Gene-disease association analysis across DisGeNET, OpenTargets, Monarch, OMIM, GenCC, Orphanet. Cross-references multiple sources for evidence-graded association reports with concordance scoring (5/5 sources agree → strong, 1/5 → weak). Use for 'which diseases is gene X associated with' or 'which genes cause disease Y' queries with quantitative confidence.

Histone-modification ChIP-seq, ATAC-seq accessibility, chromatin state, and TF binding analysis from ENCODE, Roadmap Epigenomics, ChIP-Atlas. Use for chromatin-state-by-tissue queries, TF-binding-by-region, regulatory landscape mapping, and ENCODE-cCRE annotations. For DNA methylation use tooluniverse-epigenomics; for RNA-seq use tooluniverse-rnaseq-deseq2.

End-to-end observational epidemiology analysis — from research question (PECO Population/Exposure/Comparator/Outcome) to publication-ready statistical report. Covers cohort/case-control/cross-sectional design, regression with confounders, propensity scoring, sensitivity analysis. Writes Python code for every step. Use for epidemiology study analysis, NHANES/UK-Biobank-style analyses.

Enzyme kinetics — Michaelis-Menten Km, Vmax, kcat (turnover), and kcat/Km (catalytic efficiency / specificity constant) from substrate-velocity data, plus inhibition-mechanism analysis (competitive / uncompetitive / non-competitive, Ki). Fits the MM equation by nonlinear regression (and reports Lineweaver-Burk for reference). Use when you have substrate concentrations and initial reaction velocities and need kinetic parameters or to classify an inhibitor. NOT for BRENDA database lookups of published constants (use the BRENDA tools).

Search and analyze electron microscopy data — cryo-EM density maps (EMDB), fitted atomic models (PDB), raw micrograph datasets (EMPIAR), and cryo-electron tomography volumes (CryoET Data Portal). Use for finding 3D structural data on a protein/complex, comparing experimental EM resolution to AlphaFold confidence, and accessing raw EM data for re-processing.

Ecology, biodiversity, and conservation biology research — species identification (GBIF, NCBI Taxonomy), invasive species impact, ecosystem dynamics, conservation status (IUCN), niche ecology. Use for biodiversity questions, species comparison, invasion biology, conservation prioritization, and ecology-related literature search.

Drug-combination synergy analysis — quantify whether two drugs together are synergistic, additive, or antagonistic using the standard reference models (Bliss independence, HSA / highest single agent, Loewe additivity, ZIP, and the Chou-Talalay Combination Index). Use when you have measured single-drug and combination effects (inhibition/viability) and need a synergy score. Explains which model to use, what data each one needs, and how to read the score. NOT for looking up pre-computed synergy in a database (use the SYNERGxDB tool / cell-line-profiling skill).

Comprehensive drug profiling — mechanism, primary/secondary targets, drug interactions, clinical-trial status, adverse events (FAERS), pharmacogenomics, and approval history. Use for full drug investigation reports, 'tell me about drug X' queries, and assembling drug profiles for clinicians, researchers, or regulatory work.

Identify drug repurposing candidates via target-based, compound-based, and disease-based strategies. Combines drug-target-disease network reasoning with mechanism rationale, clinical-trial precedent, and patent/regulatory feasibility. Use for hypothesis-generating repurposing for orphan diseases, finding existing drugs for new indications, and prioritizing candidates by evidence and feasibility.

Drug regulatory and approval research — FDA substance registry, ATC/EPC classification, EMA decisions, generic-drug status, FDA Orange Book exclusivity, NDA/BLA pathways. Use for jurisdiction-aware approval status (FDA vs EMA), generic vs brand availability, exclusivity expiry tracking, and regulatory pathway selection. Always specifies the market when reporting status.

Trace drug mechanism of action — primary target → downstream signaling → pathway perturbation → tissue/organ effect → clinical outcome. Uses DrugBank, ChEMBL, KEGG, Reactome, STRING. Use for understanding how a drug works, identifying off-target effects, mechanism-based combination therapy design, and writing mechanism sections of reports.

Generate comprehensive disease research reports covering genetics (causal genes, GWAS, OMIM), pathways (Reactome, KEGG), drugs (existing therapies, repurposing candidates), clinical trials, epidemiology (prevalence, incidence), and phenotypes (HPO). Use for full disease overviews, comprehensive disease characterization, and orphan/rare-disease profiling.

Diagnostic test / biomarker accuracy — sensitivity, specificity, PPV, NPV, likelihood ratios, accuracy from a 2x2 table; ROC curve, AUC, and the optimal cutoff (Youden) for a continuous biomarker; and post-test probability via Bayes. Use when you have test results vs a gold standard (binary 2x2, or a continuous score + true labels) and need to judge how good the test is, pick a threshold, or compute the probability of disease given a result. Emphasizes the prevalence-dependence of PPV/NPV.

Find and evaluate research datasets for any scientific question. Maps research questions to required study designs (longitudinal vs cross-sectional, observational vs experimental, single-cohort vs multi-cohort). Use when the user asks 'find data about X', 'where can I get data on Y', or needs a specific cohort/survey/repository. Covers GEO, ArrayExpress, dbGaP, NHANES, UK Biobank, ClinicalTrials.gov, GWAS Catalog, and 30+ scientific repositories.

Universal data access patterns for downloading and parsing scientific data when ToolUniverse tools don't cover the source, only return metadata, or you need bulk records. Use for VCF/h5ad/BAM/SDF/GCT parsing, multi-step API workflows (search to filter to download to parse), thousands of records at once, or sources with no dedicated tool. Write Python code via Bash for every step.

Integrate computed statistical results (DEGs, GWAS hits, associations) with biological context from ToolUniverse databases (UniProt, GO, Reactome, ClinVar, OpenTargets). Use for adding gene function/pathway/disease annotations to a result list, building biological narrative around statistical findings, and going beyond p-values to mechanism.

Analyze CRISPR-Cas9 genetic screens — MAGeCK gene-level scores, sgRNA count QC, replicate correlation, hit prioritization, and pathway GSEA on screen output. Use for genome-wide essentiality screens, synthetic-lethality discovery, dropout vs positive-selection screen analysis, target identification, and resistance-screen interpretation. Includes screen-QC and statistical thresholds.

Cross-species gene comparison and ortholog analysis. Integrates Ensembl Compara orthologs, NCBI Gene, UniProt, OLS, Monarch, and OpenTargets to identify orthologs, paralogs, sequence conservation, functional conservation across species, and lineage-specific gene gains/losses. Use for phylogenetic gene tracing, model-organism mapping, and evolutionary-genomics queries.

Install, set up, verify, update, pin, uninstall, or troubleshoot the ToolUniverse plugin on OpenAI Codex. ALWAYS consult this skill for any of those — don't answer from memory, because the exact marketplace name (mims-harvard/ToolUniverse), the "codex plugin marketplace add" then "codex plugin add -m tooluniverse" flow, Codex's startup auto-upgrade behavior, the uvx tooluniverse MCP server, and the API-key env vars are easy to get wrong. Use it whenever someone wants to get ToolUniverse (or "the 1000+ scientific tools" / "the harvard tools") working on Codex, says the Codex plugin or its tools/skills won't load, hits a uvx or MCP-server startup error, asks how Codex updates it, wants to pin or remove it, or finds it running an old tool version — even if they never say the word "plugin". Not for the Claude Code plugin (use tooluniverse-claude-code-plugin), for running research with the tools, or for authoring new tools or skills.

AI-driven patient-to-trial matching for precision oncology and rare-disease care. Transforms a patient's molecular profile (mutations, biomarkers, expression) and clinical state into ranked clinical-trial recommendations with evidence tiers. Searches ClinicalTrials.gov, the EU CTIS register (European/EEA trials), AND the ISRCTN registry (UK/international) plus cross-references CIViC, OpenTargets, ChEMBL, and FDA labels. Use for matching patients to trials by genotype, biomarker-driven trial selection, trial-eligibility scoring, and finding trials across the US, Europe, and the UK.