Perform comprehensive exploratory data analysis on scientific data files across 200+ file formats. This skill should be used when analyzing any scientific data file to understand its structure, content, quality, and characteristics. Automatically detects file type and generates detailed markdown reports with format-specific analysis, quality metrics, and downstream analysis recommendations. Covers chemistry, bioinformatics, microscopy, spectroscopy, proteomics, metabolomics, and general scientific data formats.

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 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.

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.

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.

Production-ready RNA-seq differential expression analysis using PyDESeq2. Performs DESeq2 normalization, dispersion estimation, Wald testing, LFC shrinkage, and result filtering. Handles multi-factor designs, multiple contrasts, batch effects, and integrates with gene enrichment (gseapy) and ToolUniverse annotation tools (UniProt, Ensembl, OpenTargets). Supports CSV/TSV/H5AD input formats and any organism. Use when analyzing RNA-seq count matrices, identifying DEGs, performing differential expression with statistical rigor, or answering questions about gene expression changes.

Analyze mass spectrometry proteomics data including protein quantification, differential expression, post-translational modifications (PTMs), and protein-protein interactions. Processes MaxQuant, Spectronaut, DIA-NN, and other MS platform outputs. Performs normalization, statistical analysis, pathway enrichment, and integration with transcriptomics. Use when analyzing proteomics data, comparing protein abundance between conditions, identifying PTM changes, studying protein complexes, integrating protein and RNA data, discovering protein biomarkers, or conducting quantitative proteomics experiments.

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 and interpret polygenic risk scores (PRS) for complex diseases using GWAS summary statistics. Calculates genetic risk profiles, interprets PRS percentiles, and assesses disease predisposition across conditions including type 2 diabetes, coronary artery disease, and Alzheimer's disease. Use when asked to calculate polygenic risk scores, interpret genetic risk for complex diseases, build custom PRS from GWAS data, or answer questions like "What is my genetic predisposition to breast cancer?"

Production-ready phylogenetics and sequence analysis skill for alignment processing, tree analysis, and evolutionary metrics. Computes treeness, RCV, treeness/RCV, parsimony informative sites, evolutionary rate, DVMC, tree length, alignment gap statistics, GC content, and bootstrap support using PhyKIT, Biopython, and DendroPy. Performs NJ/UPGMA/parsimony tree construction, Robinson-Foulds distance, Mann-Whitney U tests, and batch analysis across gene families. Integrates with ToolUniverse for sequence retrieval (NCBI, UniProt, Ensembl) and tree annotation. Use when processing FASTA/PHYLIP/Nexus/Newick files, computing phylogenetic metrics, comparing taxa groups, or answering questions about alignments, trees, parsimony, or molecular evolution.

Comprehensive multi-omics disease characterization integrating genomics, transcriptomics, proteomics, pathway, and therapeutic layers for systems-level understanding. Produces a detailed multi-omics report with quantitative confidence scoring (0-100), cross-layer gene concordance analysis, biomarker candidates, therapeutic opportunities, and mechanistic hypotheses. Uses 80+ ToolUniverse tools across 8 analysis layers. Use when users ask about disease mechanisms, multi-omics analysis, systems biology of disease, biomarker discovery, or therapeutic target identification from a disease perspective.

Integrate and analyze multiple omics datasets (transcriptomics, proteomics, epigenomics, genomics, metabolomics) for systems biology and precision medicine. Performs cross-omics correlation, multi-omics clustering (MOFA+, NMF), pathway-level integration, and sample matching. Coordinates ToolUniverse skills for expression data (RNA-seq), epigenomics (methylation, ChIP-seq), variants (SNVs, CNVs), protein interactions, and pathway enrichment. Use when analyzing multi-omics datasets, performing integrative analysis, discovering multi-omics biomarkers, studying disease mechanisms across molecular layers, or conducting systems biology research that requires coordinated analysis of transcriptome, genome, epigenome, proteome, and metabolome data.

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.

Comprehensive immune repertoire analysis for T-cell and B-cell receptor sequencing data. Analyze TCR/BCR repertoires to assess clonality, diversity, V(D)J gene usage, CDR3 characteristics, convergence, and predict epitope specificity. Integrate with single-cell data for clonotype-phenotype associations. Use for adaptive immune response profiling, cancer immunotherapy research, vaccine response assessment, autoimmune disease studies, or repertoire diversity analysis in immunology research.

Discover genes associated with diseases and traits using GWAS data from the GWAS Catalog (500,000+ associations) and Open Targets Genetics (L2G predictions). Identifies genetic risk factors, prioritizes causal genes via locus-to-gene scoring, and assesses druggability. Use when asked to find genes associated with a disease or trait, discover genetic risk factors, translate GWAS signals to gene targets, or answer questions like "What genes are associated with type 2 diabetes?"

Compare GWAS studies, perform meta-analyses, and assess replication across cohorts. Integrates NHGRI-EBI GWAS Catalog and Open Targets Genetics to compare study designs, effect sizes, ancestry diversity, and heterogeneity statistics. Use when comparing GWAS studies for a trait, performing meta-analysis of genetic loci, assessing replication across cohorts, or exploring the genetic architecture of complex diseases.

Transform GWAS signals into actionable drug targets and repurposing opportunities. Performs locus-to-gene mapping, target druggability assessment, existing drug identification, safety profile evaluation, and clinical trial matching. Use when discovering drug targets from GWAS data, finding drug repurposing opportunities from genetic associations, or translating GWAS findings into therapeutic leads.

Perform comprehensive gene enrichment and pathway analysis using gseapy (ORA and GSEA), PANTHER, STRING, Reactome, and 40+ ToolUniverse tools. Supports GO enrichment (BP, MF, CC), KEGG, Reactome, WikiPathways, MSigDB Hallmark, and 220+ Enrichr libraries. Handles multiple ID types (gene symbols, Ensembl, Entrez, UniProt), multiple organisms (human, mouse, rat, fly, worm, yeast), customizable backgrounds, and multiple testing correction (BH, Bonferroni). Use when users ask about gene enrichment, pathway analysis, GO term enrichment, KEGG pathway analysis, GSEA, over-representation analysis, functional annotation, or gene set analysis.

Retrieves gene expression and omics datasets from ArrayExpress and BioStudies with gene disambiguation, experiment quality assessment, and structured reports. Creates comprehensive dataset profiles with metadata, sample information, and download links. Use when users need expression data, omics datasets, or mention ArrayExpress (E-MTAB, E-GEOD) or BioStudies (S-BSST) accessions.

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.