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1. ▌
   Tooluniverse Variant To Mechanism · mims-harvard

   End-to-end variant-to-mechanism analysis — trace a variant (rsID/coordinates) through regulatory context, target gene(s), molecular pathway(s), and phenotypic consequences. Integrates 7+ databases across 3 evidence layers (regulatory, molecular, disease) for a mechanistic model. Use for GWAS-hit-to-mechanism, eQTL-causal-gene tracing, and full causal-chain reports.
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   Setup Transcriptformer Remote Tool · mims-harvard bundle

   Set up, launch, validate, and troubleshoot the TranscriptFormer ToolUniverse remote tool and optionally relay it through ToolUniverse Connect. Use when deploying or auditing this implementation.
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   Setup Uspto Downloader Remote Tool · mims-harvard bundle

   Set up, launch, validate, and troubleshoot the USPTO downloader ToolUniverse remote tool and optionally relay it through ToolUniverse Connect. Use when deploying or auditing this implementation.
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   Tooluniverse Cancer Classification · mims-harvard

   Translate free-text tumor descriptions to OncoTree codes and resolve cancer subtypes/tissue hierarchy. Cross-references UMLS/NCI vocabularies. Use for standardizing cancer-type nomenclature in EHR free-text, building cohorts in OncoKB or GDC, mapping tumor-board notes to ontology codes, and ensuring consistent terminology across cancer-genomics pipelines.
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   Tooluniverse Clinical Risk Scoring · mims-harvard bundle

   Compute and interpret validated bedside clinical risk scores and pretest probabilities for an INDIVIDUAL patient — pick the right score for the scenario, gather inputs, run the deterministic calculator tool, and read the result against an interpretation table. Covers CHA2DS2-VASc (AF stroke risk), HAS-BLED (bleeding on anticoagulation), CURB-65 (pneumonia severity / admit decision), qSOFA (sepsis screen), Child-Pugh + MELD-Na (cirrhosis severity / transplant priority), Wells DVT and Wells PE (VTE pretest probability), ASCVD (10-year cardiovascular risk / statin decision), and eGFR CKD-EPI (kidney function / drug dosing). Use when asked things like "stroke risk for this AF patient", "should this patient be anticoagulated", "pneumonia severity — admit or not?", "sepsis screen this patient", "DVT/PE pretest probability", "10-year cardiovascular risk", "cirrhosis severity / MELD score", or "eGFR / kidney function". Pairs CHA2DS2-VASc with HAS-BLED to weigh anticoagulation. NOT for polygenic/genetic risk (use tool
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6. ▌
   Tooluniverse Clinical Trial Design · mims-harvard bundle

   Strategic clinical trial design feasibility assessment. Analyzes 6 dimensions (endpoint, population, comparator, effect size, duration, regulatory pathway) using precedent trials and FDA guidance. Produces enrollment projections, endpoint recommendations, and approval-pathway analysis. Use for trial-protocol design, power/sample-size estimation, comparator selection, and FDA submission strategy. Driven by precedent-based reasoning rather than first-principles math.
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   Tooluniverse Drug Drug Interaction · mims-harvard bundle

   Assess drug-drug interactions — CYP metabolic interactions (substrate/inhibitor/inducer), transporter (P-gp, BCRP, OATP) effects, pharmacodynamic synergy/antagonism, clinical significance scoring, and management recommendations. Use for polypharmacy review, prescribing decision support, and safety analysis when adding or switching drugs.
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8. ▌
   Tooluniverse Epigenomics Chromatin · mims-harvard

   Histone-modification ChIP-seq, ATAC-seq accessibility, chromatin state, and TF binding analysis from ENCODE, Roadmap Epigenomics, ChIP-Atlas. Use for chromatin-state-by-tissue queries, TF-binding-by-region, regulatory landscape mapping, and ENCODE-cCRE annotations. For DNA methylation use tooluniverse-epigenomics; for RNA-seq use tooluniverse-rnaseq-deseq2.
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   Tooluniverse Metabolomics Analysis · mims-harvard bundle

   Analyze metabolomics data end-to-end — metabolite identification, quantification (TIC normalization, batch correction), differential analysis, and pathway interpretation. Use for processing mass-spec metabolomics output, normalization choice, untargeted metabolomics workflows, and integrating with other omics layers.
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10. ▌
    Tooluniverse Metagenomics Analysis · mims-harvard

    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.
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11. ▌
    Tooluniverse Nih Funding Landscape · mims-harvard bundle

    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.
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12. ▌
    Tooluniverse Protein Lof Mechanism · mims-harvard

    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.
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13. ▌
    Tooluniverse Rare Disease Genomics · mims-harvard

    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.
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14. ▌
    Tooluniverse Structural Proteomics · mims-harvard

    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.
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    Tooluniverse Biomedical Fact Lookup · mims-harvard bundle

    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.
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    Tooluniverse Crispr Screen Analysis · mims-harvard bundle

    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.
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17. ▌
    Tooluniverse Drug Target Validation · mims-harvard bundle

    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.
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    Tooluniverse Rare Disease Diagnosis · mims-harvard bundle

    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.
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    Tooluniverse Spatial Omics Analysis · mims-harvard bundle

    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.
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20. ▌
    Tooluniverse Variant Interpretation · mims-harvard bundle

    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".
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21. ▌
    Tooluniverse Adverse Event Detection · mims-harvard bundle

    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.
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22. ▌
    Tooluniverse Adverse Outcome Pathway · mims-harvard

    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).
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23. ▌
    Tooluniverse Clinical Trial Matching · mims-harvard bundle

    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.
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24. ▌
    Tooluniverse Drug Mechanism Research · mims-harvard

    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.
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25. ▌
    Tooluniverse Gwas Snp Interpretation · mims-harvard bundle

    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.
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26. ▌
    Tooluniverse Mendelian Randomization · mims-harvard bundle

    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
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27. ▌
    Tooluniverse Model Organism Genetics · mims-harvard

    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.
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28. ▌
    Tooluniverse Multi Omics Integration · mims-harvard bundle

    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.
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    Tooluniverse Spatial Transcriptomics · mims-harvard bundle

    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.
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30. ▌
    Tooluniverse Molecular Cloning · mims-harvard bundle

    Molecular cloning assembly design — Gibson Assembly (overlap design for seamless multi-fragment joining) and Golden Gate Assembly (Type IIS / BsaI / BbsI design with unique 4-bp fusion overhangs). Use when you need to plan how to join DNA fragments into a construct, design assembly overlaps/overhangs, or decide between cloning methods. Covers the domestication (internal-site removal), overhang-uniqueness, and overlap-Tm rules. For PCR primers to generate the fragments, see tooluniverse-primer-design.
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31. ▌
    Tooluniverse Computational Biophysics · mims-harvard bundle

    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.
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32. ▌
    Tooluniverse Epidemiological Analysis · mims-harvard

    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.
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33. ▌
    Tooluniverse Gene Disease Association · mims-harvard

    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.
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    Tooluniverse Gene Regulatory Networks · mims-harvard

    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.
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    Tooluniverse Literature Deep Research · mims-harvard bundle

    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.
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36. ▌
    Tooluniverse Pathway Disease Genetics · mims-harvard

    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.
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37. ▌
    Tooluniverse Small Molecule Discovery · mims-harvard

    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.
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38. ▌
    Tooluniverse Clinical Data Integration · mims-harvard

    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.
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39. ▌
    Tooluniverse Data Integration Analysis · mims-harvard

    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.
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40. ▌
    Tooluniverse Expression Data Retrieval · mims-harvard bundle

    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.
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41. ▌
    Tooluniverse Proteomics Data Retrieval · mims-harvard

    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.
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42. ▌
    Tooluniverse Diagnostic Test Evaluation · mims-harvard bundle

    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.
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43. ▌
    Tooluniverse Immune Repertoire Analysis · mims-harvard bundle

    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.
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44. ▌
    Tooluniverse Protein Therapeutic Design · mims-harvard bundle

    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.
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45. ▌
    Tooluniverse Phewas · mims-harvard

    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).
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46. ▌
    Tooluniverse Acmg Variant Classification · mims-harvard

    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.
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47. ▌
    Tooluniverse Chemical Compound Retrieval · mims-harvard bundle

    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).
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48. ▌
    Tooluniverse Functional Genomics Screens · mims-harvard

    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.
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49. ▌
    Tooluniverse Product Safety Surveillance · mims-harvard bundle

    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
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50. ▌
    Tooluniverse Protein Structure Retrieval · mims-harvard bundle

    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.
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51. ▌
    Tooluniverse Regulatory Variant Analysis · mims-harvard

    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.
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    Tooluniverse Structural Variant Analysis · mims-harvard bundle

    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.
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53. ▌
    Tooluniverse Gpcr Structural Pharmacology · mims-harvard

    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.
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54. ▌
    Tooluniverse Inorganic Physical Chemistry · mims-harvard bundle

    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.
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    Tooluniverse Protein Structure Prediction · mims-harvard

    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.
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56. ▌
    Tooluniverse Fastq Qc · mims-harvard bundle

    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...
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57. ▌
    Tooluniverse Cancer Variant Interpretation · mims-harvard bundle

    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.
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58. ▌
    Tooluniverse Natural Product Dereplication · mims-harvard bundle

    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).
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59. ▌
    Tooluniverse Protein Modification Analysis · mims-harvard

    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.
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    Tooluniverse Variant Functional Annotation · mims-harvard

    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.
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61. ▌
    Tooluniverse Peptide Target Deorphanization · mims-harvard bundle

    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.
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62. ▌
    Tooluniverse Population Genetics 1000genomes · mims-harvard

    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).
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63. ▌
    Tooluniverse Variant Predictor Dms Validation · mims-harvard

    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.
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64. ▌
    Tooluniverse Immunotherapy Response Prediction · mims-harvard bundle

    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.
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65. ▌
    Tooluniverse Microbial Genome Characterization · mims-harvard bundle

    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.
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66. ▌
    Tooluniverse Precision Medicine Stratification · mims-harvard bundle

    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.
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67. ▌
    Tooluniverse Protein Structural Annotation Pdb · mims-harvard

    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.
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68. ▌
    Tooluniverse Multiomic Disease Characterization · mims-harvard bundle

    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.
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69. ▌
    Tooluniverse Protein Sae Variant Interpretation · mims-harvard

    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.
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70. ▌
    Tooluniverse Sequence Retrieval · mims-harvard bundle

    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.
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71. ▌
    Tooluniverse Residue Functional Mechanism Interpretation · mims-harvard

    Given a set of residues in a protein, explain WHY they are functionally critical by combining structural context (binding interface, ligand pocket, core, secondary structure), UniProt features (active sites, binding sites, PTM sites, disulfides), optional SAE feature evidence, and optional DMS data. Accepts residues from any source: DMS hotspots (top-K by max effect), ClinVar recurrent variants, literature-reported hot regions, evolutionarily conserved positions, or user-curated lists. Returns a per-cluster mechanism call: catalytic / ligand-binding / interface / structural-core / PTM / regulatory / unknown.
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72. ▌
    Tooluniverse Meta Analysis · mims-harvard bundle

    Meta-analysis / evidence synthesis — pool effect sizes across studies (odds ratios, risk ratios, hazard ratios, mean differences, correlations, GWAS betas) with fixed- or random-effects models, quantify heterogeneity (Q, I², τ²), and build a forest plot. Use when you have results from MULTIPLE studies and need a single pooled estimate, or to synthesize evidence from a systematic review / multiple GWAS / replicated experiments. Handles the error-prone effect-size + standard-error preparation (converting OR/HR/CI, two-group means±SD, proportions, and correlations into the (effect, SE) the pooling step needs).
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73. ▌
    Tooluniverse Noncoding Rna · mims-harvard

    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.
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74. ▌
    Tooluniverse Phylogenetics · mims-harvard bundle

    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.
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75. ▌
    Tooluniverse Primer Design · mims-harvard bundle

    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.
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76. ▌
    Tooluniverse Rnaseq Deseq2 · mims-harvard bundle

    RNA-seq differential expression analysis with DESeq2, edgeR, and limma-voom — DEG lists, fold changes, dispersion estimation, design formulas including covariates, multi-condition contrasts, and Venn-set operations across groups. Routes across DESeq2 (default), edgeR (QL-F / exact test for small replicate counts), and limma-voom (large n / complex designs). Use when you have a count matrix + metadata, want to find DEGs, or need dispersion/PCA/clustering analysis. Includes RULE ZERO precedence (read executed.ipynb if present).
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77. ▌
    Devtu Optimize Descriptions · mims-harvard bundle

    Optimize tool descriptions in ToolUniverse JSON configs for clarity and usability. Reviews descriptions for missing prerequisites, unexpanded abbreviations, unclear parameters, and missing usage guidance. Use when reviewing tool descriptions, improving API documentation, or when user asks to check if tools are easy to understand.
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78. ▌
    Setup Slingshot Remote Tool · mims-harvard bundle

    Set up, launch, validate, and troubleshoot the Slingshot ToolUniverse remote tool and optionally relay it through ToolUniverse Connect. Use when deploying or auditing this implementation.
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79. ▌
    Tooluniverse Data Wrangling · mims-harvard bundle

    Universal data access patterns for downloading and parsing scientific data when ToolUniverse tools don't cover the source, only return metadata, or you need bulk records. Use for VCF/h5ad/BAM/SDF/GCT parsing, multi-step API workflows (search to filter to download to parse), thousands of records at once, or sources with no dedicated tool. Write Python code via Bash for every step.
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80. ▌
    Tooluniverse Gene Liability · mims-harvard bundle

    Evaluate the human safety liability of knocking down, knocking out, degrading, or pharmacologically inhibiting a gene. Use for gene safety scoring, on-target toxicity assessment, essentiality and genetic-constraint review, critical-organ expression analysis, or deciding whether a target needs partial, transient, or tissue-specific modulation.
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81. ▌
    Tooluniverse Image Analysis · mims-harvard bundle

    Microscopy and quantitative imaging analysis — colony morphometry, fluorescence intensity quantification, cell-count statistics, dose-response curves, and ANOVA/Dunnett on image-derived measurements. Uses pandas/numpy/scipy/scikit-image. Use for analyzing tabular outputs from CellProfiler/ImageJ, image-derived measurement statistics, and image-based assay quantification.
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82. ▌
    Tooluniverse Install Skills · mims-harvard

    Detect and auto-install missing ToolUniverse research skills. Checks common Claude Code/Cursor/Codex skill directories for the canary file, and installs any missing skills if none found. Use when the plugin's research skills aren't loading, when migrating between clients, or when verifying a skill installation.
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83. ▌
    Tooluniverse Plant Genomics · mims-harvard

    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.
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84. ▌
    Tooluniverse Vaccine Design · mims-harvard bundle

    Computational vaccine candidate design: peptide/subunit vaccines via MHC-I/MHC-II epitope prediction (IEDB), population HLA coverage optimization, B-cell epitope identification, and cross-strain conservation analysis. Use for vaccine epitope prediction, HLA allele coverage, multi-epitope construct design, and immunogenicity assessment. Combines predicted MHC binding with experimentally validated IEDB epitopes for higher-confidence designs.
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85. ▌
    Setup Celltypist Remote Tool · mims-harvard bundle

    Set up, launch, validate, and troubleshoot the CellTypist ToolUniverse remote tool and optionally relay it through ToolUniverse Connect. Use when deploying or auditing this implementation.
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86. ▌
    Setup Chrombpnet Remote Tool · mims-harvard bundle

    Set up, launch, validate, and troubleshoot the ChromBPNet ToolUniverse remote tool and optionally relay it through ToolUniverse Connect. Use when deploying or auditing this implementation.
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87. ▌
    Tooluniverse Chemical Safety · mims-harvard bundle

    Chemical safety and toxicology assessment integrating ADMET-AI predictions, CTD toxicogenomics, PubChemTox experimental data, GHS/IARC hazard classification, and exposure-context analysis. Use for chemical hazard identification, occupational/consumer-product toxicity, dose-response evaluation, and acute (LD50) vs chronic toxicity assessment. Distinguishes drug toxicity from environmental chemical toxicity.
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88. ▌
    Tooluniverse Drug Regulatory · mims-harvard

    Drug regulatory and approval research — FDA substance registry, ATC/EPC classification, EMA decisions, generic-drug status, FDA Orange Book exclusivity, NDA/BLA pathways. Use for jurisdiction-aware approval status (FDA vs EMA), generic vs brand availability, exclusivity expiry tracking, and regulatory pathway selection. Always specifies the market when reporting status.
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89. ▌
    Tooluniverse Enzyme Kinetics · mims-harvard bundle

    Enzyme kinetics — Michaelis-Menten Km, Vmax, kcat (turnover), and kcat/Km (catalytic efficiency / specificity constant) from substrate-velocity data, plus inhibition-mechanism analysis (competitive / uncompetitive / non-competitive, Ki). Fits the MM equation by nonlinear regression (and reports Lineweaver-Burk for reference). Use when you have substrate concentrations and initial reaction velocities and need kinetic parameters or to classify an inhibitor. NOT for BRENDA database lookups of published constants (use the BRENDA tools).
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90. ▌
    Tooluniverse Gene Enrichment · mims-harvard bundle

    Gene-set enrichment analysis — GO (Biological Process, Molecular Function, Cellular Component), KEGG, Reactome pathway enrichment via clusterProfiler, gseapy, ORA, GSEA. Use for interpreting DEG lists, screen hit lists, or any gene-list-to-pathways query. Includes simplify-cutoff handling and union-vs-total denominator conventions for percent-DE questions.
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91. ▌
    Tooluniverse Systems Biology · mims-harvard bundle

    Systems biology and pathway analysis integrating Reactome, KEGG, WikiPathways, BioCarta, NCI-Nature Pathway Interaction Database. Multi-database pathway enrichment, protein-pathway relationships, network reasoning. Use for pathway analysis on a gene list, multi-source pathway concordance, and systems-level interpretation across databases.
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92. ▌
    Tooluniverse Target Research · mims-harvard bundle

    Comprehensive drug-target intelligence — tissue expression (GTEx, HPA), pathways, protein interactions (STRING), variant landscape (ClinVar, gnomAD), druggability (DGIdb, ChEMBL approved drugs). 9 parallel research paths with citations. Use for full target profile reports, target characterization for drug discovery, and 'tell me about target X' queries.
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93. ▌
    Setup Depmap 24q2 Remote Tool · mims-harvard bundle

    Set up, launch, validate, and troubleshoot the DepMap 24Q2 ToolUniverse remote tool and optionally relay it through ToolUniverse Connect. Use when deploying or auditing this implementation.
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94. ▌
    Tooluniverse Admet Prediction · mims-harvard

    Comprehensive ADMET (Absorption, Distribution, Metabolism, Excretion, Toxicity) profiling for drug candidates. Integrates ADMET-AI predictions, SwissADME drug-likeness, PubChemTox experimental toxicity, ChEMBL clinical data, Lipinski rule-of-five, and CYP interaction data. Use for drug-likeness assessment, BBB penetration, bioavailability, hepatotoxicity prediction, ADME/PK profiling, or screening compound libraries before lab testing.
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95. ▌
    Tooluniverse Aging Senescence · mims-harvard

    Aging biology, cellular senescence, and longevity research. Covers senescence markers (p16/CDKN2A, SASP, SA-beta-gal), aging hallmarks, senolytic drug discovery (dasatinib+quercetin, fisetin, navitoclax), epigenetic clocks, telomere biology, and longevity GWAS. Use for senescence-pathway analysis, age-related disease genetics, senolytic-target discovery, and centenarian-genetics queries. Distinguishes correlative vs causal evidence (knockout, intervention).
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96. ▌
    Tooluniverse Binder Discovery · mims-harvard bundle

    Discover novel small-molecule binders for protein targets using structure-based and ligand-based screening. Covers druggability assessment, known-ligand mining (ChEMBL, BindingDB), similarity expansion, ADMET filtering, and synthesis feasibility. Use for hit identification, virtual screening, target-to-compounds workflows, and lead-finding before commit-to-medchem.
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97. ▌
    Tooluniverse Disease Research · mims-harvard bundle

    Generate comprehensive disease research reports covering genetics (causal genes, GWAS, OMIM), pathways (Reactome, KEGG), drugs (existing therapies, repurposing candidates), clinical trials, epidemiology (prevalence, incidence), and phenotypes (HPO). Use for full disease overviews, comprehensive disease characterization, and orphan/rare-disease profiling.
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98. ▌
    Tooluniverse Drug Repurposing · mims-harvard bundle

    Identify drug repurposing candidates via target-based, compound-based, and disease-based strategies. Combines drug-target-disease network reasoning with mechanism rationale, clinical-trial precedent, and patent/regulatory feasibility. Use for hypothesis-generating repurposing for orphan diseases, finding existing drugs for new indications, and prioritizing candidates by evidence and feasibility.
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99. ▌
    Tooluniverse Gwas Finemapping · mims-harvard bundle

    Statistical fine-mapping of GWAS loci using credible sets (SuSiE, FINEMAP) and locus-to-gene scoring (Open Targets L2G). Identifies likely causal variants and target genes — distinct from positional 'nearest gene' which is often wrong. Use for prioritizing causal variants at GWAS hits, comparing fine-mapping methods, and converting lead SNPs to target genes.
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100. ▌
     Tooluniverse Pharmacogenomics · mims-harvard

     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.
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