tooluniverse-crispr-screen-analysis

Analyze CRISPR-Cas9 screens with MAGeCK scoring, QC, enrichment, and drug target prioritization.

1.7k|254|Updated Mar 3, 2025
One-click install
npx skills add https://github.com/mims-harvard/ToolUniverse --skill tooluniverse-crispr-screen-analysis
Or copy as Structured Prompt for Agent
Please help me install this Agent Skill.
Skill: tooluniverse-crispr-screen-analysis
Source: https://github.com/mims-harvard/ToolUniverse/tree/main/plugins/tooluniverse/skills/tooluniverse-crispr-screen-analysis
Command: npx skills add https://github.com/mims-harvard/ToolUniverse --skill tooluniverse-crispr-screen-analysis

SYSTEM DOCUMENTATION & REQUIREMENTS

💡 This Skill requires pandas, numpy, scipy, tooluniverse, and includes scripts (resource) components.

What problem does it solve?

Interpreting CRISPR-Cas9 genetic screens requires chaining together sgRNA count processing, quality control, gene-level essentiality scoring, pathway enrichment, and druggability assessment — a workflow that is error-prone and slow when done manually. This Skill provides a complete 8-phase analysis pipeline that turns raw sgRNA count matrices or gene hit lists into prioritized, clinically contextualized therapeutic target reports.

Core Features & Use Cases

  • End-to-end screen analysis: Load sgRNA count matrices, run QC (library size, Gini coefficient, low-count filtering), normalize counts, compute log2 fold changes, and score genes with MAGeCK-like RRA or BAGEL-like Bayes Factor methods using bundled CEGv2/NEGv1 reference gene sets.
  • Synthetic lethality and target discovery: Compare essentiality between wildtype and mutant contexts, then prioritize hits by integrating essentiality, expression, and DGIdb druggability into a composite priority score.
  • ToolUniverse integration: Enrich hits via Enrichr/Reactome, build STRING PPI networks, query PubMed, Pharos, and clinical trials, with a documented Pharos/Open Targets fallback when DepMap APIs are unavailable.
  • Use Case: Given 20 hits from an A549 lung cancer dropout screen, the skill classifies essentiality, finds cell-cycle checkpoint enrichment, and ranks KRAS, EGFR, and WEE1 as top targets with validation recommendations.

Quick Start

Ask the AI to analyze your CRISPR screen gene list, for example: "Analyze these CRISPR dropout screen hits from A549 lung cancer cells and generate a target prioritization report."

Frequently Asked Questions about tooluniverse-crispr-screen-analysis

High-intent search queries and answers about installing and using this skill.

FAQPage Schema
How do I analyze a CRISPR screen gene list with ToolUniverse?

Provide your gene list or cancer type in natural language, and the skill validates genes, classifies essentiality, runs pathway enrichment via Enrichr, builds STRING PPI networks, and assesses druggability via Pharos and DGIdb. It outputs a markdown report with prioritized targets and validation recommendations.

What is the difference between MAGeCK RRA and BAGEL Bayes Factor scoring?

MAGeCK-like RRA ranks all sgRNAs by log fold change and averages ranks per gene, while BAGEL-like scoring computes a Bayes Factor by comparing gene LFC distributions against reference essential (CEGv2) and non-essential (NEGv1) gene sets bundled in the scripts directory.

What happens when the DepMap API is unavailable?

The skill falls back to Open Targets and Pharos for gene validation and druggability, using TDL classification (Tclin, Tchem, Tbio, Tdark) as an essentiality proxy. Findings are labeled with reduced confidence (★★☆) since quantitative CRISPR dependency scores are unavailable.

How do I detect synthetic lethal interactions from CRISPR screens?

Process wildtype and mutant screens separately through normalization and gene scoring, then the detect_synthetic_lethality function identifies genes essential in mutant (LFC < -1.0) but not wildtype with large rank differences. Confirm candidates with delta-LFC > 1.5 in an independent cell line.

Why are ribosomal genes like RPS6 flagged as poor drug targets despite high essentiality?

Pan-cancer essential genes such as ribosomal proteins score high in every screen but offer no therapeutic window. The skill's multi-dimensional scoring penalizes pan-essential genes by cross-referencing DepMap data and prioritizing context-selective dependencies instead.

What input format does the CRISPR screen analysis expect?

The pipeline accepts a MAGeCK-format or generic TSV count matrix with sgRNA and Gene columns plus one column per sample. Alternatively, you can skip raw counts and provide a gene hit list directly for enrichment, druggability, and prioritization analysis.