tooluniverse-protein-therapeutic-design

Router skill for ToolUniverse tasks. First checks if specialized tooluniverse skills (105+ skills covering disease/drug/target research, gene-disease associations, clinical decision support, genomics, epigenomics, proteomics, comparative genomics, chemical safety, toxicology, systems biology, and more) can solve the problem, then falls back to general strategies for using 2300+ scientific tools. Covers tool discovery, multi-hop queries, comprehensive research workflows, disambiguation, evidence grading, and report generation. Use when users need to research any scientific topic, find biological data, or explore drug/target/disease relationships. ALSO USE for any biology, medicine, chemistry, pharmacology, or life science question — even simple factoid questions like "how many X in protein Y", "what drug interacts with Z", "what gene causes disease W", or "translate this sequence". These questions benefit from database lookups (UniProt, PubMed, ChEMBL, ClinVar, GWAS Catalog, etc.) rather than answering from memory alone. When in doubt about a scientific fact, USE THIS SKILL to verify against real databases.

End-to-end variant-to-mechanism analysis: given a genetic variant (rsID or coordinates), trace its functional impact from regulatory context (GWAS, eQTL, RegulomeDB, ENCODE) through target gene identification (GTEx, OpenTargets L2G) to downstream pathway and disease biology (STRING, Reactome, GO enrichment, disease associations). Produces an evidence-graded mechanistic narrative linking genotype to phenotype. Use when asked "how does this variant cause disease?", "what is the mechanism of rs7903146?", "trace variant to pathway", or "connect this GWAS hit to biology".

Systematic clinical variant interpretation from raw variant calls to ACMG-classified recommendations with structural impact analysis. Aggregates evidence from ClinVar, gnomAD, CIViC, UniProt, and PDB across ACMG criteria. Produces pathogenicity scores (0-100), clinical recommendations, and treatment implications. Use when interpreting genetic variants, classifying variants of uncertain significance (VUS), performing ACMG variant classification, or translating variant calls to clinical actionability.

Comprehensive functional annotation of protein variants — pathogenicity, population frequency, structural context, and clinical significance. Integrates ProtVar (map_variant, get_function, get_population) for protein-level mapping and structural context, ClinVar for clinical classifications, gnomAD for population frequency with ancestry data, CADD for deleteriousness scores, and ClinGen for gene-disease validity. Produces a structured variant annotation report with evidence grading. Use when asked about protein variant impact, missense variant pathogenicity, ProtVar annotation, variant functional context, or combining population and structural evidence for a variant.

Production-ready VCF processing, variant annotation, mutation analysis, and structural variant (SV/CNV) interpretation for bioinformatics questions. Parses VCF files (streaming, large files), classifies mutation types (missense, nonsense, synonymous, frameshift, splice, intronic, intergenic) and structural variants (deletions, duplications, inversions, translocations), applies VAF/depth/quality/consequence filters, annotates with ClinVar/dbSNP/gnomAD/CADD via ToolUniverse, interprets SV/CNV clinical significance using ClinGen dosage sensitivity scores, computes variant statistics, and generates reports. Solves questions like "What fraction of variants with VAF < 0.3 are missense?", "How many non-reference variants remain after filtering intronic/intergenic?", "What is the pathogenicity of this deletion affecting BRCA1?", or "Which dosage-sensitive genes overlap this CNV?". Use when processing VCF files, annotating variants, filtering by VAF/depth/consequence, classifying mutations, interpreting structural variants, assessing CNV pathogenicity, comparing cohorts, or answering variant analysis questions.

Design and evaluate vaccine candidates using computational immunology tools. Covers epitope prediction (MHC-I/II binding via IEDB), population coverage analysis, antigen selection, adjuvant matching, and immunogenicity assessment. Integrates IEDB for epitope prediction, UniProt for antigen sequences, PDB/AlphaFold for structural epitopes, BVBRC for pathogen proteomes, and literature for clinical precedent. Use when asked about vaccine design, epitope prediction, immunogenicity, MHC binding, T-cell epitopes, B-cell epitopes, or population coverage for vaccine candidates.

Assess chemical and drug toxicity via adverse outcome pathways, real-world adverse event signals, and toxicogenomic evidence. Integrates AOPWiki (AOPWiki_list_aops, AOPWiki_get_aop) for mechanism- level pathway tracing, FAERS for post-market adverse event quantification, OpenFDA for label mining, and CTD for chemical-gene-disease evidence. Produces structured toxicity reports with evidence grading (T1-T4). Use when asked about toxicity mechanisms, adverse outcome pathways, AOP mapping, FAERS signal detection, or chemical-disease relationships for drugs or environmental chemicals.

Gather comprehensive biological target intelligence from 9 parallel research paths covering protein info, structure, interactions, pathways, expression, variants, drug interactions, and literature. Features collision-aware searches, evidence grading (T1-T4), explicit Open Targets coverage, and mandatory completeness auditing. Use when users ask about drug targets, proteins, genes, or need target validation, druggability assessment, or comprehensive target profiling.

Comprehensive systems biology and pathway analysis using multiple pathway databases (Reactome, KEGG, WikiPathways, Pathway Commons, BioModels). Performs pathway enrichment, protein-pathway mapping, keyword searches, and systems-level analysis. Use when analyzing gene sets, exploring biological pathways, or investigating systems-level biology.

Comprehensive structural variant (SV) analysis skill for clinical genomics. Classifies SVs (deletions, duplications, inversions, translocations), assesses pathogenicity using ACMG-adapted criteria, evaluates gene disruption and dosage sensitivity, and provides clinical interpretation with evidence grading. Use when analyzing CNVs, large deletions/duplications, chromosomal rearrangements, or any structural variants requiring clinical interpretation.

Integrate structural biology data with proteomics for drug target validation. Retrieves protein structures from PDB (RCSB, PDBe), AlphaFold predictions, antibody structures (SAbDab), GPCR data (GPCRdb), binding pocket analysis (ProteinsPlus), and ligand interactions (BindingDB). Use when asked to find structures for a drug target, identify binding site ligands, cross-validate drug binding with structural data, assess structural druggability, or compare experimental vs predicted structures.

Research stem cells, iPSCs, organoids, and cell differentiation using ToolUniverse tools. Covers pluripotency marker identification, differentiation pathway analysis, organoid model characterization, cell type annotation, and disease modeling. Integrates CellxGene/HCA for single-cell atlas data, CellMarker for cell type markers, GEO for stem cell datasets, and pathway tools for differentiation signaling. Use when asked about stem cells, iPSCs, organoids, cell reprogramming, pluripotency, differentiation protocols, or 3D culture models.