All Skills

Provide differential diagnosis for patients with suspected rare diseases based on phenotype and genetic data. Matches symptoms to HPO terms, identifies candidate diseases from Orphanet/OMIM, prioritizes genes for testing, interprets variants of uncertain significance. Use when clinician asks about rare disease diagnosis, unexplained phenotypes, or genetic testing interpretation.

Retrieves protein structure data from RCSB PDB, PDBe, and AlphaFold with protein disambiguation, quality assessment, and comprehensive structural profiles. Creates detailed structure reports with experimental metadata, ligand information, and download links. Use when users need protein structures, 3D models, crystallography data, or mention PDB IDs (4-character codes like 1ABC) or UniProt accessions.

Build AI scientist systems using ToolUniverse Python SDK for scientific research. Use when users need to access 1000++ scientific tools through Python code, create scientific workflows, perform drug discovery, protein analysis, genomics analysis, literature research, or any computational biology task. Triggers include requests to use scientific tools programmatically, build research pipelines, analyze biological data, search literature, predict drug properties, or create AI-powered scientific workflows.

Analyze drug safety signals from FDA adverse event reports, label warnings, and pharmacogenomic data. Calculates disproportionality measures (PRR, ROR), identifies serious adverse events, assesses pharmacogenomic risk variants. Use when asked about drug safety, adverse events, post-market surveillance, or risk-benefit assessment.

Fix failing ToolUniverse tools by diagnosing test failures, identifying root causes, implementing fixes, and validating solutions. Use when ToolUniverse tools fail tests, return errors, have schema validation issues, or when asked to debug or fix tools in the ToolUniverse framework.

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.

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.

Skill: Gene Regulatory Network Analysis

Analyze HLA genes, MHC binding, epitope-MHC associations, and immunogenomics for transplant compatibility, vaccine design, and immunotherapy. Integrates IMGT, IEDB, BVBRC, UniProt, and DGIdb. Use for HLA typing interpretation, antigen presentation analysis, MHC restriction, neoantigen prediction context, and transplant immunology.

Design novel protein therapeutics (binders, enzymes, scaffolds) using AI-guided de novo design. Uses RFdiffusion for backbone generation, ProteinMPNN for sequence design, ESMFold/AlphaFold2 for validation. Use when asked to design protein binders, therapeutic proteins, or engineer protein function.

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.

Comprehensive patient stratification for precision medicine by integrating genomic, clinical, and therapeutic data. Given a disease/condition, genomic data (germline variants, somatic mutations, expression), and optional clinical parameters, performs multi-phase analysis covering disease disambiguation, genetic risk assessment, disease-specific molecular stratification, pharmacogenomic profiling, comorbidity/DDI risk, pathway analysis, clinical evidence and guideline mapping, clinical trial matching, and integrated outcome prediction. Generates a quantitative Precision Medicine Risk Score (0-100) with risk tier assignment, treatment algorithm, pharmacogenomic guidance, clinical trial matches, and monitoring plan.

Analyze spatial transcriptomics data to map gene expression in tissue architecture. Supports 10x Visium, MERFISH, seqFISH, Slide-seq, and imaging-based platforms. Performs spatial clustering, domain identification, cell-cell proximity analysis, spatial gene expression patterns, tissue architecture mapping, and integration with single-cell data. Use when analyzing spatial transcriptomics datasets, studying tissue organization, identifying spatial expression patterns, mapping cell-cell interactions in tissue context, characterizing tumor microenvironment spatial structure, or integrating spatial and single-cell RNA-seq data for comprehensive tissue analysis.

Add custom local tools to ToolUniverse and use them alongside the 1000+ built-in tools. Use this skill when a user wants to: create their own tool for a private or custom API, add a local tool to their workspace, integrate an internal service with ToolUniverse, or use a custom tool via the MCP server or Python API. Covers both the JSON config approach (easiest, no Python needed) and the Python class approach (full control). Also covers how to verify tools loaded correctly and how to call them. Also covers the plugin package approach for reusable, shareable, pip-installable tool sets.

Research plant genes, pathways, and species using PlantReactome, Ensembl Plants, POWO, UniProt, KEGG, and literature tools. Covers plant pathway analysis, gene function annotation, species identification, crop genomics, and comparative plant biology. Use when asked about plant genes, Arabidopsis, crop improvement, plant pathways, plant metabolism, photosynthesis, plant development, or plant species identification.

Computational analysis framework for spatial multi-omics data integration. Given spatially variable genes (SVGs), spatial domain annotations, tissue type, and disease context from spatial transcriptomics/proteomics experiments (10x Visium, MERFISH, DBiTplus, SLIDE-seq, etc.), performs comprehensive biological interpretation including pathway enrichment, cell-cell interaction inference, druggable target identification, immune microenvironment characterization, and multi-modal integration. Produces a detailed markdown report with Spatial Omics Integration Score (0-100), domain-by-domain characterization, and validation recommendations. Uses 70+ ToolUniverse tools across 9 analysis phases. Use when users ask about spatial transcriptomics analysis, spatial omics interpretation, tissue heterogeneity, spatial gene expression patterns, tumor microenvironment mapping, tissue zonation, or cell-cell communication from spatial data.

Population genetics research using the 1000 Genomes Project (IGSR) -- search populations by superpopulation ancestry (AFR, AMR, EAS, EUR, SAS), retrieve samples by population code, list available data collections, and integrate with GWAS tools for population stratification analysis. Use when users ask about 1000 Genomes populations, sample ancestry, allele frequency variation across continental groups, population-specific GWAS interpretation, or IGSR data collections like the 30x high-coverage resequencing or HGSVC.

Drug mechanism of action investigation -- systematic strategy to trace a drug from its primary target through pathways to clinical outcomes, identify off-target effects, and combine regulatory labels with literature evidence for a complete mechanism picture.

Neuroscience research and reasoning workflows using ToolUniverse tools. Covers computational neuroscience (rate models, integrate-and-fire neurons, synaptic plasticity, network dynamics), neuroanatomy (cortical regions, basal ganglia, cerebellum, brainstem, model organism connectomes), neurophysiology (ion channels, action potentials, synaptic transmission), neural circuits (E/I balance, oscillations, central pattern generators), synaptic dynamics (STDP, short-term plasticity, neuromodulation), neurodegenerative diseases (Alzheimer's, Parkinson's, ALS, Huntington's), and clinical neurology (cranial nerves, stroke localization, neuromuscular disorders). Use when researchers ask about brain regions, neural computation, firing rates, synaptic plasticity, connectomics, neurodegeneration, or clinical neurological questions.

Cross-species genetic analysis using model organism databases. Maps human genes to orthologs in mouse, fly, worm, zebrafish, yeast, and frog, then retrieves phenotypes, expression, and functional data from MGI, FlyBase, WormBase, ZFIN, SGD, and Xenbase. Use when users ask about model organisms, gene orthologs, mouse phenotypes, fly genetics, worm RNAi, zebrafish morphants, cross-species comparison, animal models for human disease, or conservation of gene function.

Comprehensive metabolomics research skill for identifying metabolites, analyzing studies, and searching metabolomics databases. Integrates HMDB (220k+ metabolites), MetaboLights, Metabolomics Workbench, and PubChem. Use when asked to identify or annotate metabolites (HMDB IDs, chemical properties, pathways), retrieve metabolomics study information from MetaboLights (MTBLS*) or Metabolomics Workbench (ST*), search for studies by keywords or disease, or generate comprehensive metabolomics research reports.

Production-ready genomics and epigenomics data processing for BixBench questions. Handles methylation array analysis (CpG filtering, differential methylation, age-related CpG detection, chromosome-level density), ChIP-seq peak analysis (peak calling, motif enrichment, coverage stats), ATAC-seq chromatin accessibility, multi-omics integration (expression + methylation correlation), and genome-wide statistics. Pure Python computation (pandas, scipy, numpy, pysam, statsmodels) plus ToolUniverse annotation tools (Ensembl, ENCODE, SCREEN, JASPAR, ReMap, RegulomeDB, ChIPAtlas). Supports BED, BigWig, methylation beta-value matrices, Illumina manifest files, and multi-sample clinical data. Use when processing methylation data, ChIP-seq peaks, ATAC-seq signals, or answering questions about CpG sites, differential methylation, chromatin accessibility, histone marks, or epigenomic statistics.

Drug regulatory and approval research -- FDA substance registry lookup, drug classification by ATC/EPC/MoA via RxClass, Orange Book generic availability and patent status, DailyMed label parsing (adverse reactions, dosing, contraindications), and clinical trial search. Use when users ask about FDA-approved drugs, drug regulatory status, generic availability, patent expiration, drug class membership, drug labeling, or substance identification.

Create new scientific tools for ToolUniverse framework with proper structure, validation, and testing. Use when users need to add tools to ToolUniverse, implement new API integrations, create tool wrappers for scientific databases/services, expand ToolUniverse capabilities, or follow ToolUniverse contribution guidelines. Supports creating tool classes, JSON configurations, validation, error handling, and test examples.