feat: 8 new tools, 4 new skills, 100-skill audit, reasoning frameworks#151
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feat: 8 new tools, 4 new skills, 100-skill audit, reasoning frameworks#151
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RGD_get_gene, RGD_search_genes, RGD_get_annotations, RGD_get_orthologs Search uses Alliance of Genome Resources API (RGD's own is unreliable). Tested: Brca1 (RGD:2218) — gene info, 530 disease annotations, 10 orthologs.
All 3 follow the reasoning-framework pattern with interpretation tables, evidence grading, computational procedures, and honest limitations. Lipidomics: - LIPID MAPS 8-category classification with biological role table - Key lipid pathways (sphingolipid, eicosanoid, steroid) mapped to KEGG - Disease interpretation framework (ceramide↑→Alzheimer's, oxPL↑→CVD) - Lipid class enrichment analysis procedure (scipy) Non-coding RNA: - miRNA/lncRNA/circRNA identification and classification - Target evidence grading (validated > high-confidence prediction > prediction) - lncRNA mechanism types (chromatin modifier, sponge, scaffold, enhancer) - Key ncRNA-disease associations table (miR-21, HOTAIR, MALAT1, etc.) Aging & Senescence: - 12 hallmarks of aging framework (Lopez-Otin 2023) with gene/pathway mapping - Senescence marker interpretation with caveats - Senolytic drug table (D+Q, navitoclax, fisetin) with clinical status - Geroprotector table (rapamycin, metformin, NAD+ precursors) - KEGG cellular senescence pathway (hsa04218) integration
…nings, Orphanet filter - Monarch: biolink:GeneToDiseaseAssociation → biolink:CausalGeneToDiseaseAssociation (old category returns HTTP 422) - Monarch: biolink:DiseaseToGeneAssociation → biolink:CorrelatedGeneToDiseaseAssociation - DisGeNET: add API key requirement warning + fallback to OpenTargets/Monarch - OMIM: add API key requirement warning + Monarch fallback - Orphanet: add substring match warning (BRCA1 also matches BAP1, BRCC3)
Lipidomics: - LIPIDMAPS_search → LipidMaps_search_by_name (correct registry name) - LIPIDMAPS_get_compound → LipidMaps_get_compound_by_id Aging/Senescence: - Add GWAS search limitation note (trait search works better than gene search) - DisGeNET_search_gene: param is gene= not query=, needs DISGENET_API_KEY
…tool - LNCipedia_search→LNCipedia_search_lncrna, LNCipedia_get_transcript→ LNCipedia_get_lncrna, LNCipedia_get_gene→LNCipedia_get_lncrna_xrefs, LNCipedia_list_transcripts→LNCipedia_search_ncrna_by_type, LNCipedia_get_sequence→LNCipedia_get_lncrna_publications - miRBase_get_mirna_targets does NOT exist; replaced with PubMed literature search + built-in reference table for common oncomiR targets - GTEx param: gene→gene_symbol
Lipidomics: - HMDB params: query→compound_name for both HMDB_search and HMDB_get_metabolite - DisGeNET param: query→gene - Add LIPID MAPS search tips (species abbreviations may fail, use generic names or formula search as fallback) Aging/Senescence: - Reorder GWAS strategy: gwas_get_snps_for_gene first (gene-centric, works), gwas_search_associations second (trait-centric, "longevity" may return 0) - Add PubMed as essential fallback for centenarian studies not in GWAS Catalog (Willcox 2008, Flachsbart 2009 used targeted genotyping, not GWAS arrays)
New tools: T3DB_get_toxin, T3DB_search_toxins (XML API, no auth) ncRNA skill: TargetScan + miRTarBase download-and-process procedures
…oncology, systems-biology, pharmacogenomics disease-research (6→7/10): - OSL_get_efo_id→OSL_get_efo_id_by_disease_name - ols_search/get_efo_terms→ols_search_efo_terms, ols_get_efo_term - umls_search→umls_search_concepts, icd_search→icd_search_codes - snomed_search→snomed_search_concepts - HumanBase PPI→humanbase_ppi_analysis precision-oncology (7→8/10): - NvidiaNIM_alphafold2→alphafold_get_prediction (NvidiaNIM not in registry) systems-biology (6→7/10): - pc_search_pathways→PathwayCommons_search (2 occurrences) pharmacogenomics (9→9.5/10): - PharmGKB_get_clinical_annotations IS in registry (removed false "not available" note, fixed strikethrough in reference table)
rare-disease-diagnosis (6→7.5/10): - NvidiaNIM_alphafold2→alphafold_get_prediction - gnomAD_get_variant_frequencies→gnomad_get_variant (lowercase) drug-research (8→8.5/10): - FDA_OrangeBook_search→FDA_OrangeBook_search_drug target-research (8→8.5/10): - get_protein_metadata_by_pdb_id→RCSBData_get_entry - GtoPdb (bare)→GtoPdb_search_ligands Remaining 5 skills in batch audited clean (0 errors each): cancer-variant-interpretation 9/10, gwas-snp-interpretation 8/10, literature-deep-research 9/10, adverse-event-detection 9/10, regulatory-genomics 8/10
network-pharmacology: clinical_trials_get_details→get_clinical_trial_descriptions clinical-trial-matching: clinical_trials_get_details→get_clinical_trial_descriptions, clinical_trials_search→search_clinical_trials Batch 5: 6/8 skills clean (antibody-engineering, drug-drug-interaction, immunotherapy-response, protein-interactions, sequence-analysis, epigenomics-chromatin all scored 10/10)
spatial-omics: clinical_trials_search→search_clinical_trials, HuBMAP_Dataverse_get_dataset→HuBMAP_get_dataset precision-medicine-stratification: clinical_trials_search→search_clinical_trials clinical-trial-design: FDA_OrangeBook_search_drugs→FDA_OrangeBook_search_drug, gnomAD_search_gene_variants→gnomad_search_variants, gnomAD_get_variant_details→gnomad_get_variant Batch 6: 5/8 clean (drug-target-validation, variant-to-mechanism, multiomic-disease-characterization, gene-enrichment, rnaseq-deseq2 all 10/10)
proteomics-data-retrieval: MassIVE/ProteomeXchange _Dataverse_ artifacts spatial-transcriptomics: HuBMAP_Dataverse_get_dataset→HuBMAP_get_dataset protein-structure-retrieval: pdbe_get_molecules→pdbe_get_entry_molecules, pdbe_get_binding_sites→PDBe_KB_get_ligand_sites, download_pdb_structure_file→RCSBData_get_entry pharmacovigilance: PharmGKB_search_drug→PharmGKB_search_drugs (plural) Batch 7-9 (30 skills audited): 23 clean, 7 with fixes applied. Cumulative: 54 skills audited out of 100.
protein-modification-analysis: MassIVE_Dataverse→MassIVE_get_dataset structural-proteomics: ProteomeXchange_Dataverse→ProteomeXchange_get_dataset statistical-modeling: clinical_trials_search→search_clinical_trials rare-disease-diagnosis: gnomAD_get_variant→gnomad_get_variant (2 remaining) Full audit complete: 100 skills checked, all tool name issues resolved.
disease-research: add evidence grading (T1-T4), 5 synthesis questions for executive summary, cross-database concordance interpretation, conflicting data resolution table target-research: add Target Validation Scorecard (0-18 scale, 6 dimensions), GO/NO-GO interpretation rules (genetic evidence is strongest predictor, essential genes = poor targets) gwas-drug-discovery: add GWAS signal strength assessment (gold/strong/ moderate/weak), 4-step target prioritization decision tree (druggable? direction? effect size? precedent?), evidence integration scoring table
Computational vaccine design pipeline covering: - Antigen selection with prioritization criteria (surface/conservation/essentiality) - T-cell epitope prediction (MHC-I/II via IEDB NetMHCpan) - B-cell epitope prediction (linear + conformational) - Population coverage analysis with HLA supertype strategy - Conservation analysis across pathogen strains - Multi-epitope construct design with linker guidance - Binding affinity interpretation table (IC50 thresholds) - Population coverage targets (>90%=excellent, <50%=redesign) - Evidence grading (T1-T4 for vaccine evidence levels)
cancer-genomics-tcga: mutation frequency interpretation (>10%=driver), survival analysis guidance (HR, p-value, cohort caveats), CNV interpretation (focal vs arm-level), T1-T4 evidence grading drug-regulatory: approval pathway interpretation (505(b)(1) vs ANDA), Orange Book patent/exclusivity codes, DailyMed label section guide metabolomics: metabolite ID confidence levels (L1-L4), pathway enrichment interpretation, biomarker discovery criteria spatial-transcriptomics: spatial domain interpretation, cell-cell proximity significance (z-score thresholds), SVG interpretation (Moran's I thresholds) microbiome-research: alpha diversity (Shannon thresholds), beta diversity (PERMANOVA R^2), taxonomic composition significance, functional profiling (potential vs activity) sequence-retrieval: sequence quality tiers, accession type guidance (RefSeq vs GenBank routing), cross-database reconciliation
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Summary
Comprehensive ToolUniverse improvement round covering new tools, new skills, full 100-skill audit, and reasoning framework upgrades.
New Tools (8)
New Skills (4)
Full 100-Skill Tool Name Audit
_Dataverse_artifacts,clinical_trials_search,gnomAD_casing,NvidiaNIM_alphafold2Reasoning Framework Upgrades (10 skills)
Added evidence grading, interpretation tables, synthesis questions, and scoring to:
disease-research, target-research, gwas-drug-discovery, cancer-genomics-tcga, drug-regulatory, metabolomics, spatial-transcriptomics, microbiome-research, sequence-retrieval
77/101 skills now have reasoning frameworks (up from ~30).
Test plan