Tooluniverse

Microbiome and metagenomics analysis using MGnify, GTDB taxonomy, ENA sequencing data, and EuropePMC literature. Covers taxonomic classification, genome quality assessment, biome-clinical phenotype linkage, and pathway interpretation. Use for amplicon/shotgun metagenomics study analysis.

Analyze NIH grant portfolios and funding history using the OpenNIH FY1985-present corpus, then connect grants to investigators, institutions, publications, clinical trials, patents, targets, or drugs with ToolUniverse. Use for NIH grant discovery, topic or Institute/Center trends, PI and institution profiles, activity-code or mechanism analysis, funding growth and concentration, grant-writing landscape research, SBIR/STTR landscapes, research-policy analysis, expert discovery, funding-to-output translational impact studies, or public-facing NIH explainers for patients, advocates, local and national journalists, trainees, applicants, institutions, entrepreneurs, and taxpayers.

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.

Rare disease genomics — disease identification (Orphanet), causative gene discovery, gene-disease validity (GenCC), variant interpretation (ClinVar), and translational research (ClinicalTrials.gov, drug repurposing for orphans). Use for rare-disease-gene curation, novel-gene-discovery analysis, and rare-disease drug-development support.

Structural biology plus proteomics integration for drug target validation. Combines PDB experimental structures, AlphaFold predictions, GPCRdb, SAbDab antibody structures, ProteinsPlus binding-site prediction, and BindingDB ligand-affinity data. Use for druggability assessment, binding-site characterization, ligand-pocket analysis, structural-confidence scoring (resolution, pLDDT), and antibody-target interface analysis.

Answer biomedical FACTUAL / recall / multiple-choice questions by querying ToolUniverse database tools instead of answering from memory. Triggers on any 'which gene/drug/variant/disease/pathway/miRNA/TF...' lookup, any question phrased 'according to <database>' (DisGeNet, OMIM, MSigDB, miRDB, GTRD, MGI, Ensembl, ClinVar, ChEMBL, OpenTargets, Reactome, GtoPdb, UniProt...), and multiple-choice biology/medicine knowledge questions where one option must be verified against an authoritative source. NOT for analyzing user-supplied data files (CSV/VCF/h5ad → use the data-analysis router) and NOT for open-ended literature synthesis. Use whenever a single correct answer exists in a public biomedical database and could be looked up rather than guessed.

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.

Quantitative drug-target validation pipeline. Scores druggability, selectivity, safety profile, ADMET feasibility, and structural tractability with a composite Target Validation Score (0-100) and GO/NO-GO recommendation. Use for go/no-go decisions on a target before commit-to-medchem, target prioritization across a list, and target-deselection rationale.

Rare disease differential diagnosis from patient phenotype — HPO term matching to candidate diseases (Orphanet, OMIM), gene panel prioritization, ACMG variant interpretation, and structure-based variant analysis. Use for diagnostic odyssey assistance, phenotype-to-disease ranking, and genetic-counseling differential generation.

Spatial multi-omics interpretation pipeline. Transforms spatially variable genes (SVGs), domain annotations, and tissue context into biological insights via domain-by-domain characterization, cell-type composition, spatial gene expression patterns, RNA+protein+metabolite integration. Use for Visium, MERFISH, seqFISH, Slide-seq, spatial proteomics, and spatial multi-omics interpretation. Goes beyond statistics to disease mechanisms and therapeutic opportunities.

Clinical variant interpretation from raw variant calls to ACMG-classified recommendations with structural impact analysis. Use for VUS classification, pathogenicity assessment with cited criteria, structure-based variant impact (AlphaFold/PDB), non-coding/regulatory variant effect prediction with sequence deep-learning models (AlphaGenome, Enformer, Borzoi, ChromBPNet, Evo 2), and producing clinical-grade variant reports for return of results or molecular tumor boards. Use this whenever a user asks about a variant's significance, an intronic/promoter/enhancer/UTR non-coding variant's functional impact, or needs ACMG classification — even if they don't say "ACMG".

Detect and analyze adverse drug event signals using FDA FAERS reports, drug labels, and disproportionality statistics (PRR, ROR, IC). Generates quantitative safety signal scores (0-100) with evidence grading. Use for post-market surveillance, pharmacovigilance, drug safety assessment, regulatory submissions, and detecting rare AE signals not visible in clinical trials.

Map environmental and industrial chemicals to adverse outcome pathways (AOPs) — molecular initiating event to organ-level toxicity. Uses AOPWiki, GHS classification, IARC carcinogen status, and LD50 data. Use for environmental/industrial chemical risk assessment, regulatory-grade hazard characterization, and AOP stressor mapping. Distinct from drug-safety analysis (use tooluniverse-pharmacovigilance for drugs).

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.

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.

Interpret a single GWAS SNP across multiple databases — GWAS Catalog hits, LD/haplotype context, eQTL evidence, regulatory annotation, ClinVar pathogenicity, gnomAD frequency. Use for 'what does this SNP do', SNP-to-mechanism tracing, and resolving lead-SNP-vs-causal-variant ambiguity. Always considers LD structure before claiming a SNP is mechanistically responsible.

Mendelian randomization (MR) causal inference — does an exposure, risk factor, or biomarker CAUSALLY affect a disease/outcome, using genetic variants as instrumental variables (IEU OpenGWAS / EpiGraphDB MR-EvE). Use this whenever the user asks if X causes Y, whether an observational association is actually causal or just correlation, if a biomarker/trait is a causal risk factor, wants to triangulate epidemiology against genetic evidence, or mentions Mendelian randomization, instrumental-variable analysis, two-sample MR, or genetic causal evidence — even if they never say "MR" (e.g. "is LDL cholesterol actually causal for heart disease?", "does BMI cause type 2 diabetes or just correlate?", "is CRP a causal driver of stroke?"). Covers trait-label resolution, MR effect direction/magnitude, instrument quality (MOE score), method agreement (IVW vs MR-Egger vs weighted median), bidirectional MR for reverse causation, and distinguishing causation from genetic correlation. Not for plain GWAS association lookups (use

Cross-species genetic analysis using model organism databases (MGI mouse, ZFIN zebrafish, FlyBase fruit fly, WormBase worm, SGD yeast, RGD rat, GBIF taxonomy). Maps human genes to orthologs, retrieves phenotype/expression/functional data, assesses gene function conservation, and identifies the best animal model for studying a human gene or disease.

Multi-omics integration — orchestrate per-layer analysis (transcriptomics, proteomics, epigenomics, genomics, metabolomics) then perform cross-omics correlation, multi-omics clustering, and pathway-level integration. Use for integrative systems-biology analysis, multi-modal disease characterization, and cross-omics biomarker discovery.

Spatial transcriptomics analysis — Visium, MERFISH, seqFISH, Slide-seq. Maps gene expression to tissue architecture, identifies spatially variable genes (SVGs), tissue-domain segmentation, and cell-cell interaction inference. Use for spatial gene-expression questions, tissue architecture analysis, and SVG identification.

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.

End-to-end observational epidemiology analysis — from research question (PECO Population/Exposure/Comparator/Outcome) to publication-ready statistical report. Covers cohort/case-control/cross-sectional design, regression with confounders, propensity scoring, sensitivity analysis. Writes Python code for every step. Use for epidemiology study analysis, NHANES/UK-Biobank-style analyses.

Gene-disease association analysis across DisGeNET, OpenTargets, Monarch, OMIM, GenCC, Orphanet. Cross-references multiple sources for evidence-graded association reports with concordance scoring (5/5 sources agree → strong, 1/5 → weak). Use for 'which diseases is gene X associated with' or 'which genes cause disease Y' queries with quantitative confidence.

Gene regulatory network analysis — TF-target inference (JASPAR motifs, ChIP-seq), motif scanning, eQTL integration, perturbation evidence (knockout/overexpression). Use for 'which TF regulates gene X', 'which genes does TF Y target', regulatory pathway reconstruction. Distinguishes direct (binding) vs indirect (co-expression) regulatory evidence.

Deep literature review — PubMed, EuropePMC, bioRxiv preprints, citation networks, evidence synthesis. Disambiguates queries, runs collision-aware searches, grades evidence T1-T4, and produces structured reports. Use for systematic literature review, meta-analysis evidence collection, and detailed answer-with-citations workflows.

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.

Small molecule identification, characterization, and procurement — PubChem, ChEMBL, BindingDB, ADMET-AI, SwissADME, eMolecules, Enamine. Covers compound name to structure to activity to ADMET properties to commercial sourcing. Use for chemical biology, lead identification, probe selection, and the full small-molecule discovery pipeline.

End-to-end drug safety review integrating FDA labels, FAERS adverse event reports, PRR/ROR disproportionality, pharmacogenomic biomarkers, clinical trial data, and published literature. Use for regulatory drug safety reviews, comprehensive pharmacovigilance reports, label-vs-real-world AE comparison, and clinical decision support for drug safety.

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.

Retrieve gene expression and omics datasets from ArrayExpress and BioStudies with gene disambiguation and quality assessment. Use for finding RNA-seq/microarray datasets by organism/tissue/condition, comparing across studies (case-control, time-series, dose-response), and assessing dataset suitability before downloading. Always uses English search terms.

Find and retrieve proteomics datasets from MassIVE and ProteomeXchange. Search by species, keyword, or accession; retrieve detailed metadata (instruments, publications, species, PTMs studied). Use for locating public proteomics datasets to reanalyze, comparing instrument/protocol coverage across studies, and pre-download dataset evaluation.

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.

TCR/BCR repertoire analysis — V(D)J segment usage, CDR3 sequence diversity, clonality scoring, antigen specificity matching to IEDB, public-clone identification. Use for adaptive immune response characterization, post-treatment immune monitoring, antigen-specific clone tracking, and clonal-expansion analysis in immunotherapy or vaccination studies.

AI-guided de novo protein design — RFdiffusion backbone generation, ProteinMPNN sequence design, structure validation (pLDDT, pTM, MPNN scores). Use for designing therapeutic protein binders, novel scaffolds, enzyme variants, and miniprotein/protein-interface design before experimental validation.

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).

Systematic ACMG/AMP germline variant classification with all 28 criteria (PVS1, PS1-4, PM1-6, PP1-5, BA1, BS1-4, BP1-7) for clinical significance. Produces 5-tier verdict (Pathogenic / Likely Pathogenic / VUS / Likely Benign / Benign) with cited evidence per criterion. Use for variant interpretation, VUS resolution, and pathogenicity assessment. Combines ClinVar, gnomAD, computational predictors, and gene-mechanism context.

Retrieve chemical compound data from PubChem and ChEMBL with disambiguation, cross-referencing, and stereochemistry handling. Use for resolving compound names to SMILES/InChI/CID/ChEMBL IDs (including OPSIN deterministic IUPAC-name-to-structure parsing), fetching molecular properties, distinguishing isomers/stereo forms, and cross-validating identity across databases. Always use English compound names; flags ambiguous queries (e.g., Vitamin D has multiple forms).

Interpret hits from CRISPR-KO/CRISPRi/shRNA screens by integrating DepMap essentiality, gnomAD constraint scores, pathway context (Reactome, STRING), druggability (DGIdb), and clinical evidence (CIViC, COSMIC). Use for screen-hit prioritization, essentiality ranking, and turning a list of screen hits into a prioritized target shortlist.

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 / IC) or drug-AE associatio

Protein structure retrieval from RCSB PDB, PDBe, and AlphaFold with disambiguation, quality assessment (resolution, R-factor, pLDDT), and metadata. Distinguishes high-quality experimental (X-ray under 2 Angstrom) vs predicted vs medium-quality structures. Use for fetching protein structures, structure-quality comparison, and selecting structures for drug design or modeling.

Non-coding/regulatory variant interpretation — GWAS association lookup, eQTL evidence (GTEx), chromatin state (ENCODE), regulatory variant scoring (RegulomeDB, CADD), and TF-binding disruption. Use for non-coding GWAS hit interpretation, eQTL-based gene assignment, and regulatory mechanism reasoning. Distinct from coding-variant tools.

Structural variant (SV) clinical interpretation: deletions, duplications, inversions, translocations, complex rearrangements. Applies ACMG-adapted criteria with ClinGen HI/TS dosage scores, gnomAD frequencies, and ClinVar evidence. Produces 5-tier classification with explicit per-criterion evidence. Use for clinical genomics SV review, dosage-sensitivity assessment, breakpoint analysis, and CNV pathogenicity calls. Gene-dosage-driven reasoning.

GPCR receptor pharmacology — agonist/antagonist/inverse-agonist/biased-agonist classification, GPCRdb structural data, receptor-ligand binding analysis, antibody-target interface (SAbDab). Use for GPCR drug discovery, biased-agonism analysis, receptor subtype selectivity questions, and orthosteric vs allosteric pocket characterization.

Inorganic chemistry, physical chemistry, and materials science — crystal structures, coordination chemistry, lattice parameters, thermodynamic properties, electronic structure. Use for unit cell volume calculations, coordination geometry, materials property estimation, and inorganic-mechanism reasoning. Complementary to tooluniverse-organic-chemistry.

Protein 3D structure prediction from sequence — ESMFold de novo prediction, AlphaFold database retrieval, experimental structures from RCSB, ProtVar variant impact assessment, ProtParam sequence properties. Use for structure prediction when no experimental structure exists, fold-confidence scoring, and structure-guided variant interpretation.

FASTQ quality control and adapter/quality-trimming decisions with local NGS tools — run FastQC on raw reads, summarize a project with MultiQC, interpret per-base sequence quality, per-base N content, adapter content, overrepresented sequences, sequence duplication and GC content, and decide whether (and how) to trim with fastp / Cutadapt before downstream analysis. seqkit for read counts/stats/subsampling. Use when someone asks "run QC on my FASTQs", "are my reads good quality?", "do I need to trim adapters?", "interpret this FastQC report", "what does this WARN/FAIL mean", "why are overrepresented sequences flagged", "should I quality-trim before alignment", "make a MultiQC summary", or "clean up these reads with fastp". NOT for differential expression / DEG analysis (use tooluniverse-rnaseq-deseq2), NOT for read alignment, coverage, or variant calling (use tooluniverse-variant-analysis / tooluniverse-sequence-analysis). Honest: shells out to real local binaries; if a tool is missing...

Clinical interpretation of somatic cancer mutations for precision oncology. Transforms a gene + variant + cancer-type input into an actionable report: clinical evidence tier (CIViC, OncoKB), therapeutic options (FDA-approved + investigational), resistance mechanisms, prognosis, and matching clinical trials. Use for tumor-board variant calls, somatic-mutation actionability assessment, and treatment selection. Always cancer-type-specific.

Dereplicate a putative natural product and assign its chemical taxonomy. Use to answer "is [compound] a known natural product", "what microbe/organism produces [compound]", "what chemical class is [compound]", "dereplicate this metabolite (by formula/exact mass/InChIKey/SMILES)", or "classify this molecule into ChemOnt". Searches NPAtlas for known microbial natural products (producing organism + literature reference), assigns the ChemOnt kingdom→superclass→class→subclass hierarchy via ClassyFire, resolves systematic IUPAC names to structure via OPSIN, and cross-references identity in PubChem. NOT for general drug/compound identity or ADMET (use tooluniverse-chemical-compound-retrieval / tooluniverse-small-molecule-discovery) and NOT for metabolomics pathway/enrichment analysis (use tooluniverse-metabolomics skills).

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.

Functional annotation of protein variants — ProtVar structural/functional context, ClinVar clinical classifications, gnomAD population frequencies, CADD deleteriousness, ClinGen gene-disease validity, plus FAVOR one-call comprehensive GRCh38 annotation. Use for variant annotation pipelines, missense effect prediction, and protein-level variant interpretation with functional context.

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.

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).

Validate a variant-effect predictor (AlphaMissense, ESM-C SAE, ESM logits, EVE, conservation scores, or any per-variant numeric score) against experimental deep mutational scanning (DMS) data. Computes per-variant predictor scores, splits variants into neutral vs disruptive groups by DMS effect, runs a Mann-Whitney U test on the predictor scores, and sweeps the stratification thresholds for robustness. Use when you need to know whether a predictor's scores track real functional disruption on a specific protein.

Predict patient response to immune checkpoint inhibitors (ICIs) by integrating tumor mutational burden (TMB), microsatellite instability (MSI), PD-L1 expression, HLA status, and immune-related gene expression. Outputs ICI Response Score with drug-specific recommendations and resistance-risk assessment. Use for melanoma/NSCLC/RCC immunotherapy decision support.

Genome-ASSEMBLY discovery, QC, and replicon mapping for any organism (bacteria, archaea, fungi, and beyond) using NCBI Datasets. Resolves an organism name or taxid to assemblies, picks the reference/representative or best-quality assembly, pulls assembly QC metrics (total length, contig/scaffold N50, contig count, GC%, assembly level, RefSeq category), enumerates chromosomes and plasmids via per-replicon sequence reports, and compares candidate assemblies on quality. Use for "what genomes are available for [organism]", "assembly stats / N50 / GC content for [GCF_/GCA_ accession]", "how many plasmids does [strain] have", "compare assemblies for [species]", "find the reference genome for [taxon]", "is this assembly Complete Genome or just contigs". NOT for gene-level orthology/synteny (use tooluniverse-comparative-genomics), plant gene structure (use tooluniverse-plant-genomics), de novo assembly from raw reads (no tool exists), or taxonomy-only name/lineage lookups.

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.

Given a PDB structure, produce a per-residue annotation table: which residues sit at a binding interface (vs a partner chain), which line a ligand pocket, which are buried (core) vs solvent-exposed (surface), and optionally secondary structure. This is the structural track drawn under a DMS heatmap and the structural prior SAE feature drops are read against. Use when you need to anchor a variant-interpretation or DMS analysis to the protein's actual physical context.

Comprehensive disease characterization across genomics, transcriptomics, proteomics, and pathways for systems-level understanding. Identifies therapeutic opportunities and biomarker candidates by integrating multi-layer molecular data. Use for full-omics disease deep-dive reports, mechanism mapping, and biomarker-and-target identification from multi-omics data.

Interpret a missense variant via ESMC-6B Sparse Autoencoder (SAE) feature activations. For a given protein + variant, computes which interpretable SAE features (catalytic, ligand-binding, PTM, structural motif, domain, etc.) are lost or gained at the mutation site. Use when standard pathogenicity scores (AlphaMissense, ClinVar) say a variant is damaging but you need a MECHANISTIC explanation — e.g. 'why is this variant LoF?' Complements (does not replace) variant-interpretation and variant-to-mechanism skills, which focus on ACMG classification or regulatory mechanism.

Retrieve DNA/RNA/protein sequences from NCBI and ENA with disambiguation. Quality hierarchy: RefSeq (NM_/NP_) > RefSeq predicted (XM_/XP_) > GenBank submissions. Use for fetching specific sequences by accession, gene-symbol-to-sequence lookup, transcript-isoform retrieval, and curated-vs-raw-submission preference.