drug-discovery-prompts/upstream/mims-harvard-ToolUniverse/skills/tooluniverse-cancer-variant-interpretation/QUICK_START.md

title, task, lineage_type, upstream_source, upstream_sha, imported_at, prompt_class, upstream_changes, author, validated

title	task	lineage_type	upstream_source	upstream_sha	imported_at	prompt_class	upstream_changes	author	validated
Cancer Variant Interpretation - Quick Start Guide		import	https://github.com/mims-harvard/ToolUniverse/blob/e2520a96/skills/tooluniverse-cancer-variant-interpretation/QUICK_START.md	e2520a96	2026-06-26	prompt	accepted	upstream	false

Cancer Variant Interpretation - Quick Start Guide

What This Skill Does

Given a cancer gene + variant (e.g., "EGFR L858R"), this skill produces a comprehensive clinical interpretation report covering:

• Clinical evidence and significance
• FDA-approved therapies
• Mutation prevalence
• Resistance mechanisms
• Clinical trials
• Prognostic implications

Basic Usage

Simple Variant Query

Interpret EGFR L858R for lung adenocarcinoma

Resistance Investigation

Patient progressed on osimertinib. EGFR T790M detected. What are the options?

Trial Matching

Find clinical trials for KRAS G12C mutation in any cancer type

Tumor Board Preparation

Prepare molecular tumor board report: BRAF V600E in colorectal cancer

Step-by-Step Workflow

Step 1: Gene Resolution

Resolve the gene to all required IDs:

# MyGene: Get Ensembl + Entrez IDs
gene_info = tu.tools.MyGene_query_genes(query='EGFR', species='human')
# -> hits[0]: symbol='EGFR', ensembl.gene='ENSG00000146648', entrezgene='1956'

# UniProt: Get protein accession
uniprot = tu.tools.UniProt_search(query='gene:EGFR', organism='human', limit=3)
# -> results[0].accession = 'P00533'

# OpenTargets: Get ensemblId + description
ot = tu.tools.OpenTargets_get_target_id_description_by_name(targetName='EGFR')
# -> data.search.hits[0].id = 'ENSG00000146648'

Step 2: Clinical Evidence (CIViC)

# Get gene from CIViC (paginate to find)
genes = tu.tools.civic_search_genes(limit=100)
# Find gene by name in results

# Get all variants for the gene
variants = tu.tools.civic_get_variants_by_gene(gene_id=CIVIC_GENE_ID, limit=200)
# Find matching variant by name (e.g., 'V600E')

Step 3: Mutation Prevalence (cBioPortal)

# Get mutations in a TCGA study
mutations = tu.tools.cBioPortal_get_mutations(study_id='luad_tcga', gene_list='EGFR')
# Returns: [{proteinChange: 'L858R', mutationType: 'Missense_Mutation', sampleId: '...'}]

Step 4: Therapeutic Options

# OpenTargets: All drugs targeting the gene
drugs = tu.tools.OpenTargets_get_associated_drugs_by_target_ensemblID(
    ensemblId='ENSG00000146648', size=50
)
# Returns: approved drugs, phase info, mechanism of action

# FDA label
fda = tu.tools.FDA_get_indications_by_drug_name(drug_name='osimertinib', limit=3)
# Returns: approved indications, dosing

# DrugBank details
db = tu.tools.drugbank_get_drug_basic_info_by_drug_name_or_id(
    query='osimertinib', case_sensitive=False, exact_match=False, limit=3
)
# Returns: drug description, mechanism

Step 5: Clinical Trials

trials = tu.tools.search_clinical_trials(
    query_term='EGFR L858R',
    condition='non-small cell lung cancer',
    pageSize=20
)
# Returns: {studies: [{NCT ID, brief_title, overall_status, phase}]}

Step 6: Resistance & Literature

# Resistance literature
resistance = tu.tools.PubMed_search_articles(
    query='"EGFR" AND "osimertinib" AND resistance',
    limit=10, include_abstract=True
)

# Pathway context
pathways = tu.tools.Reactome_map_uniprot_to_pathways(id='P00533')

Common Pitfalls

Issue	Solution
OpenTargets param error	Use ensemblId (camelCase), NOT ensemblID
CIViC gene not found	Gene search returns alphabetically, limited to 100 per page
DrugBank error	All 4 params required: query, case_sensitive, exact_match, limit
MyGene param error	Use query, NOT q
Clinical trials empty	Use broader query_term (e.g., "EGFR mutation" instead of "EGFR L858R")
ChEMBL mechanisms error	Use drug_chembl_id__exact, NOT chembl_id
GTEx empty results	Use versioned Ensembl ID (e.g., ENSG00000146648.12)
OpenTargets drug lookup	Use drugName parameter, NOT genericName

cBioPortal Study IDs (Quick Reference)

Cancer Type	Study ID
Lung Adenocarcinoma	luad_tcga
Breast Cancer	brca_tcga
Colorectal	coadread_tcga
Melanoma	skcm_tcga
Pancreatic	paad_tcga
Glioblastoma	gbm_tcga
Prostate	prad_tcga

Output Format

The skill generates a markdown report file named {GENE}_{VARIANT}_cancer_variant_report.md with sections:

1. Executive Summary (1-2 sentences + actionability score)
2. Gene & Variant Overview
3. Clinical Variant Evidence
4. Mutation Prevalence
5. Therapeutic Options (prioritized by evidence tier)
6. Resistance Mechanisms
7. Clinical Trials
8. Prognostic Impact
9. Evidence Grading Summary
10. Data Sources
11. Completeness Checklist