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.

Assess drug-drug interactions — CYP metabolic interactions (substrate/inhibitor/inducer), transporter (P-gp, BCRP, OATP) effects, pharmacodynamic synergy/antagonism, clinical significance scoring, and management recommendations. Use for polypharmacy review, prescribing decision support, and safety analysis when adding or switching drugs.

Dose-response / concentration-response curve fitting — IC50, EC50, Hill slope, Emax/Emin efficacy, and relative potency from paired concentration vs response data (enzyme/cell assays, drug screening, agonist/antagonist pharmacology). Fits the 4-parameter logistic (Hill sigmoidal) model. Use when you have concentrations + responses and need a potency value, to compare two compounds' potency, or to judge curve quality. NOT for image-derived dose-response (use tooluniverse-image-analysis) and NOT for survival/regression (use tooluniverse-statistical-modeling).

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.

Add custom local tools to ToolUniverse alongside the 1000+ built-in tools. Covers JSON-config tools (simplest, no code), Python class tools (REST/SOAP/GraphQL APIs, computational logic), and best-practices for return schemas. Use for wrapping new APIs, adding domain-specific computations, or contributing tools to the registry.

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.

Solve quantitative problems in biophysics — pharmacokinetics (PK volume of distribution, clearance, half-life), epidemiology (R0, attack rate), toxicology (LD50, NOAEL), population genetics (Hardy-Weinberg, Fst), enzyme kinetics (Michaelis-Menten), thermodynamics. Use for first-principles quantitative biology calculations, dose calculations, exposure assessment, and biophysical-property estimation.

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.

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.

Strategic clinical trial design feasibility assessment. Analyzes 6 dimensions (endpoint, population, comparator, effect size, duration, regulatory pathway) using precedent trials and FDA guidance. Produces enrollment projections, endpoint recommendations, and approval-pathway analysis. Use for trial-protocol design, power/sample-size estimation, comparator selection, and FDA submission strategy. Driven by precedent-based reasoning rather than first-principles math.

Compute and interpret validated bedside clinical risk scores and pretest probabilities for an INDIVIDUAL patient — pick the right score for the scenario, gather inputs, run the deterministic calculator tool, and read the result against an interpretation table. Covers CHA2DS2-VASc (AF stroke risk), HAS-BLED (bleeding on anticoagulation), CURB-65 (pneumonia severity / admit decision), qSOFA (sepsis screen), Child-Pugh + MELD-Na (cirrhosis severity / transplant priority), Wells DVT and Wells PE (VTE pretest probability), ASCVD (10-year cardiovascular risk / statin decision), and eGFR CKD-EPI (kidney function / drug dosing). Use when asked things like "stroke risk for this AF patient", "should this patient be anticoagulated", "pneumonia severity — admit or not?", "sepsis screen this patient", "DVT/PE pretest probability", "10-year cardiovascular risk", "cirrhosis severity / MELD score", or "eGFR / kidney function". Pairs CHA2DS2-VASc with HAS-BLED to weigh anticoagulation. NOT for polygenic/genetic risk (use tooluniverse-polygenic-risk-score), NOT for population-level epidemiology/incidence (use tooluniverse-epidemiological-analysis), and NOT for diagnostic test sensitivity/specificity/likelihood-ratio math (use tooluniverse-diagnostic-test-evaluation).

Search and retrieve clinical practice guidelines from 12+ authoritative sources — NICE, WHO, NCCN, AHA, ADA, SIGN, USPSTF, IDSA, NIH consensus, ESMO/ESC/EASL European societies, and US specialty associations. Use for evidence-graded treatment recommendations, dosing protocols, screening guidance, and authoritative-source-prioritized clinical guidance (NICE/WHO ranked above society guidelines).