chain holds only in the worm; rodents give an AKT-to-FOXO arm but no serotonin-to-FOXO test; the one human cohort is null; the only human genetic signal is a FOXO1 interaction locus. Provider analyses marked PARTIAL because the bundle lacks its query file and MANIFEST. One evidence snippet did not contain the FOXO1 claim and was replaced.", "methods": [ "OpenScientist hypothesis deep-research run with assessment sidecar", "Open Targets FOXO-MDD association replay", "HUMAN_MODEL_MISMATCH discussion" ], "dismech_records": [ { "name": "Major_Depressive_Disorder", "url": "https://dismech.monarchinitiative.org/pages/disorders/Major_Depressive_Disorder.html" } ], "supporting_files": [ { "path": "kb/hypotheses/Major_Depressive_Disorder/serotonin_foxo_stress_transcription_model/openscientist.md", "url": "https://github.com/monarch-initiative/dismech/blob/main/kb/hypotheses/Major_Depressive_Disorder/serotonin_foxo_stress_transcription_model/openscientist.md" } ] }, "13776": { "number": 13776, "type": "pr", "title": "MDD: link the tph-1 model from the risk-gene gap and cite the forced-swim validity dispute (#13749)", "url": "https://github.com/monarch-initiative/dismech/pull/13776", "state": "merged", "author": "gingin77", "created": "2026-10-09", "merged": "2026-10-09", "draft": false, "files_changed": [ "history/disorders/Major_Depressive_Disorder/2026-10-09T180636Z-claude-code-4a63c9.yaml", "kb/disorders/Major_Depressive_Disorder.yaml", "references_cache/PMID_26386543.md", "references_cache/PMID_28287253.md" ], "labels": [], "gingin77_role": "author", "group": "celegans-mdd-models", "why": "Close two loose ends: the risk-gene gap's notes asked to link a tph-1 model once one existed, and the CONTESTED_ASSUMPTION divergence on daf-2 cited no source for the forced-swim dispute.", "achieved": "attaches_to gains the tph-1 model; two REVIEW_SYNTHESIS items (Molendijk and de Kloet 2015, Commons 2017) added; 149/149 snippets.", "blockers": "None; approved on first review.", "methods": [ "forced-swim test validity critique cited as REVIEW_SYNTHESIS" ], "dismech_records": [ { "name": "Major_Depressive_Disorder", "url": "https://dismech.monarchinitiative.org/pages/disorders/Major_Depressive_Disorder.html" } ] }, "13788": { "number": 13788, "type": "pr", "title": "Bipolar Disorder: list the patient iPSC neuron model as an experimental model (#13600)", "url": "https://github.com/monarch-initiative/dismech/pull/13788", "state": "merged", "author": "gingin77", "created": "2026-10-09", "merged": "2026-10-10", "draft": false, "files_changed": [ "history/disorders/Bipolar_Disorder/2026-10-09T193053Z-claude-code-ed8b21.yaml", "kb/disorders/Bipolar_Disorder.yaml" ], "labels": [], "gingin77_role": "author", "group": "lithium-npc-model", "why": "The Mertens 2015 study was cited inside two pathophysiology nodes but never listed as a model; this is decision 3 of #13600, split out of #13603 so it does not wait on #13602.", "achieved": "The entry's first and only patient-derived experimental model: RECAPITULATES on Neuronal Hyperexcitability at MODERATE fidelity with a lithium-responder readout and three typed divergences, MEASURES on Mitochondrial Dysfunction because the paper reports enhanced function.", "blockers": "Fidelity capped at MODERATE because the finding has not been matched to measurements in patients' brains; six white male donors.", "methods": [ "patient iPSC-derived hippocampal dentate gyrus-like neurons from six bipolar I patients and four controls (Mertens 2015)" ], "dismech_records": [ { "name": "Bipolar_Disorder", "url": "https://dismech.monarchinitiative.org/pages/disorders/Bipolar_Disorder.html" } ] }, "13603": { "number": 13603, "type": "pr", "title": "Bipolar Disorder: add the lithium-exposed neural progenitor model (draft, held for #13602)", "url": "https://github.com/monarch-initiative/dismech/pull/13603", "state": "open", "author": "gingin77", "created": "2026-10-05", "merged": null, "draft": true, "files_changed": [ "cache/enums/anatomicalentityterm_c7eab8227a65.csv", "cache/uberon/terms.csv", "history/disorders/Bipolar_Disorder/2026-10-05T170806Z-claude-code-0ebca2.yaml", "kb/disorders/Bipolar_Disorder.yaml", "references_cache/PMID_36307327.md" ], "labels": [], "gingin77_role": "author", "group": "lithium-npc-model", "why": "Preserve checked evidence while the scope question is settled.", "achieved": "Unmerged draft, narrowed after #13788 took the iPSC neuron model: the lithium-exposed progenitor model to Neuroplasticity Alterations (PERTURBS, four typed divergences, one INVALIDATING) and to GSK-3beta signalling (MEASURES); 112/112 snippets, 7,467 tests pass.", "blockers": "Reviewer CHANGES_REQUESTED: about 30 new evidence items lack reference_title; one quote should be BACKGROUND. Suggestions: COMPUTATIONAL for heritability lookups; split model 2; the GSK-3beta link can be dropped. Model 1 waits on the maintainer decision in #13602.", "methods": [ "primary human fetal cortical neural progenitors from 83 genotyped unaffected donors exposed to LiCl for 48 h (Wolter 2023, Valone 2026)" ], "dismech_records": [ { "name": "Bipolar_Disorder", "url": "https://dismech.monarchinitiative.org/pages/disorders/Bipolar_Disorder.html" } ] }, "13787": { "number": 13787, "type": "pr", "title": "Add a report on the valproic acid and lithium GxT paper, and what it exposed about model curation", "url": "https://github.com/monarch-initiative/dismech/pull/13787", "state": "merged", "author": "gingin77", "created": "2026-10-09", "merged": "2026-10-09", "draft": false, "files_changed": [ "docs/reports/vpa-lithium-gxt-paper-dismech-fit-2026-10-05.md", "mkdocs.yml" ], "labels": [], "gingin77_role": "author", "group": "vpa-lithium-gxt-report", "why": "Ask what a single 2026 Molecular Psychiatry paper could add to dismech, and record what became of each gap.", "achieved": "A report under docs/reports naming five entry gaps (four became work: #13604, #13779, #13600, #13778) and three schema limits: no structured exposure dose, no genotyped donor panel, no gene-by-exposure interaction. The fetal valproate syndrome entry recorded the panel and exposure as prose and dropped the response QTL result.", "blockers": "The 21 supplementary tables were not read; two knowledge-base claims went stale and were corrected; one line claiming no gap was filed was wrong, corrected by #13794.", "methods": [ "response QTL mapping in lithium- and valproate-exposed genotyped human neural progenitors (Valone 2026)" ], "dismech_records": [ { "name": "Bipolar_Disorder", "url": "https://dismech.monarchinitiative.org/pages/disorders/Bipolar_Disorder.html" } ], "supporting_files": [ { "path": "docs/reports/vpa-lithium-gxt-paper-dismech-fit-2026-10-05.md", "url": "https://github.com/monarch-initiative/dismech/blob/main/docs/reports/vpa-lithium-gxt-paper-dismech-fit-2026-10-05.md" } ] }, "13794": { "number": 13794, "type": "pr", "title": "Correct what the VPA GxT report says about the issue tracker", "url": "https://github.com/monarch-initiative/dismech/pull/13794", "state": "merged", "author": "gingin77", "created": "2026-10-09", "merged": "2026-10-12", "draft": false, "files_changed": [ "docs/reports/vpa-lithium-gxt-paper-dismech-fit-2026-10-05.md" ], "labels": [], "gingin77_role": "author", "group": "vpa-lithium-gxt-report", "why": "The report said none of its three schema gaps were filed; #13768 had been opened three hours before it merged and covers the first row.", "achieved": "Corrected paragraph: the perturbation gap is #13768; the donor-population gap is recorded in #13602 with no issue asking for a change; a tracker search found nothing for the gene-by-exposure row, and whether that row belongs in dismech is open since a response QTL describes variance across a donor panel, with EnviroMech or a pharmacogenomic Mech as candidate homes.", "blockers": "Docs only; two review rounds on hedging and on linking EnviroMech as a separate project; rebased once before merge.", "methods": [], "dismech_records": [], "supporting_files": [ { "path": "docs/reports/vpa-lithium-gxt-paper-dismech-fit-2026-10-05.md", "url": "https://github.com/monarch-initiative/dismech/blob/main/docs/reports/vpa-lithium-gxt-paper-dismech-fit-2026-10-05.md" } ] }, "13548": { "number": 13548, "type": "pr", "title": "Admit NCBIGene and UniProtKB on animal and experimental model genes (#13120)", "url": "https://github.com/monarch-initiative/dismech/pull/13548", "state": "open", "author": "caufieldjh", "created": "2026-10-04", "merged": null, "draft": false, "files_changed": [ ".github/workflows/main.yaml", "CLAUDE.md", "cache/ncbigene/terms.csv", "cache/uniprotkb/terms.csv", "conf/oak_config.yaml", "docs/explanation/design-decisions.md", "history/disorders/Autosomal_Dominant_Nonsyndromic_Hearing_Loss_9/2026-10-09T163921Z-claude-code-5ea24a.yaml", "history/disorders/Severe_Combined_Immunodeficiency_Due_To_CORO1A_Deficiency/2026-10-09T163921Z-claude-code-4dce55.yaml", "history/disorders/TMEM165-Congenital_Disorder_of_Glycosylation/2026-10-09T163921Z-claude-code-f28e5e.yaml", "history/schema/GeneOrProductDescriptor/2026-10-09T163920Z-claude-code-2edd6e.yaml", "kb/disorders/Autosomal_Dominant_Nonsyndromic_Hearing_Loss_9.yaml", "kb/disorders/Severe_Combined_Immunodeficiency_Due_To_CORO1A_Deficiency.yaml", "kb/disorders/TMEM165-Congenital_Disorder_of_Glycosylation.yaml", "project.justfile", "scripts/check_gene_namespaces.py", "src/dismech/schema/dismech.yaml", "src/dismech/templates/_model_cards.html.j2", "src/dismech/term_tooltips.py", "tests/test_gene_namespaces.py" ], "labels": [ "scope-override" ], "gingin77_role": "commented (authored by caufieldjh)", "group": "model-gene-namespaces", "why": "HGNC names only human genes, so a Coch knock-in mouse was bound to the human gene and a zebrafish morphant had no identifier at all.", "achieved": "Open, awaiting maintainer sign-off. Adds GeneOrProductDescriptor accepting hgnc, NCBIGene and UniProtKB on model genes, a new experimental_models.genes slot, an offline label check against a cached NCBI table, and three worked entries. gingin77 commented that the organism and perturbation half set aside here is tracked as #13768.", "blockers": "Narrowed from an earlier design that put model_system and perturbations on EvidenceItem. NCBIGene cannot be validated through OAK; eight MGI bindings are UNCHECKED_PREFIX; the gene index keys on HGNC so a mouse model drops off the human gene page until a structured orthology link exists.", "methods": [ "NCBIGene and UniProtKB identifiers on animal_models and experimental_models genes", "check-gene-namespaces offline gate" ], "dismech_records": [] }, "10513": { "number": 10513, "type": "pr", "title": "Add Bgee cross-species model fidelity check and integration proposal", "url": "https://github.com/monarch-initiative/dismech/pull/10513", "state": "merged", "author": "mellybelly", "created": "2026-09-02", "merged": "2026-09-26", "draft": false, "files_changed": [ "docs/bgee-integration-proposal.md", "docs/reports/scfair-dismech-schema-comparison-2026-09-02.md", "mkdocs.yml", "scripts/bgee_model_fidelity.py" ], "labels": [], "gingin77_role": "commented (authored by mellybelly)", "group": "bgee-fidelity", "why": "Check whether a model organism's ortholog of a disease gene is expressed in the anatomy where the human mechanism operates, a necessary but never sufficient condition for fidelity, and explain why Bgee presence calls cannot be imported as evidence.", "achieved": "Prototype script with DIVERGENT_ABSENT, ORTHOLOG_NOT_1TO1 and CONSERVED verdicts, resumable cache, 30+ species; integration proposal with three uses and questions for the Bgee team. gingin77's comment endorsed building the check, framing it as context of use: a NAM is chosen to match its context, and a model for advancing understanding of a complex disease differs from the minimal model for chemical safety screening.", "blockers": "79 percent of 260 links not evaluable due to anatomy mismatch; 4 percent cell-type coverage; Ensembl returned empty ortholog lists for PTEN and VHL; zero absent-call verdicts raise a question for Bgee.", "methods": [ "Bgee cross-species expression-based model fidelity check (scripts/bgee_model_fidelity.py)" ], "dismech_records": [], "supporting_files": [ { "path": "scripts/bgee_model_fidelity.py", "url": "https://github.com/monarch-initiative/dismech/blob/main/scripts/bgee_model_fidelity.py" }, { "path": "docs/bgee-integration-proposal.md", "url": "https://github.com/monarch-initiative/dismech/blob/main/docs/bgee-integration-proposal.md" } ] }, "10350": { "number": 10350, "type": "pr", "title": "fix: Regrade two inverted readout evidence items on the Ganab mouse (PKD3)", "url": "https://github.com/monarch-initiative/dismech/pull/10350", "state": "merged", "author": "gingin77", "created": "2026-09-01", "merged": "2026-09-04", "draft": false, "files_changed": [ "history/disorders/Polycystic_Kidney_Disease_3/2026-09-01T070852Z-claude-code-bdab93.yaml", "kb/disorders/Polycystic_Kidney_Disease_3.yaml" ], "labels": [], "gingin77_role": "author", "group": "ganab-readout-grading", "why": "Two evidence items on the mouse's FAILS_TO_RECAPITULATE link were graded REFUTE where the quoted sentence is the null observation the readout reports.", "achieved": "Both regraded to SUPPORT with DIRECT directness; the negative sense is carried by the relationship and the UNCHANGED direction. The third REFUTE on the HUMAN_MODEL_MISMATCH discussion was deliberately left. 31/31 snippets.", "blockers": "Nothing gates this error class because check-snippet-grading deliberately does not gate supports. Reviewer found 14 occurrences of the same shape across 12 other files. CLAUDE.md under-specifies what a discussions[] item's evidence is graded against. Merge blocked for days by the shepherd's stale-base check.", "methods": [ "Ganab+/- mouse FAILS_TO_RECAPITULATE readout grading" ], "dismech_records": [ { "name": "Polycystic_Kidney_Disease_3", "url": "https://dismech.monarchinitiative.org/pages/disorders/Polycystic_Kidney_Disease_3.html" } ] } }, "recurring_blockers": [ { "blocker": "No disease-agnostic assay record: experimental_models lives on Disease and a link must target a node in the same file, so a reusable endpoint is copied per disease with no shared identity.", "items": [ 12858, 13225, 13450, 13602 ] }, { "blocker": "The assays slot is bound to OBI with no OAK adapter or enum cache, and ECO is absent, so how a claim was measured cannot be recorded structurally.", "items": [ 10772, 11394, 12682, 9421 ] }, { "blocker": "Several of the primary papers behind the models curated here (the NSCLC organ-chip, the Akura Twin liver MPS, the ToxCast sizing paper and the zebrafish VAMR assay) were available only as abstracts or behind a paywall. Because dismech evidence must quote the cached reference, the quotable text in those cases ran out before the model's readouts were all covered.", "items": [ 9792, 9935, 12682, 13450 ] }, { "blocker": "Models involving co-cultures, gravity-linked plates and ex vivo slices, revealed some NAMO vocabulary gaps. Specifically, NAMO has no class for a non-perfused, gravity-linked microphysiological plate (its MPS class is abstract and requires microfluidics) or for ex vivo tissue slices, and the project page's in-scope list showed only four of NAMO's 56 classes, so one model was first left unbound for the wrong reason.", "items": [ 9935, 9997 ] }, { "blocker": "AnimalModel binds no organism and has no perturbation slot, so procedure-based and exposure-based whole-organism models have nowhere structured to say what was done to them.", "items": [ 13768, 13754, 13450, 13774 ] }, { "blocker": "Worm-to-human and fish-to-human gene orthology is one-to-many, and the human-ortholog convention on model genes forces a pick the biology does not support.", "items": [ 11140, 13548, 13749 ] }, { "blocker": "No structured exposure, dose, duration, kinetic series, donor population or gene-by-exposure interaction on a model.", "items": [ 13225, 13602, 13600, 13787 ] } ], "aop_inventory": { "document": "data/aop-framework-inventory-2026-10-13.md", "landed_methods": [ { "method": "AOP chain census script", "files": [ { "path": "scripts/aop_chain_census.py", "url": "https://github.com/monarch-initiative/dismech/blob/main/scripts/aop_chain_census.py" } ], "prs": [ 11852 ] }, { "method": "AOP-Wiki, MIE-KER-capture, KER-evidence-triage skills", "files": [ { "path": ".claude/skills/aop-wiki/SKILL.md", "url": "https://github.com/monarch-initiative/dismech/blob/main/.claude/skills/aop-wiki/SKILL.md" }, { "path": ".claude/skills/mie-ker-capture/SKILL.md", "url": "https://github.com/monarch-initiative/dismech/blob/main/.claude/skills/mie-ker-capture/SKILL.md" }, { "path": ".claude/skills/ker-evidence-triage/SKILL.md", "url": "https://github.com/monarch-initiative/dismech/blob/main/.claude/skills/ker-evidence-triage/SKILL.md" } ], "prs": [ 10464 ] } ], "recurring_blockers": [ { "blocker": "Exposures land on toxicokinetic nodes, never on a molecular initiating event, and nothing marks a node toxicokinetic.", "items": [ 10344, 11852 ] } ] }, "landed_in_kb": [ { "method": "Human orthotopic NSCLC lung organ-chip, TKI readout grounded in GO", "records": [ "Non-Small_Cell_Lung_Cancer" ], "items": [ 9931, 9665 ] }, { "method": "ESCC patient-derived organoid library", "records": [ "Esophageal_Squamous_Cell_Carcinoma" ], "items": [ 9797 ] }, { "method": "Akura Twin 384-well liver fibrosis MPS (co-culture)", "records": [ "Liver_Cirrhosis", "drug_induced_liver_injury" ], "items": [ 9935 ] }, { "method": "Scar-in-a-Jar macromolecular crowding fibroblast assay", "records": [ "fibrotic_response" ], "items": [ 10282 ] }, { "method": "Retinal organoid, iPSC-RPE, cortical organoid, iPSC-cardiomyocytes, ALI colonoid, cytokine-conditioned colon organoid, colon-on-chip (links added)", "records": [ "Stargardt_Disease", "Noonan_Syndrome", "Ulcerative_Colitis" ], "items": [ 10432, 10573 ] }, { "method": "ATP7B iPSC hepatocytes and prime-edited liver organoids; CEP290 optic cups and QR-110 retinal organoids; TSC2 cortical spheroids and cerebral organoids; BRAF V600E PDO/PDOX biobank; organoid-lymphocyte co-culture; BBSome RP animal models (links added)", "records": [ "Wilsons_Disease", "Leber_Congenital_Amaurosis_10", "Tuberous_Sclerosis_Complex", "BRAF_V600E_Mutant_Colorectal_Cancer", "MSI_High_Colorectal_Cancer", "BBSome-Related_Retinitis_Pigmentosa" ], "items": [ 12582 ] }, { "method": "tph-1 serotonin-null and daf-2 insulin-receptor C. elegans animal models; SSRI mechanism qualified with worm fluoxetine pharmacology; serotonin-to-FOXO hypothesis with HUMAN_MODEL_MISMATCH record", "records": [ "Major_Depressive_Disorder" ], "items": [ 13755, 13756, 13759, 13776 ] }, { "method": "Patient iPSC-derived dentate gyrus-like neurons with lithium-responder readout", "records": [ "Bipolar_Disorder" ], "items": [ 13788 ] }, { "method": "Chlorpyrifos zebrafish VAMR behaviour animal model", "records": [ "Organophosphate_Poisoning" ], "items": [ 13451 ] } ], "tooling": [ { "tool": "ToxCast/Tox21 endpoint annotation fetch and parser, just toxcast-refresh", "files": [ "toxcast_assays.py" ], "items": [ 12923 ] }, { "tool": "epa-ctx-api skill for the EPA CompTox API", "files": [ "SKILL.md" ], "items": [ 12923 ] }, { "tool": "ToxCast pathograph coverage script and report, just toxcast-coverage", "files": [ "toxcast_pathograph_coverage.py", "report", "projects/TOXCAST.md" ], "items": [ 13226, 13228, 13236 ] }, { "tool": "DNT in vitro battery coverage script and report, just dnt-ivb-coverage", "files": [ "dnt_ivb_coverage.py", "report" ], "items": [ 13424 ] }, { "tool": "VAMR hit-call re-derivation script, TSV of 884 fits, and assay report", "files": [ "vamr_endpoint_hit_calls.py", "TSV", "report" ], "items": [ 13452 ] }, { "tool": "Bgee cross-species model fidelity check (prototype, authored by another contributor; commented)", "files": [ "bgee_model_fidelity.py", "proposal" ], "items": [ 10513 ] }, { "tool": "Valproate and lithium gene-by-treatment fit report", "files": [ "report" ], "items": [ 13787, 13794 ] } ], "not_incorporated": [ { "method": "Virtual imaging trials (Duke CVIT) and other purely computational NAMs", "status": "Scope undecided; no maintainer disposition", "items": [ 9794 ] }, { "method": "Tonsil explant and tumour-on-chip chemo-immunotherapy models from the NAMeRS summit", "status": "Never curated; left on the epic", "items": [ 4873 ] }, { "method": "Usher syndrome NAMs", "status": "Waits on node structure", "items": [ 802, 10822 ] }, { "method": "Murine precision-cut tissue slices across intestine, liver and kidney", "status": "Recorded as a module discussion on organ divergence, not as a model; murine and no NAMO class", "items": [ 9997, 10313 ] }, { "method": "ToxCast/Tox21 assay endpoints as records or evidence (1,570 endpoints; THRB TR-FRET worked example)", "status": "Coverage and a worked example on the project page only; no endpoint name appears in kb/; schema has no disease-agnostic assay record", "items": [ 12858, 13228 ] }, { "method": "ToxCast chemical hit-calls as a structured reference source", "status": "Unmerged; parked on an archived local branch", "items": [ 12682 ] }, { "method": "H295R steroidogenesis assay (OECD TG 456) via biologicalProcessTarget", "status": "Proposal only; gene field names the receptor, not the enzyme", "items": [ 13224 ] }, { "method": "Mitochondrial membrane potential endpoints (APR_HepG2_MitoMembPot, TOX21_MMP) via GO:0051882", "status": "Proposal only; endpoint identity has nowhere to live", "items": [ 13225 ] }, { "method": "EDSP Tier 1 screens and the ToxCast ER and AR pathway models", "status": "Cited on the estrogen project page as history, not as assays in kb/", "items": [ 13219 ] }, { "method": "DNT in vitro battery endpoints (17 processes)", "status": "Lexical coverage report only; no crosswalk recorded in kb/", "items": [ 13424 ] }, { "method": "T-cell dependent antibody response (TDAR) assay", "status": "AOP comparison on a project page; the assay is not recorded in kb/", "items": [ 11857 ] }, { "method": "VAMR assay for trichlorfon, ketamine and nicotine", "status": "Later steps of the issue; open design question of recording one assay once", "items": [ 13450 ] }, { "method": "Lithium-exposed primary human neural progenitors from 83 genotyped donors", "status": "Draft held for the NAM scope decision", "items": [ 13600, 13603, 13602 ] }, { "method": "C. elegans risk-gene mutant panels in a foraging-immobility assay", "status": "Recorded as a knowledge gap, not as models; suicidality genes with no anchor in the entry", "items": [ 13757 ] }, { "method": "GABA-A delta knockout mouse (postpartum depression); Clock, GSK-3beta and Cacna1c mice (bipolar); ESC/E(Z) lymphoblastoid cells (PMDD); stress paradigms and hormone-withdrawal models", "status": "Already cited as evidence but not promoted to model records; stress and withdrawal paradigms blocked on the perturbation slot", "items": [ 13754, 13768 ] }, { "method": "Procedure-based whole-organism models (toxin, diet, stress, surgery) generally", "status": "No perturbation slot on AnimalModel; 50 such models parked in experimental_models as OTHER", "items": [ 13768, 13774 ] } ] }