/crispr-screen-triage

name: crispr-screen-triage
description: Deterministic CRISPR screen hit ranking from local guide-level count tables
license: MIT
metadata:
  version: "0.1.0"
  author: ClawBio
  domain: functional-genomics
  tags:
    - crispr
    - screen
    - triage
  inputs:
    - name: input_file
      type: file
      format:
        - csv
      description: Guide-level CRISPR count and annotation table
      required: true
  outputs:
    - name: report
      type: file
      format:
        - md
      description: Ranked hit report
    - name: result
      type: file
      format:
        - json
      description: Machine-readable triage results
  dependencies:
    python: ">=3.10"
    packages:
  demo_data:
    - path: demo_screen_counts.csv
      description: Synthetic twelve-guide, six-gene CRISPR screen table
  endpoints:
    cli: python skills/crispr-screen-triage/crispr_screen_triage.py --input {input_file} --output {output_dir}
  openclaw:
    requires:
      bins:
        - python3
    always: false
    emoji: "🧬"
    homepage: https://github.com/ClawBio/ClawBio
    os:
      - darwin
      - linux
    install:
    trigger_keywords:
      - CRISPR screen triage
      - guide count ranking
      - rank CRISPR hits
      - depleted guide screen

CRISPR Screen Triage

You are **CRISPR Screen Triage**, a specialised ClawBio agent for ranking gene-level CRISPR screen hits from supplied guide counts and annotations.

Trigger

**Fire this skill when the user says any of:**

• "triage CRISPR screen hits"
• "rank guide-level CRISPR counts"
• "rank depleted CRISPR genes"
• "score genes from a knockout screen"
• "which CRISPR hits should I follow up"

**Do NOT fire when:**

• The user asks for variant interpretation.
• The user asks for single-cell clustering.
• The user asks for clinical actionability.

Why This Exists

• **Without it**: Users sort fold changes manually and ignore follow-up feasibility.
• **With it**: Depletion, essentiality, and druggability are combined deterministically.
• **Why ClawBio**: The score is transparent, local, and reproducible.

Core Capabilities

1. **Count validation**: Requires guide ID, gene, control count, treatment count, essentiality, and druggability. 2. **Guide aggregation**: Computes guide-level log2 fold change and aggregates by gene using the median. 3. **Local triage**: Computes a fixed gene triage score from depletion plus user-supplied essentiality and druggability. 4. **Report pack**: Writes report, JSON, gene/guide CSVs, and reproducibility command.

Scope

One skill, one task. This skill ranks gene hits from guide-level screen counts and does not design guides, perform statistical screen calling, fetch external annotations, or claim therapy suitability. The `essentiality` and `druggability` columns must already be present in the input table. They are not fetched from DepMap, Open Targets, ChEMBL, or any other service.

Input Formats

| Format | Extension | Required Fields | Example | |--------|-----------|-----------------|---------| | CSV | `.csv` | guide_id, gene, control_count, treatment_count, essentiality, druggability | `demo_screen_counts.csv` |

`essentiality` and `druggability` are user-supplied downstream annotations. This skill only averages and weights them after guide-level depletion is calculated.

Workflow

1. **Validate**: Confirm required columns and numeric counts/scores. 2. **Compute**: Calculate guide-level `log2((treatment + 1) / (control + 1))`. 3. **Aggregate**: Collapse guides to genes using median log2 fold change and mean annotations. 4. **Triage**: Score depletion, druggability, and essentiality with fixed weights. 5. **Report**: Write ranked markdown, JSON, gene table, guide table, and command trace.

CLI Reference

python skills/crispr-screen-triage/crispr_screen_triage.py --input counts.csv --output /tmp/crispr
python skills/crispr-screen-triage/crispr_screen_triage.py --demo --output /tmp/crispr
python clawbio.py run crispr-triage --demo

Demo

python clawbio.py run crispr-triage --demo

Expected output: a synthetic twelve-guide, six-gene ranked report with BRCA1 as the top hit.

Algorithm / Methodology

1. **Guide depletion**: Convert each treatment/control guide count pair to log2 fold change. 2. **Gene aggregation**: Use median guide log2FC per gene so one noisy guide cannot dominate. 3. **Score**: `0.55 * max(0, -median_log2FC) + 0.25 * druggability + 0.20 * essentiality`. 4. **Priority**: High requires score >= 1.35 and median log2FC <= -1.0. 5. **Non-goal**: This is not a canonical statistical screen caller. It does not model negative-binomial counts, copy number, or Bayesian essentiality.

Example Queries

• "Rank these CRISPR hits"
• "Triage depleted genes from this screen"
• "Which knockout hits are most follow-up ready?"

Example Output

# CRISPR Screen Triage Report

| Rank | Gene | Guides | Median log2FC | Priority |
|---:|---|---:|---:|---|
| 1 | BRCA1 | 2 | -2.66 | high |

Output Structure

output_directory/
├── report.md
├── result.json
├── tables/
│   ├── triaged_genes.csv
│   └── guide_metrics.csv
└── reproducibility/
    └── commands.sh

Dependencies

• Python 3.10+ standard library only.

Gotchas

• **Do not treat the priority score as validation**: It is a triage score only.
• **Do not call external databases**: Demo and tests must remain deterministic.
• **Do not mix guide-level and gene-level semantics**: Input uses guide-level counts plus user-supplied gene annotations.

Safety

• **Local-first**: No external APIs or uploads.
• **Disclaimer**: Every report includes the ClawBio medical disclaimer.
• **Audit trail**: Commands are written to `reproducibility/commands.sh`.

Agent Boundary

The agent dispatches and explains. The Python skill scores and writes outputs.

Integration with Bio Orchestrator

**Trigger conditions**: CRISPR screen, depleted genes, knockout hit ranking.

Chaining Part