Functional Genomics Screen Interpretation

Pipeline for validating and prioritizing hits from genetic screens (CRISPR-KO, CRISPRi, shRNA) by integrating essentiality (DepMap), constraint (gnomAD), pathways (Reactome, STRING), druggability (DGIdb), and clinical evidence (CIViC, COSMIC).

Guiding principles:

1. Hits are hypotheses -- screen results contain false positives; validate through orthogonal evidence
2. Selectivity matters -- pan-essential genes are poor drug targets; context-specific essentiality is high-value
3. Pathway over gene -- enriched pathways are more robust than individual hits
4. Druggability is practical -- prioritize chemically modulable targets
5. English-first queries -- use English gene names in tool calls

LOOK UP, DON'T GUESS

When uncertain about any scientific fact, SEARCH databases first.

COMPUTE, DON'T DESCRIBE

When analysis requires computation (statistics, data processing, scoring, enrichment), write and run Python code via Bash. Don't describe what you would do — execute it and report actual results. Use ToolUniverse tools to retrieve data, then Python (pandas, scipy, statsmodels, matplotlib) to analyze it.