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.
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:
Key resources:
depmap (or access via API/downloads)Use DepMap when:
| Score | Range | Meaning |
|---|---|---|
| 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 Effect | normalized | Normalized Chronos; −1 = median effect of common essential genes |
Key thresholds:
Each cell line has:
DepMap_ID: unique identifier (e.g., ACH-000001)cell_line_name: human-readable nameprimary_disease: cancer typelineage: broad tissue lineagelineage_subtype: specific subtypeimport 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()
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
For large-scale analysis, download DepMap data files and analyze locally:
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)
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")
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
}
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
CRISPRGeneEffect.csv and sample_info.csvprimary-screen-replicate-treatment-info.csv)| File | Description |
|---|---|
CRISPRGeneEffect.csv | CRISPR Chronos gene effect (primary dependency data) |
CRISPRGeneEffectUnscaled.csv | Unscaled CRISPR scores |
RNAi_merged.csv | DEMETER2 RNAi dependency |
sample_info.csv | Cell line metadata (lineage, disease, etc.) |
OmicsExpressionProteinCodingGenesTPMLogp1.csv | mRNA expression |
OmicsSomaticMutationsMatrixDamaging.csv | Damaging somatic mutations (binary) |
OmicsCNGene.csv | Copy number per gene |
PRISM_Repurposing_Primary_Screens_Data.csv | Drug sensitivity (repurposing library) |
Download all files from: https://depmap.org/portal/download/all/