leonchaox/qinyan-academic-skills/depmap

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Query the Cancer Dependency Map (DepMap) for cancer cell line gene dependency scores (CRISPR Chronos), drug sensitivity data, and gene effect profiles. Use for identifying cancer-specific vulnerabilities, synthetic lethal interactions, and validating oncology drug targets.

Install

npx vskill@latest install leonchaox/qinyan-academic-skills/depmap

SKILL.md

DepMap — Cancer Dependency Map

Overview

The Cancer Dependency Map (DepMap) project, run by the Broad Institute, systematically characterizes genetic dependencies across hundreds of cancer cell lines using genome-wide CRISPR knockout screens (DepMap CRISPR), RNA interference (RNAi), and compound sensitivity assays (PRISM). DepMap data is essential for:

  • Identifying which genes are essential for specific cancer types
  • Finding cancer-selective dependencies (therapeutic targets)
  • Validating oncology drug targets
  • Discovering synthetic lethal interactions

Key resources:

  • DepMap Portal: https://depmap.org/portal/
  • DepMap data downloads: https://depmap.org/portal/download/all/
  • Python package: depmap (or access via API/downloads)
  • API: https://depmap.org/portal/api/

When to Use This Skill

Use DepMap when:

  • Target validation: Is a gene essential for survival in cancer cell lines with a specific mutation (e.g., KRAS-mutant)?
  • Biomarker discovery: What genomic features predict sensitivity to knockout of a gene?
  • Synthetic lethality: Find genes that are selectively essential when another gene is mutated/deleted
  • Drug sensitivity: What cell line features predict response to a compound?
  • Pan-cancer essentiality: Is a gene broadly essential across all cancer types (bad target) or selectively essential?
  • Correlation analysis: Which pairs of genes have correlated dependency profiles (co-essentiality)?

Core Concepts

Dependency Scores
ScoreRangeMeaning
Chronos (CRISPR)~ -3 to 0+More negative = more essential. Common essential threshold: −1. Pan-essential genes ~−1 to −2
RNAi DEMETER2~ -3 to 0+Similar scale to Chronos
Gene EffectnormalizedNormalized Chronos; −1 = median effect of common essential genes

Key thresholds:

  • Chronos ≤ −0.5: likely dependent
  • Chronos ≤ −1: strongly dependent (common essential range)
Cell Line Annotations

Each cell line has:

  • DepMap_ID: unique identifier (e.g., ACH-000001)
  • cell_line_name: human-readable name
  • primary_disease: cancer type
  • lineage: broad tissue lineage
  • lineage_subtype: specific subtype

Core Capabilities

1. DepMap API
python
import requests
import pandas as pd
BASE_URL = "https://depmap.org/portal/api"
def depmap_get(endpoint, params=None):
url = f"{BASE_URL}/{endpoint}"
response = requests.get(url, params=params)
response.raise_for_status()
return response.json()
2. Gene Dependency Scores
python
def get_gene_dependency(gene_symbol, dataset="Chronos_Combined"):
"""Get CRISPR dependency scores for a gene across all cell lines."""
url = f"{BASE_URL}/gene"
params = {
"gene_id": gene_symbol,
"dataset": dataset
}
response = requests.get(url, params=params)
return response.json()
# Alternatively, use the /data endpoint:
def get_dependencies_slice(gene_symbol, dataset_name="CRISPRGeneEffect"):
"""Get a gene's dependency slice from a dataset."""
url = f"{BASE_URL}/data/gene_dependency"
params = {"gene_name": gene_symbol, "dataset_name": dataset_name}
response = requests.get(url, params=params)
data = response.json()
return data
3. Download-Based Analysis (Recommended for Large Queries)

For large-scale analysis, download DepMap data files and analyze locally:

python
import pandas as pd
import requests, os
def download_depmap_data(url, output_path):
"""Download a DepMap data file."""
response = requests.get(url, stream=True)
with open(output_path, 'wb') as f:
for chunk in response.iter_content(chunk_size=8192):
f.write(chunk)
# DepMap 24Q4 data files (update version as needed)
FILES = {
"crispr_gene_effect": "https://figshare.com/ndownloader/files/...",
# OR download from: https://depmap.org/portal/download/all/
# Files available:
# CRISPRGeneEffect.csv - Chronos gene effect scores
# OmicsExpressionProteinCodingGenesTPMLogp1.csv - mRNA expression
# OmicsSomaticMutationsMatrixDamaging.csv - mutation binary matrix
# OmicsCNGene.csv - copy number
# sample_info.csv - cell line metadata
}
def load_depmap_gene_effect(filepath="CRISPRGeneEffect.csv"):
"""
Load DepMap CRISPR gene effect matrix.
Rows = cell lines (DepMap_ID), Columns = genes (Symbol (EntrezID))
"""
df = pd.read_csv(filepath, index_col=0)
# Rename columns to gene symbols only
df.columns = [col.split(" ")[0] for col in df.columns]
return df
def load_cell_line_info(filepath="sample_info.csv"):
"""Load cell line metadata."""
return pd.read_csv(filepath)
4. Identifying Selective Dependencies
python
import numpy as np
import pandas as pd
def find_selective_dependencies(gene_effect_df, cell_line_info, target_gene,
cancer_type=None, threshold=-0.5):
"""Find cell lines selectively dependent on a gene."""
# Get scores for target gene
if target_gene not in gene_effect_df.columns:
return None
scores = gene_effect_df[target_gene].dropna()
dependent = scores[scores <= threshold]
# Add cell line info
result = pd.DataFrame({
"DepMap_ID": dependent.index,
"gene_effect": dependent.values
}).merge(cell_line_info[["DepMap_ID", "cell_line_name", "primary_disease", "lineage"]])
if cancer_type:
result = result[result["primary_disease"].str.contains(cancer_type, case=False, na=False)]
return result.sort_values("gene_effect")
# Example usage (after loading data)
# df_effect = load_depmap_gene_effect("CRISPRGeneEffect.csv")
# cell_info = load_cell_line_info("sample_info.csv")
# deps = find_selective_dependencies(df_effect, cell_info, "KRAS", cancer_type="Lung")
5. Biomarker Analysis (Gene Effect vs. Mutation)
python
import pandas as pd
from scipy import stats
def biomarker_analysis(gene_effect_df, mutation_df, target_gene, biomarker_gene):
"""
Test if mutation in biomarker_gene predicts dependency on target_gene.
Args:
gene_effect_df: CRISPR gene effect DataFrame
mutation_df: Binary mutation DataFrame (1 = mutated)
target_gene: Gene to assess dependency of
biomarker_gene: Gene whose mutation may predict dependency
"""
if target_gene not in gene_effect_df.columns or biomarker_gene not in mutation_df.columns:
return None
# Align cell lines
common_lines = gene_effect_df.index.intersection(mutation_df.index)
scores = gene_effect_df.loc[common_lines, target_gene].dropna()
mutations = mutation_df.loc[scores.index, biomarker_gene]
mutated = scores[mutations == 1]
wt = scores[mutations == 0]
stat, pval = stats.mannwhitneyu(mutated, wt, alternative='less')
return {
"target_gene": target_gene,
"biomarker_gene": biomarker_gene,
"n_mutated": len(mutated),
"n_wt": len(wt),
"mean_effect_mutated": mutated.mean(),
"mean_effect_wt": wt.mean(),
"pval": pval,
"significant": pval < 0.05
}
6. Co-Essentiality Analysis
python
import pandas as pd
def co_essentiality(gene_effect_df, target_gene, top_n=20):
"""Find genes with most correlated dependency profiles (co-essential partners)."""
if target_gene not in gene_effect_df.columns:
return None
target_scores = gene_effect_df[target_gene].dropna()
correlations = {}
for gene in gene_effect_df.columns:
if gene == target_gene:
continue
other_scores = gene_effect_df[gene].dropna()
common = target_scores.index.intersection(other_scores.index)
if len(common) < 50:
continue
r = target_scores[common].corr(other_scores[common])
if not pd.isna(r):
correlations[gene] = r
corr_series = pd.Series(correlations).sort_values(ascending=False)
return corr_series.head(top_n)
# Co-essential genes often share biological complexes or pathways

Query Workflows

Workflow 1: Target Validation for a Cancer Type
  1. Download CRISPRGeneEffect.csv and sample_info.csv
  2. Filter cell lines by cancer type
  3. Compute mean gene effect for target gene in cancer vs. all others
  4. Calculate selectivity: how specific is the dependency to your cancer type?
  5. Cross-reference with mutation, expression, or CNA data as biomarkers
Workflow 2: Synthetic Lethality Screen
  1. Identify cell lines with mutation/deletion in gene of interest (e.g., BRCA1-mutant)
  2. Compute gene effect scores for all genes in mutant vs. WT lines
  3. Identify genes significantly more essential in mutant lines (synthetic lethal partners)
  4. Filter by selectivity and effect size
Workflow 3: Compound Sensitivity Analysis
  1. Download PRISM compound sensitivity data (primary-screen-replicate-treatment-info.csv)
  2. Correlate compound AUC/log2(fold-change) with genomic features
  3. Identify predictive biomarkers for compound sensitivity

DepMap Data Files Reference

FileDescription
CRISPRGeneEffect.csvCRISPR Chronos gene effect (primary dependency data)
CRISPRGeneEffectUnscaled.csvUnscaled CRISPR scores
RNAi_merged.csvDEMETER2 RNAi dependency
sample_info.csvCell line metadata (lineage, disease, etc.)
OmicsExpressionProteinCodingGenesTPMLogp1.csvmRNA expression
OmicsSomaticMutationsMatrixDamaging.csvDamaging somatic mutations (binary)
OmicsCNGene.csvCopy number per gene
PRISM_Repurposing_Primary_Screens_Data.csvDrug sensitivity (repurposing library)

Download all files from: https://depmap.org/portal/download/all/

Best Practices

  • Use Chronos scores (not DEMETER2) for current CRISPR analyses — better controlled for cutting efficiency
  • Distinguish pan-essential from cancer-selective: Target genes with low variance (essential in all lines) are poor drug targets
  • Validate with expression data: A gene not expressed in a cell line will score as non-essential regardless of actual function
  • Use DepMap ID for cell line identification — cell_line_name can be ambiguous
  • Account for copy number: Amplified genes may appear essential due to copy number effect (junk DNA hypothesis)
  • Multiple testing correction: When computing biomarker associations genome-wide, apply FDR correction

Additional Resources

  • DepMap Portal: https://depmap.org/portal/
  • Data downloads: https://depmap.org/portal/download/all/
  • DepMap paper: Behan FM et al. (2019) Nature. PMID: 30971826
  • Chronos paper: Dempster JM et al. (2021) Nature Methods. PMID: 34349281
  • GitHub: https://github.com/broadinstitute/depmap-portal
  • Figshare: https://figshare.com/articles/dataset/DepMap_24Q4_Public/27993966

Security

  • Security scanPassed, 95 of 100Pattern checks on the skill's files.
  • Model reviewPassed

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Source

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Stars and forks are for the whole GitHub repository, not this skill alone. Refreshed 10 Jun 2026, 5 months ago.

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