Extends the antimicrobial drug–bug mechanism layer to antifungal therapy: ergosterol-synthesis (azoles/allylamines), membrane-ergosterol-binding (polyenes), cell-wall glucan-synthesis (echinocandins), and antimetabolite (flucytosine) target modules, plus an intrinsic-resistance gating axis. All five modules are now built and validated.
5 diseases
5 modules
Six antimicrobial mechanism modules now cover the major antibacterial target classes plus the lifestyle-gating axis:
8 diseases
8 modules
Extends the antimicrobial drug–bug mechanism layer to antiviral therapy: viral-target modules (polymerase, protease, entry/fusion, integrase, release) plus the latency/reservoir gating axis. Five target-class modules plus the gating module are now built and validated.
6 diseases
7 modules
Assess to what extent dismech's environmental-exposure and evidence model aligns with the Adverse Outcome Pathway framework & the expanded AOP Evidence Model (EMOD), with an eye towards identifying ways dismech might be expanded and enriched by incorporating AOPs, ways dismech might seed development of new AOPs, and ways that AOP EMOD might adopt evidence modeling approaches from dismech.
FRAMEWORK_ALIGNMENTEVIDENCEEXTERNAL_COLLABORATIONENVIRONMENTAL_EXPOSURESCHEMA_EVOLUTION
3 diseases
10 modules
Comprehensive curation of autoimmune diseases for the dismech knowledge base, covering diverse autoimmune mechanisms including organ-specific, systemic, and autoinflammatory conditions.
34 diseases
DisMech plus OpenScientist can become an auditable experiment-suggestion layer for disease biology: DisMech stores a computable pathograph, OpenScientist searches and ranks mechanistic gaps, and a protocol layer turns selected gaps into standardized experiments that can be reviewed by humans and...
1 disease
Curation of cancers with precise genetic etiology and well-characterized pathophysiological progression, prioritizing single-gene/fusion drivers, pathway clarity, and therapeutic relevance.
DISEASE_DOMAINONCOLOGYFLAGSHIP
5 diseases
12 modules
1 drug
1 phenotype
The treatment and pathophysiology sections describe the same biological process from opposite directions but are not structurally linked:
1 disease
2 modules
Explore how dismech can contribute to the childhood / pediatric / AYA cancer data ecosystem, with a focus on structured disease mechanism curation for pediatric malignancies and direct alignment with the NCI Childhood Cancer Data Initiative (CCDI).
This project aims to curate comprehensive pathophysiology entries for major chronic diseases in the Disorder Mechanisms Knowledge Base. Chronic diseases represent long-term conditions that require ongoing management and significantly impact quality of life.
39 diseases
Systematically collect recent clinical Practice Guideline citations from PubMed for dismech disorders, generalizing the Fanconi anemia care-guideline mining (issue #4878). Batch 1 captures the top 40 disorders by recent-guideline availability; batch 2 is a 10-disorder rare-disease slice that mirrors the Fanconi anemia case — together a snippet-verification and gap-assessment worklist.
CLINICAL_GUIDELINESEVIDENCEPUBMEDPHENOTYPE_COVERAGECURATION_WORKFLOWRARE_DISEASE
47 diseases
Goal: curate comorbidity/trajectory evidence from the literature (complementary to EHR-derived signals such as Disease Trajectories / Distraj), with directionality when supported. Do not start curation yet; this is a scoping log and candidate list.
Comprehensive curation of Epidermolysis Bullosa (EB) for the dismech knowledge base. EB is a group of inherited mechanobullous disorders characterized by skin and mucosal fragility due to mutations in structural proteins of the dermal-epidermal junction. The four major types are defined by the ul...
6 diseases
This project records a practical curation plan for representing epilepsy in dismech at a level where mechanisms are coherent and clinically useful.
4 diseases
Close the FA phenotype-annotation gap identified by the Connelly et al. custom HPO profile (PMID:41728284); 203 profile terms were absent from the dismech entry. Batch 1 added 17; ~186 remain.
PHENOTYPE_COVERAGEHPORARE_DISEASEDNA_REPAIR
1 disease
1 module
3 phenotypes
This project tracks how Gene2Phenotype (G2P) disease rows map onto dismech's disease-centric knowledge model, with the goal of turning comparison output into curation triage rather than a one-off research exercise.
How dismech references external gene sets (MSigDB/KEGG/WikiPathways/Hallmark/ cell-type signatures) and their curated GO interpretations, and aligns a gene set's curated biological processes against a disease pathograph.
INFRASTRUCTUREGENE_SETSGOALIGNMENT
30 diseases
Curating the nine FDA-approved candidate gerotherapeutics prioritized by Kulkarni et al. 2022 into the hallmark-of-aging mechanism modules, so that "drug X targets hallmark Y" is a queryable treatment link rather than a claim in a review table.
11 modules
This project organizes curation of Mendelian neurodevelopmental disorders caused by ionotropic glutamate receptor subunit genes, starting with:
3 diseases
One-off campaign to visit every disorder entry whose references or inlined evidence lack a title, backfill the missing title, AND manually re-read each cited source to confirm the findings are truly supported. One PR per disease, each driven and monitored to green-and-mergeable by an isolated subagent in an isolated temporary worktree.
qualityevidencereferencescampaign
Use DisMech as a validation/interpretation layer for computational pipelines that discover causal gene-to-trait relationships via GWAS, Perturb-seq, and causal modeling. The pilot application is the Ota et al. (Nature 2025) framework that builds three-layer causal graphs:
23 diseases
Represent computable EHR/OMOP case-finding queries that are predicated on a disease mechanism (not just consensus criteria), so a mechanism-derived scan for latent/mild carriers is never conflated with a validated phenotype — with paired population (EHR biobank) and mechanistic (NAM) tests.
METHODOLOGYEHRPHENOTYPE_ALGORITHMNAMCHANNELOPATHY
4 diseases
2 phenotypes
This project tracks curation of high-priority inborn errors of metabolism (IEMs), with emphasis on neonatal and early-childhood presentations that are common in newborn screening workflows and NICU practice.
35 diseases
Mondo is actively debating how to represent the inherited vs. de novo distinction in the ontology (see #8074 on tuberous sclerosis, #8483 on genetic epilepsies). The dismech schema already has slots for denovorate, penetrance, expressivity, and parentoforigineffect on Inheritance objects, but the...
This project organizes curation of lysosomal storage diseases (LSDs) in dismech, with a specific focus on where to lump, where to split, and where to use a project umbrella rather than forcing everything into one root disease file.
13 diseases
Date: 2026-02-11
Create a mechanism-centered dismech entry for obesity caused by disruption of the leptin-melanocortin-4 receptor pathway. The scope includes:
1 disease
This project curates the three known disorders of the mitochondrial protein lipoylation pathway. Lipoylation is a post-translational modification essential for the function of four mitochondrial enzyme complexes: pyruvate dehydrogenase (PDH), alpha-ketoglutarate dehydrogenase (OGDH), branched-cha...
3 diseases
Replace brittle, hand-maintained SQL IN (...) code lists with a reproducible MONDO-driven mapping pipeline that generates versioned SNOMED/ICD concept sets for OMOP queries.
Bridge dismech's disease-centric curation model to Monarch NAMO without importing the full NAMO schema into dismech.
MODELSNAMRARE_DISEASECROSSWALK
5 diseases
Use the NCI Thesaurus NCIT:P302 (Accepted_Therapeutic_Use_For) annotation as structured, citable evidence for dismech treatment sections, and as a completeness signal for which accepted drug therapies are missing from disorder entries (and which indications map to diseases not yet curated).
treatmentsstructured-sourcescompletenessncit
Curate the WHO-recognized neglected tropical diseases (NTDs) in the Disorder Mechanisms Knowledge Base, with emphasis on pathogen life cycles, transmission routes, immune evasion, and chronic morbidity mechanisms. The current WHO list includes 21 diseases or disease groups, which maps to 22 KB fi...
26 diseases
Conditions where the immune system attacks the nervous system (CNS or PNS), causing inflammation, demyelination, or neuronal damage.
DISEASE_DOMAINNEUROLOGYIMMUNOLOGY
7 diseases
This project focuses on disorders commonly managed in neonatal intensive care units (NICUs), spanning prematurity complications, neonatal critical care, and high-impact genetic diseases that present in the newborn period.
22 diseases
Integrate the dismech knowledge base with the cross-organ fibrosis atlas from the Saez-Rodriguez lab (Heidelberg / EMBL-EBI), an open single-cell resource mapping shared and organ-specific fibrotic gene programs across heart, liver, kidney, and lung.
Three-pass LLM classification survey across 91 pathophysiology nodes from 8 disorders to test whether a small `biological_scale:` enum (MOLECULAR / CELLULAR / TISSUE / ORGANISM) is viable as an incremental addition to the pathograph schema. Finding: 4-value scale-only enum works; no STATE additions needed; ~41% of sampled nodes are bundle candidates that the slot would surface. (Working name during the analysis was `kind:`; renamed on completion once the enum's scale-only nature was confirmed — see historical note in the report body.)
SCHEMA_EVOLUTIONPATHOPHYSIOLOGYFEASIBILITY_ANALYSIS
8 diseases
Catalog rare MONDO diseases that lack ICD mappings, with priority on missing ICD-11 Foundation (icd11f / icd11.foundation) mappings.
Catalogue of diseases in the Reactome pathway database, cross-referenced with dismech entries. Reactome curates disease-associated pathway variants, providing mechanistic context for how mutations perturb normal biological processes.
77 diseases
Anatomy/syndrome-oriented curation of infections of the respiratory tract (upper and lower), complementing the drug-mechanism-oriented ANTIMICROBIAL, ANTIVIRAL, and ANTIFUNGAL projects. Seeds the existing respiratory-infection entries and tracks the major coverage gaps (bacterial pneumonia, atypical pneumonias, pertussis, fungal pneumonias, croup, sinusitis/pharyngitis).
DISEASE_DOMAININFECTIOUS_DISEASERESPIRATORY
27 diseases
2 modules
Curate retinopathy and retinal dystrophy branches for the dismech knowledge base with explicit granularity rules. The goal is to avoid duplicated pathographs while still separating entities whose proximal pathobiology, diagnosis, or management genuinely diverge.
5 diseases
Comprehensive curation of skeletal dysplasias for the dismech knowledge base, prioritizing genetic skeletal disorders with defined molecular pathogenesis and clear genotype-phenotype correlations. This project focuses on disorders where: 1. Single-gene or well-defined genetic drivers are establis...
6 diseases
Spaceflight biology provides unique insights into disease mechanisms through microgravity environments, radiation exposure, and physiological deconditioning. Many dismech disorders have direct relevance to space health research, and NASA's Open Science Data Repository (OSDR) contains datasets tha...
Diseases where protein structure determination (PDB X-ray crystallography, cryo-EM) or computational structure prediction (AlphaFold) has been key to understanding pathophysiology, enabling drug design, or interpreting variant pathogenicity.
Reading the three AOP-Wiki pathways that terminate at impaired T-cell dependent antibody response against dismech's own humoral-immunity modeling, in both directions: what the comparison exposes about dismech, and what dismech exposes as knowledge gaps in the TDAR AOPs.
FRAMEWORK_ALIGNMENTEVIDENCEEXTERNAL_COLLABORATIONIMMUNOLOGYKNOWLEDGE_GAP
9 diseases
8 modules
Explore how dismech's structured mechanism models can serve as a knowledge substrate for computational tumor microenvironment (TME) modeling, especially multiscale agent-based simulators, reinforcement-learning-guided therapy optimization, and cancer digital twin frameworks.
15 diseases
2 modules
Align the dismech knowledge base with the CZI Virtual Cell initiative, enabling disease mechanism data to connect with single-cell foundation models (scGPT, UCE, TranscriptFormer, GREmLN, rBio) and the CELLxGENE Census data platform.