ToolUniverse

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.

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.

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.

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.

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.

Drug and chemical toxicity assessment via adverse outcome pathways (AOPs), real-world FAERS adverse event signals, FDA labels, and toxicogenomic associations. Triangulates molecular initiating event to cellular outcome to organ-level toxicity to clinical adverse event. Use for hepatotoxicity/cardiotoxicity/nephrotoxicity prediction and toxicology reports.

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.

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.

VCF 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.

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.

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.

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".

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".

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.

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.

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.