Post-translational modification (PTM) analysis — phosphorylation, ubiquitination, acetylation, glycosylation, methylation. Uses iPTMnet (sites + enzymes), ProtVar (functional consequences), UniProt (baseline), STRING, ELM (linear motifs), MassIVE/ProteomeXchange (experimental). Use for PTM site annotation, kinase-substrate identification, and PTM-disease associations.

Propose the mechanism by which a missense variant causes loss-of-function (LoF), synthesizing evidence from 5 independent layers: AlphaMissense pathogenicity, AlphaFold structural context, ESMC sequence likelihood, SAE feature disruption, and DynaMut2 stability ΔΔG. Distinguishes 'structural stability LoF' (mis-folding) from 'direct functional disruption' (catalytic / binding / PTM site damage). Use for coding missense variants where you need a mechanistic causal model, not just a pathogenicity score.

Protein-protein interaction (PPI) network analysis — STRING (predicted + experimental), BioGRID (curated), SASBDB (small-angle scattering). Distinguishes physical interactions (binding) from functional associations (co-expression, co-regulation). Use for interactome queries, complex partner identification, and pathway-level interaction analysis.

Post-market safety surveillance and recall/adverse-event RETRIEVAL across the full spectrum of FDA-regulated products that are NOT covered by the drug-AE signal skills: medical devices, food / dietary supplements / cosmetics, veterinary drugs, and drug supply (shortages). Orchestrates openFDA endpoints (MAUDE device adverse events + device recalls + 510(k), CAERS food/supplement/ cosmetic adverse events, veterinary adverse events, drug shortages, and cross-product enforcement/recall reports). USE WHEN the user asks: "are there adverse events for [device / pacemaker / infusion pump / insulin pump]", "device recalls for [firm/product]", "supplement / vitamin / cosmetic adverse reactions", "is [drug] in shortage", "what injectables are on shortage", "veterinary / animal adverse events for [drug] in [dog/cat/horse]", "food recall for listeria", "MAUDE report for [device]", "CAERS reactions for [brand]". DO NOT USE for drug adverse-event SIGNAL detection or disproportionality (PRR / ROR /...

PCR / qPCR primer and oligo design — design forward/reverse primers for a target region (SantaLucia nearest-neighbor thermodynamics), compute melting temperature (Tm) and annealing temperature (Ta), check GC content, and screen an oligo for hairpins and primer-dimers. Use when you need primers for a sequence, want to QC an existing primer pair, or need the Tm of an oligo. Covers the primer-design rules (Tm matching, GC clamp, 3'-end, length) and the tools' constraint quirks.

Cancer treatment recommendations from molecular profile (mutations + cancer type + biomarkers) — FDA-approved + investigational therapies, resistance mechanisms, matching clinical trials, prognosis. Uses CIViC, ClinVar, OpenTargets, ClinicalTrials.gov. Use for tumor-board treatment recommendations, evidence-tiered actionability assessment, and FDA-precedent-driven therapy selection.

Patient stratification for precision medicine — integrate genomic, clinical, and therapeutic data to split patients into responder/non-responder groups, risk tiers, or treatment-decision groups. Use for stratification-by-biomarker, treatment-selection logic, and personalized therapeutic strategy reports per patient subgroup.

Population genetics analysis — allele frequencies (gnomAD, 1000 Genomes), Hardy-Weinberg equilibrium testing, Fst between populations, GWAS associations, evolutionary constraint scores. Use for cross-population variant comparison, ancestry-aware allele frequency lookups, and population-level evolutionary analysis.

Population genetics using the 1000 Genomes Project (IGSR) — superpopulation/population search, sample metadata, variant frequencies across AFR/AMR/EAS/EUR/SAS, ancestry-specific analyses. Use for ancestry comparison, population-aware allele frequency lookups, and 1000-Genomes-cohort-specific analyses (distinct from gnomAD which has different sample composition).

Build and interpret polygenic risk scores (PRS) for complex diseases using GWAS summary statistics. Covers PRS construction (clumping/thresholding, PRS-CS), validation in independent cohorts, ancestry-aware adjustment, and clinical interpretation (population-relative risk, not absolute prediction). Use for PRS-based risk stratification.

Plant genomics and biology research — PlantReactome pathways, Ensembl Plants gene structure, POWO species taxonomy, UniProt annotation, KEGG plant pathways. Handles polyploidy (wheat hexaploidy etc.) and homeologous gene copies. Use for crop-gene annotation, plant secondary metabolism queries, and plant-disease/stress-response biology.

Phylogenetic analysis — de novo multiple sequence alignment (Clustal Omega/MUSCLE/MAFFT via EBI_msa_align) and neighbour-joining/UPGMA tree building (EBI_build_phylogenetic_tree) from your own sequences, plus tree analysis, treeness, saturation (PhyKIT), parsimony-informative sites, alignment gap analysis, DVMC, long-branch detection, BUSCO orthologs. Uses PhyKIT, Biopython, DendroPy. Use to align a set of sequences, build a tree from sequences or an alignment, or for phylogenetic tree QC, multi-gene phylogenomics, evolutionary-rate analysis, and comparative-genomics studies.

Cross-ancestry / cross-biobank phenome-wide association (PheWAS) and replication. Given ONE variant (rsID) or ONE gene, look up every phenotype it associates with across European/UK (UKB-TOPMed), Finnish (FinnGen), Japanese (BioBank Japan), and Taiwanese (TPMI) biobanks, plus exome-wide gene-burden PheWAS (Genebass), then judge whether an association replicates across ancestries or is population-specific. Use whenever the user asks "what else is this variant/gene associated with", "does this association replicate in other ancestries / biobanks", "is this effect East-Asian-specific", "pleiotropy of rsXXX", "phenome scan", or wants to compare effect sizes/allele frequencies of a variant across populations. NOT for the forward direction (trait → which SNPs: use the gwas-* skills), NOT for fine-mapping a locus (use tooluniverse-gwas-finemapping), and NOT for single-SNP mechanism tracing in one population (use tooluniverse-gwas-snp-interpretation).

Drug safety and adverse event analysis — FAERS spontaneous-report mining, FDA black-box warnings, signal detection (PRR, ROR, IC), risk factors by demographic/comorbidity, and label change tracking. Use for post-market safety surveillance, AE signal investigation, drug-AE association strength scoring, and pharmacovigilance reports.

Pharmacokinetic (PK) analysis of concentration-time data — non-compartmental analysis (NCA) for Cmax, Tmax, AUC (0-t and 0-∞), terminal half-life, clearance (CL), volume of distribution (Vd), MRT, and absolute bioavailability (F). Also one-compartment fitting. Use when you have plasma/serum drug concentrations over time after a dose and need PK parameters, or to compute bioavailability from IV + oral AUCs. NOT for ADMET property prediction from structure (use tooluniverse-admet-prediction).

Pharmacogenomics (PGx) research — drug-gene interactions (CPIC, PharmGKB), CPIC dosing guidelines, variant-drug-response associations, ethnic-allele-frequency considerations, and metabolizer-status scoring. Use for PGx-informed dosing recommendations, CYP/HLA pharmacogenomic allele interpretation, and clinically-actionable PGx report generation.

Find the real protein target(s) of a peptide from its sequence — peptide target deorphanization / off-target identification, for ANY target class (GPCR, ion channel, protease, cytokine/growth-factor receptor, enzyme, integrin), not only GPCRs. Use when a peptide has a phenotype but does not bind its hypothesized target, when a peptide binds a target in one species or assay but not another, or to screen candidate targets for an orphan peptide. A target-class router steers a multi-route keyless pipeline (PROSITE/ELM motif, BLAST homology, HGNC/InterPro/GPCRdb/GtoPdb target-family enumeration, OpenTargets phenotype anchor, EnsemblCompara/Alliance cross-species reconciliation) plus optional NVIDIA-NIM co-folding (Boltz2, AlphaFold2-Multimer, OpenFold3) for structural confirmation.

Connect GWAS variants to biological pathways and druggable targets. Maps GWAS hits to causal genes (via fine-mapping/eQTL), then to pathways (Reactome, KEGG, WikiPathways), then to existing drugs hitting those pathways. Use for pathway-level disease mechanisms, druggable-pathway prioritization from GWAS, SNP-to-pathway-to-target tracing, and tissue-specific eQTL evidence for drug target hypotheses.

Organic chemistry reasoning guide for reaction product prediction, mechanism analysis (electrophilic/nucleophilic substitution, addition, elimination, pericyclic, radical), and spectroscopy interpretation (1H/13C NMR, IR, MS). Reasons from first principles (electron flow, kinetic vs thermodynamic) rather than pattern-matching named reactions. Use for organic synthesis problems and mechanism explanations.

Non-coding RNA analysis — miRNAs (miRBase, miRDB targets), lncRNAs (LNCipedia, RNAcentral), circRNAs, snoRNAs, and other ncRNA classes. Distinct mechanisms per class — miRNAs repress mRNA; lncRNAs scaffold/decoy/enhance. Use for ncRNA function prediction, miRNA-target prediction, lncRNA functional annotation, and ncRNA-disease association queries.