mims-harvard / tooluniverse-precision-oncology

Skill Content

---
name: tooluniverse-precision-oncology
description: Provide actionable treatment recommendations for cancer patients based on molecular profile. Interprets tumor mutations, identifies FDA-approved therapies, finds resistance mechanisms, matches clinical trials. Use when oncologist asks about treatment options for specific mutations (EGFR, KRAS, BRAF, etc.), therapy resistance, or clinical trial eligibility.
---

# Precision Oncology Treatment Advisor

Provide actionable treatment recommendations for cancer patients based on their molecular profile using CIViC, ClinVar, OpenTargets, ClinicalTrials.gov, and structure-based analysis.

**KEY PRINCIPLES**:
1. **Report-first** - Create report file FIRST, update progressively
2. **Evidence-graded** - Every recommendation has evidence level
3. **Actionable output** - Prioritized treatment options, not data dumps
4. **Clinical focus** - Answer "what should we do?" not "what exists?"
5. **English-first queries** - Always use English terms in tool calls (mutations, drug names, cancer types), even if the user writes in another language. Only try original-language terms as a fallback. Respond in the user's language

---

## When to Use

- "Patient has [cancer] with [mutation] - what treatments?"
- "What are options for EGFR-mutant lung cancer?"
- "Patient failed [drug], what's next?"
- "Clinical trials for KRAS G12C?"
- "Why isn't [drug] working anymore?"

---

## Phase 0: Tool Verification

| Tool | WRONG | CORRECT |
|------|-------|---------|
| `civic_get_variant` | `variant_name` | `id` (numeric) |
| `civic_get_evidence_item` | `variant_id` | `id` |
| `OpenTargets_*` | `ensemblID` | `ensemblId` (camelCase) |
| `search_clinical_trials` | `disease` | `condition` |

---

## Workflow Overview

```
Input: Cancer type + Molecular profile (mutations, fusions, amplifications)

Phase 1: Profile Validation -> Resolve gene IDs (Ensembl, UniProt, ChEMBL)
Phase 2: Variant Interpretation -> CIViC, ClinVar, COSMIC, GDC/TCGA, DepMap, OncoKB, cBioPortal, HPA
Phase 2.5: Tumor Expression -> CELLxGENE cell-type expression, ChIPAtlas regulatory context
Phase 3: Treatment Options -> OpenTargets + DailyMed (approved), ChEMBL (off-label)
Phase 3.5: Pathway & Network -> KEGG/Reactome pathways, IntAct interactions
Phase 4: Resistance Analysis -> CIViC + PubMed + NvidiaNIM structure analysis
Phase 5: Clinical Trials -> ClinicalTrials.gov search + eligibility
Phase 5.5: Literature -> PubMed, BioRxiv/MedRxiv preprints, OpenAlex citations
Phase 6: Report Synthesis -> Executive summary + prioritized recommendations
```

---

## Key Tools by Phase

### Phase 1: Profile Validation
- `MyGene_query_genes` - Resolve gene to Ensembl ID
- `UniProt_search` - Get UniProt accession
- `ChEMBL_search_targets` - Get ChEMBL target ID

### Phase 2: Variant Interpretation
- `civic_search_variants` / `civic_get_variant` - CIViC evidence
- `COSMIC_get_mutations_by_gene` / `COSMIC_search_mutations` - Somatic mutations
- `GDC_get_mutation_frequency` / `GDC_get_ssm_by_gene` - TCGA patient data
- `GDC_get_gene_expression` / `GDC_get_cnv_data` - Expression and CNV
- `DepMap_get_gene_dependencies` / `DepMap_get_drug_response` - Target essentiality
- `OncoKB_annotate_variant` / `OncoKB_get_gene_info` - Actionability
- `cBioPortal_get_mutations` / `cBioPortal_get_cancer_studies` - Cross-study data
- `HPA_search_genes_by_query` / `HPA_get_comparative_expression_by_gene_and_cellline` - Expression

### Phase 2.5: Tumor Expression
- `CELLxGENE_get_expression_data` / `CELLxGENE_get_cell_metadata` - Cell-type expression

### Phase 3: Treatment Options
- `OpenTargets_get_associated_drugs_by_target_ensemblId` - Approved drugs
- `DailyMed_search_spls` - FDA label details
- `ChEMBL_get_drug_mechanisms_of_action_by_chemblId` - Drug mechanism

### Phase 3.5: Pathway & Network
- `kegg_find_genes` / `kegg_get_gene_info` - KEGG pathways
- `reactome_disease_target_score` - Reactome disease relevance
- `intact_get_interaction_network` - Protein interactions

### Phase 4: Resistance Analysis
- `civic_search_evidence_items` - Resistance evidence (clinical_significance="Resistance")
- `PubMed_search_articles` - Resistance literature
- `NvidiaNIM_alphafold2` / `NvidiaNIM_diffdock` - Structure-based analysis

### Phase 5: Clinical Trials
- `search_clinical_trials` - Find trials (param: `condition`, NOT `disease`)
- `get_clinical_trial_eligibility_criteria` - Eligibility details

### Phase 5.5: Literature
- `PubMed_search_articles` - Published evidence
- `BioRxiv_search_preprints` / `MedRxiv_search_preprints` - Preprints (flag as NOT peer-reviewed)
- `openalex_search_works` - Citation analysis

---

## References

- [TOOLS_REFERENCE.md](TOOLS_REFERENCE.md) - Complete tool documentation with parameters and examples
- [API_USAGE_PATTERNS.md](API_USAGE_PATTERNS.md) - Detailed code examples for each phase
- [TREATMENT_ALGORITHMS.md](TREATMENT_ALGORITHMS.md) - Evidence grading, treatment prioritization, cancer type mappings, DepMap interpretation
- [REPORT_TEMPLATE.md](REPORT_TEMPLATE.md) - Report template with output tables
- [EXAMPLES.md](EXAMPLES.md) - Worked examples (EGFR NSCLC, T790M resistance, KRAS G12C, no actionable mutations)
- [CHECKLIST.md](CHECKLIST.md) - Quality and completeness checklist