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- ▌ Tooluniverse Protein Therapeutic Design 2 · mims-harvard bundleAI-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.
- ▌ Tooluniverse Acmg Variant Classification 2 · mims-harvardSystematic 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.
- ▌ Tooluniverse Systems Biology 2 · mims-harvard bundleSystems 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.
- ▌ Tooluniverse Target Research 2 · mims-harvard bundleComprehensive 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.
- ▌ Tooluniverse Admet Prediction 2 · mims-harvardComprehensive 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.
- ▌ Tooluniverse Aging Senescence 2 · mims-harvardAging 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).
- ▌ Tooluniverse Binder Discovery 2 · mims-harvard bundleDiscover 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.
- ▌ Tooluniverse Disease Research 2 · mims-harvard bundleGenerate 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.
- ▌ Tooluniverse Drug Repurposing 2 · mims-harvard bundleIdentify 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.
- ▌ Tooluniverse Gwas Finemapping 2 · mims-harvard bundleStatistical 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.
- ▌ Tooluniverse Pharmacogenomics 2 · mims-harvardPharmacogenomics (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.
- ▌ Tooluniverse Pharmacokinetics 2 · mims-harvard bundlePharmacokinetic (PK) analysis of concentration-time data — non-compartmental analysis (NCA) for Cmax, Tmax, AUC (0-t and 0-∞), terminal half-life, clearance (CL), volume of distribution (Vd), MRT, and absolute bioavailability (F). Also one-compartment fitting. Use when you have plasma/serum drug concentrations over time after a dose and need PK parameters, or to compute bioavailability from IV + oral AUCs. NOT for ADMET property prediction from structure (use tooluniverse-admet-prediction).
- ▌ Tooluniverse Variant Analysis 2 · mims-harvard bundleVCF and variant analysis — parsing, annotation, classification (synonymous, missense, frameshift, stop_gained), VAF filtering, coding vs non-coding categorization, multi-condition variant comparison. Use for VCF parsing, variant fraction calculations (denominator = coding subset only, NOT all variants), and per-sample mutation profiling.
- ▌ Tooluniverse Primer Design 2 · mims-harvard bundlePCR / 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.
- ▌ Tooluniverse Rnaseq Deseq2 2 · mims-harvard bundleRNA-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).
- ▌ Tooluniverse Data Wrangling 2 · mims-harvard bundleUniversal 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.
- ▌ Tooluniverse Gene Liability 2 · mims-harvardEvaluate 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.
- ▌ Tooluniverse Image Analysis 2 · mims-harvard bundleMicroscopy 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.
- ▌ Tooluniverse Install Skills 2 · mims-harvardDetect 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.
- ▌ Tooluniverse Plant Genomics 2 · mims-harvardPlant 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.
- ▌ Tooluniverse Vaccine Design 2 · mims-harvard bundleComputational 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.
- ▌ Tooluniverse Chemical Safety 2 · mims-harvard bundleChemical 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.
- ▌ Tooluniverse Drug Regulatory 2 · mims-harvardDrug 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.
- ▌ Tooluniverse Enzyme Kinetics 2 · mims-harvard bundleEnzyme 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).
- ▌ Tooluniverse Gene Enrichment 2 · mims-harvard bundleGene-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.
- ▌ Tooluniverse Epigenomics 2 · mims-harvard bundleGenomics and epigenomics analysis: DNA methylation (CpG, 5mC, 5hmC, bisulfite, RRBS), m6A RNA modification (MeRIP-seq), ChIP-seq peaks, ATAC-seq accessibility, histone modifications, chromatin state, multi-omics integration. Combines pandas/scipy/pysam computation with ToolUniverse annotation tools. Use for genome-wide epigenomic statistics, methylation analysis, and chromatin-genome integration.
- ▌ Tooluniverse Self Review 2 · mims-harvard bundleReview existing work against the user's actual goal and surface evidence-backed strengths, gaps, risks, and next fixes. Use when asked to eval, evaluate, review, assess, or check current/this/my/our work; decide whether a task is complete; build a definition-of-done checklist or rubric; or perform grading, LLM-as-judge, Qworld, or RET evaluation. Treat plain eval/review requests as qualitative: resolve "current work" from the conversation, artifacts, files, or diff, and never assign numeric scores unless the user explicitly requests scores, grades, points, ratings, weighted criteria, Qworld, or RET. Do not use for implementing automated eval suites, tests, graders, or benchmarks.
- ▌ Tooluniverse Single Cell 2 · mims-harvard bundleSingle-cell RNA-seq analysis with scanpy/anndata — h5ad data loading, scRNA-seq quality control and QC gating (n_genes_by_counts, total_counts, mitochondrial percent / pct_counts_mt, pct_counts_ribo, doublet detection with Scrublet/scDblFinder, ambient RNA / SoupX awareness, empty-droplet filtering, MAD-based thresholds), normalization, dimensionality reduction (PCA, UMAP, t-SNE), clustering (Leiden, Louvain), marker gene identification, cell-type annotation, pseudotime/trajectory analysis. Use for any scRNA-seq workflow, including deciding which cells to filter, flag, or investigate before downstream analysis.
- ▌ Tooluniverse Codex Plugin 2 · mims-harvardInstall, set up, verify, update, pin, uninstall, or troubleshoot the ToolUniverse plugin on OpenAI Codex. ALWAYS consult this skill for any of those — don't answer from memory, because the exact marketplace name (mims-harvard/ToolUniverse), the "codex plugin marketplace add" then "codex plugin add -m tooluniverse" flow, Codex's startup auto-upgrade behavior, the uvx tooluniverse MCP server, and the API-key env vars are easy to get wrong. Use it whenever someone wants to get ToolUniverse (or "the 1000+ scientific tools" / "the harvard tools") working on Codex, says the Codex plugin or its tools/skills won't load, hits a uvx or MCP-server startup error, asks how Codex updates it, wants to pin or remove it, or finds it running an old tool version — even if they never say the word "plugin". Not for the Claude Code plugin (use tooluniverse-claude-code-plugin), for running research with the tools, or for authoring new tools or skills.
- ▌ Tooluniverse Drug Synergy 2 · mims-harvard bundleDrug-combination synergy analysis — quantify whether two drugs together are synergistic, additive, or antagonistic using the standard reference models (Bliss independence, HSA / highest single agent, Loewe additivity, ZIP, and the Chou-Talalay Combination Index). Use when you have measured single-drug and combination effects (inhibition/viability) and need a synergy score. Explains which model to use, what data each one needs, and how to read the score. NOT for looking up pre-computed synergy in a database (use the SYNERGxDB tool / cell-line-profiling skill).
- ▌ Tooluniverse Metabolomics 2 · mims-harvard bundleMetabolomics research — metabolite identification, study analysis, and database searches across HMDB, MetaboLights, Metabolomics Workbench, KEGG. Use for annotating mass-spec features to known metabolites, finding metabolomics studies of a disease, and structured metabolomics research reports with metabolite-pathway mapping.
- ▌ Tooluniverse Neuroscience 2 · mims-harvardNeuroscience research workflows: neuroanatomy, neural circuits, neurotransmitter biology, neurological/psychiatric disease genetics, neural-protein function. Uses Allen Brain Atlas, WormBase (C. elegans connectome), UniProt for neural proteins, PubMed for primary literature. Use for brain-region biology, neural development, neurodegeneration mechanisms (Alzheimer's, Parkinson's, ALS), and synaptic-protein characterization.
- ▌ Tooluniverse Dose Response 2 · mims-harvard bundleDose-response / concentration-response curve fitting — IC50, EC50, Hill slope, Emax/Emin efficacy, and relative potency from paired concentration vs response data (enzyme/cell assays, drug screening, agonist/antagonist pharmacology). Fits the 4-parameter logistic (Hill sigmoidal) model. Use when you have concentrations + responses and need a potency value, to compare two compounds' potency, or to judge curve quality. NOT for image-derived dose-response (use tooluniverse-image-analysis) and NOT for survival/regression (use tooluniverse-statistical-modeling).
- ▌ Tooluniverse Drug Research 2 · mims-harvard bundleComprehensive drug profiling — mechanism, primary/secondary targets, drug interactions, clinical-trial status, adverse events (FAERS), pharmacogenomics, and approval history. Use for full drug investigation reports, 'tell me about drug X' queries, and assembling drug profiles for clinicians, researchers, or regulatory work.
- ▌ Tooluniverse Meta Analysis 2 · mims-harvard bundleMeta-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).
- ▌ Tooluniverse Noncoding Rna 2 · mims-harvardNon-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.
- ▌ Devtu Create Tool · mims-harvard bundleCreate new scientific tools for ToolUniverse framework with proper structure, validation, and testing. Use when users need to add tools to ToolUniverse, implement new API integrations, create tool wrappers for scientific databases/services, expand ToolUniverse capabilities, or follow ToolUniverse contribution guidelines. Supports creating tool classes, JSON configurations, validation, error handling, and test examples.
- ▌ Devtu Code Optimization · mims-harvard bundleCode quality patterns and guidelines for ToolUniverse tool development. Apply when writing, fixing, or refactoring tool Python code in the ToolUniverse project. Encodes lessons from 80+ debug rounds. Use alongside devtu-fix-tool and devtu-self-evolve. Triggers: implementing tool fixes, writing new tool classes, reviewing tool code quality, checking schema correctness, looking up API-specific bug fixes.
- ▌ Devtu Auto Discover Apis · mims-harvard bundleAutomatically discover life science APIs online, create ToolUniverse tools, validate them, and prepare integration PRs. Performs gap analysis to identify missing tool categories, web searches for APIs, automated tool creation using devtu-create-tool patterns, validation with devtu-fix-tool, and git workflow management. Use when expanding ToolUniverse coverage, adding new API integrations, or systematically discovering scientific resources.
- ▌ Tooluniverse 2 · mims-harvard bundleToolUniverse plugin router. STEP 1 BEFORE ANY ANALYSIS: if the data folder contains `*_executed.ipynb`, run `tu run read_executed_notebook '{"data_folder":"<path>","search":"<keyword>"}'` to extract its cell outputs and apply EVERY filter/sample-exclusion the notebook used — even when the question says 'Using DESeq2/Run X/Compute Y' (this describes the METHOD the notebook used, not a request to rerun). The notebook's cell outputs are the only published authoritative answers; reimplementing or reading stale pre-computed CSVs in the data folder produces different numbers because of outlier-sample removal, library version, and filter steps you don't see by skimming. STEP 2 routing — pick a sub-skill name from this exact list (never invent): tooluniverse-rnaseq-deseq2 (RNA/miRNA-seq DE, correlation, PCA, clustering, dispersion), tooluniverse-gene-enrichment (GO/KEGG/Reactome/GSEA/pathway enrichment), tooluniverse-statistical-modeling (regression, ANOVA, ordinal/logistic, chi-square...
- ▌ Tooluniverse Phylogenetics 2 · mims-harvard bundlePhylogenetic 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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- ▌ Tooluniverse Biomedical Fact Lookup 2 · mims-harvardAnswer 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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- ▌ Optimuskg · mims-harvard bundleGuide for using OptimusKG, the biomedical knowledge graph, through the `optimuskg` Python client. Use this when loading, querying, filtering, or analyzing OptimusKG data — genes, drugs, diseases, phenotypes, anatomy, pathways, and their relationships — as Polars DataFrames or a NetworkX graph, or when downloading the published graph from Harvard Dataverse.
- ▌ Node Catalog Sync · mims-harvardEnforce synchronization between Kedro node files and catalog YAML files in the OptimusKG project. Use when editing any Python node file under optimuskg/pipelines/*/nodes/, including modifying run() functions, changing node() inputs/outputs, adding/removing/renaming DataFrame columns, or changing column types. Also use when creating new nodes or deleting existing ones.
- ▌ Multi Agent Focus · mims-harvard bundleGeneric skill for self-organizing multi-agent teams that collaborate on an optimization problem. Agents discuss dimensions, form teams, run experiments, and adapt when stagnating. Uses AnonAPI posts for discussion and workspaces for shared state.
- ▌ External Repo Setup · mims-harvard bundleProtocol for GPU agents to clone external GitHub repos, install their dependencies, download pretrained weights, and integrate them as featurizers or models inside a focus-area train.py. Use this when a proposal references a GitHub repo or pretrained checkpoint that is not already present in the focus-area workspace.
- ▌ Qworld Criteria Generation · mims-harvardGenerate question-specific evaluation criteria using the Qworld Recursive Expansion Tree (RET) algorithm. Decomposes any open-ended question into scenarios, perspectives, and fine-grained binary criteria through structured horizontal and hierarchical expansion. Use when asked to create evaluation rubrics, generate grading criteria, build scoring rubrics for LLM responses, assess answer quality for open-ended questions, or when the user mentions "criteria generation", "evaluation rubrics", "evaluation criteria", "Qworld", or "RET algorithm".
- ▌ Tooluniverse Variant To Mechanism · mims-harvardEnd-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.
- ▌ Setup Transcriptformer Remote Tool · mims-harvard bundleSet up, launch, validate, and troubleshoot the TranscriptFormer ToolUniverse remote tool and optionally relay it through ToolUniverse Connect. Use when deploying or auditing this implementation.
- ▌ Setup Uspto Downloader Remote Tool · mims-harvard bundleSet 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.
- ▌ Tooluniverse Cancer Classification · mims-harvardTranslate 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.
- ▌ Tooluniverse Clinical Risk Scoring · mims-harvard bundleCompute 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
- ▌ Tooluniverse Clinical Trial Design · mims-harvard bundleStrategic 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.
- ▌ Tooluniverse Drug Drug Interaction · mims-harvard bundleAssess 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.
- ▌ Tooluniverse Epigenomics Chromatin · mims-harvardHistone-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.
- ▌ Tooluniverse Metabolomics Analysis · mims-harvard bundleAnalyze 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.
- ▌ Tooluniverse Metagenomics Analysis · mims-harvardMicrobiome 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.
- ▌ Tooluniverse Nih Funding Landscape · mims-harvard bundleAnalyze 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.
- ▌ Tooluniverse Protein Lof Mechanism · mims-harvardPropose 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.
- ▌ Tooluniverse Rare Disease Genomics · mims-harvardRare 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.
- ▌ Tooluniverse Structural Proteomics · mims-harvardStructural 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.
- ▌ Tooluniverse Biomedical Fact Lookup · mims-harvard bundleAnswer 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.
- ▌ Tooluniverse Crispr Screen Analysis · mims-harvard bundleAnalyze 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.
- ▌ Tooluniverse Drug Target Validation · mims-harvard bundleQuantitative 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.
- ▌ Tooluniverse Rare Disease Diagnosis · mims-harvard bundleRare 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.
- ▌ Tooluniverse Spatial Omics Analysis · mims-harvard bundleSpatial 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.
- ▌ Tooluniverse Variant Interpretation · mims-harvard bundleClinical 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".
- ▌ Tooluniverse Adverse Event Detection · mims-harvard bundleDetect 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.
- ▌ Tooluniverse Adverse Outcome Pathway · mims-harvardMap 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).
- ▌ Tooluniverse Clinical Trial Matching · mims-harvard bundleAI-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.
- ▌ Tooluniverse Drug Mechanism Research · mims-harvardTrace 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.
- ▌ Tooluniverse Gwas Snp Interpretation · mims-harvard bundleInterpret 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.
- ▌ Tooluniverse Mendelian Randomization · mims-harvard bundleMendelian 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
- ▌ Tooluniverse Model Organism Genetics · mims-harvardCross-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.
- ▌ Tooluniverse Multi Omics Integration · mims-harvard bundleMulti-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.
- ▌ Tooluniverse Spatial Transcriptomics · mims-harvard bundleSpatial 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.
- ▌ Tooluniverse Molecular Cloning · mims-harvard bundleMolecular 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.
- ▌ Tooluniverse Computational Biophysics · mims-harvard bundleSolve 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.
- ▌ Tooluniverse Epidemiological Analysis · mims-harvardEnd-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.
- ▌ Tooluniverse Gene Disease Association · mims-harvardGene-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.
- ▌ Tooluniverse Gene Regulatory Networks · mims-harvardGene 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.
- ▌ Tooluniverse Literature Deep Research · mims-harvard bundleDeep 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.
- ▌ Tooluniverse Pathway Disease Genetics · mims-harvardConnect 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.
- ▌ Tooluniverse Small Molecule Discovery · mims-harvardSmall 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.
- ▌ Tooluniverse Clinical Data Integration · mims-harvardEnd-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.
- ▌ Tooluniverse Data Integration Analysis · mims-harvardIntegrate 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.
- ▌ Tooluniverse Expression Data Retrieval · mims-harvard bundleRetrieve 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.
- ▌ Tooluniverse Proteomics Data Retrieval · mims-harvardFind 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.
- ▌ Tooluniverse Diagnostic Test Evaluation · mims-harvard bundleDiagnostic 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.
- ▌ Tooluniverse Immune Repertoire Analysis · mims-harvard bundleTCR/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.
- ▌ Tooluniverse Protein Therapeutic Design · mims-harvard bundleAI-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.
- ▌ Tooluniverse Phewas · mims-harvardCross-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).
- ▌ Tooluniverse Acmg Variant Classification · mims-harvardSystematic 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.
- ▌ Tooluniverse Chemical Compound Retrieval · mims-harvard bundleRetrieve 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).
- ▌ Tooluniverse Functional Genomics Screens · mims-harvardInterpret 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.
- ▌ Tooluniverse Product Safety Surveillance · mims-harvard bundlePost-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
- ▌ Tooluniverse Protein Structure Retrieval · mims-harvard bundleProtein 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.