Agent skill
bio-tumor-fraction-estimation
Estimates circulating tumor DNA fraction from shallow whole-genome sequencing using ichorCNA. Detects copy number alterations via HMM segmentation and calculates ctDNA percentage. Requires 0.1-1x sWGS coverage. Use when quantifying tumor burden from liquid biopsy or monitoring treatment response.
Install this agent skill to your Project
npx add-skill https://github.com/FreedomIntelligence/OpenClaw-Medical-Skills/tree/main/skills/bio-tumor-fraction-estimation
SKILL.md
Version Compatibility
Reference examples tested with: CNVkit 0.9+, ichorCNA 0.5+, pandas 2.2+
Before using code patterns, verify installed versions match. If versions differ:
- Python:
pip show <package>thenhelp(module.function)to check signatures - R:
packageVersion('<pkg>')then?function_nameto verify parameters
If code throws ImportError, AttributeError, or TypeError, introspect the installed package and adapt the example to match the actual API rather than retrying.
Tumor Fraction Estimation
"Estimate tumor fraction from my cfDNA data" → Calculate the proportion of tumor-derived DNA in a liquid biopsy sample using copy number aberrations from shallow whole-genome sequencing.
- R:
ichorCNAfor tumor fraction and CNA estimation from sWGS
Estimate ctDNA tumor fraction from shallow whole-genome sequencing.
ichorCNA Overview
ichorCNA (GavinHaLab fork, v0.5.1+) detects copy number alterations and estimates tumor fraction from sWGS (0.1-1x coverage).
Sensitivity: 97-100% detection at >= 3% tumor fraction (2024 validation)
Input Requirements
| Requirement | Specification |
|---|---|
| Data type | sWGS (NOT targeted panel) |
| Coverage | 0.1-1x (0.5x recommended) |
| Input | BAM files |
| Output | Tumor fraction, ploidy, CNA segments |
Running ichorCNA
library(ichorCNA)
# Step 1: Generate read counts in bins
# Run from command line or use HMMcopy
# readCounter --window 1000000 --quality 20 sample.bam > sample.wig
# Step 2: Run ichorCNA
runIchorCNA(
WIG = 'sample.wig',
gcWig = 'gc_hg38_1mb.wig',
mapWig = 'mappability_hg38_1mb.wig',
normalPanel = 'pon_median_1mb.rds',
centromere = 'centromeres_hg38.txt',
outDir = 'ichor_results/',
id = 'sample_id',
# Tumor fraction estimation parameters
normal = c(0.5, 0.6, 0.7, 0.8, 0.9, 0.95, 0.99),
ploidy = c(2, 3),
maxCN = 5,
# Subclonality
estimateScPrevalence = TRUE,
scStates = c(1, 3),
# Segmentation
txnE = 0.9999,
txnStrength = 10000,
# Chromosomes
chrs = paste0('chr', c(1:22, 'X'))
)
Batch Processing
Goal: Run ichorCNA tumor fraction estimation on a cohort of sWGS samples in parallel, collecting results and handling failures gracefully.
Approach: Apply the ichorCNA pipeline to each sample's WIG file using mclapply for parallelization, wrapping each call in tryCatch to report per-sample success or failure.
library(ichorCNA)
library(parallel)
process_sample <- function(wig_file, params) {
sample_id <- basename(wig_file)
sample_id <- gsub('.wig$', '', sample_id)
tryCatch({
runIchorCNA(
WIG = wig_file,
gcWig = params$gcWig,
mapWig = params$mapWig,
normalPanel = params$normalPanel,
centromere = params$centromere,
outDir = params$outDir,
id = sample_id,
normal = c(0.5, 0.6, 0.7, 0.8, 0.9, 0.95, 0.99),
ploidy = c(2, 3),
maxCN = 5
)
return(list(sample = sample_id, status = 'success'))
}, error = function(e) {
return(list(sample = sample_id, status = 'failed', error = e$message))
})
}
# Run in parallel
wig_files <- list.files('wig/', pattern = '.wig$', full.names = TRUE)
params <- list(
gcWig = 'gc_hg38_1mb.wig',
mapWig = 'mappability_hg38_1mb.wig',
normalPanel = 'pon_median_1mb.rds',
centromere = 'centromeres_hg38.txt',
outDir = 'ichor_results/'
)
results <- mclapply(wig_files, process_sample, params = params, mc.cores = 4)
Parsing Results
parse_ichor_results <- function(results_dir) {
# Find results files
param_files <- list.files(results_dir, pattern = '.params.txt$',
full.names = TRUE, recursive = TRUE)
results <- data.frame()
for (f in param_files) {
params <- read.table(f, header = TRUE, sep = '\t', stringsAsFactors = FALSE)
sample_id <- gsub('.params.txt$', '', basename(f))
results <- rbind(results, data.frame(
sample = sample_id,
tumor_fraction = 1 - params$n[1], # n is normal fraction
ploidy = params$phi[1],
log_likelihood = params$loglik[1]
))
}
return(results)
}
# Parse all results
tf_results <- parse_ichor_results('ichor_results/')
print(tf_results)
Python Wrapper
import subprocess
import pandas as pd
from pathlib import Path
def run_ichorcna(wig_file, output_dir, gc_wig, map_wig, normal_panel, centromere):
'''Run ichorCNA from Python.'''
sample_id = Path(wig_file).stem
cmd = f'''
Rscript -e "
library(ichorCNA)
runIchorCNA(
WIG = '{wig_file}',
gcWig = '{gc_wig}',
mapWig = '{map_wig}',
normalPanel = '{normal_panel}',
centromere = '{centromere}',
outDir = '{output_dir}',
id = '{sample_id}',
normal = c(0.5, 0.6, 0.7, 0.8, 0.9, 0.95, 0.99),
ploidy = c(2, 3),
maxCN = 5
)
"
'''
subprocess.run(cmd, shell=True, check=True)
def parse_tumor_fraction(params_file):
'''Parse tumor fraction from ichorCNA output.'''
df = pd.read_csv(params_file, sep='\t')
return {
'tumor_fraction': 1 - df['n'].iloc[0],
'ploidy': df['phi'].iloc[0],
'log_likelihood': df['loglik'].iloc[0]
}
Interpretation
| Tumor Fraction | Interpretation |
|---|---|
| >= 10% | High ctDNA, reliable detection |
| 3-10% | Moderate ctDNA, detectable |
| < 3% | Low ctDNA, at detection limit |
| 0% | No detectable ctDNA or below LOD |
Related Skills
- cfdna-preprocessing - Preprocess BAMs before ichorCNA
- fragment-analysis - Complementary fragmentomics analysis
- ctdna-mutation-detection - Mutation detection from panel data
- copy-number/cnvkit-analysis - CNV concepts
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