bio-clinical-databases-somatic-signatures

Version Compatibility

Reference examples tested with: MutationalPatterns 3.12+, SigProfilerExtractor 1.1+, numpy 1.26+

Before using code patterns, verify installed versions match. If versions differ:

• Python: pip show <package> then help(module.function) to check signatures
• R: packageVersion('<pkg>') then ?function_name to 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.

Somatic Mutational Signatures

"Extract mutational signatures from my tumor samples" → Decompose somatic mutation catalogs into mutational signatures (SBS, DBS, ID) to identify DNA damage mechanisms and mutagenic processes in cancer genomes.

• Python: SigProfilerExtractor.sigpro() for de novo signature extraction
• R: MutationalPatterns::fit_to_signatures() for fitting to COSMIC signatures

SigProfiler Workflow

Goal: Extract de novo mutational signatures and decompose to COSMIC reference signatures from somatic VCFs.

Approach: Generate a 96-trinucleotide-context mutation matrix with SigProfilerMatrixGenerator, extract signatures via NMF with SigProfilerExtractor, and fit to COSMIC with SigProfilerAssignment.

Install and Generate Matrix

from SigProfilerMatrixGenerator import install as genInstall
from SigProfilerMatrixGenerator.scripts import SigProfilerMatrixGeneratorFunc as matGen

# Install reference genome (one-time)
genInstall.install('GRCh38')

# Generate mutational matrix from VCF
# Input: Directory containing VCF files
# Output: SBS96 matrix (96 trinucleotide contexts)
matrices = matGen.SigProfilerMatrixGeneratorFunc(
    project='my_project',
    genome='GRCh38',
    vcfFiles='/path/to/vcf_directory',
    plot=True,
    exome=False  # Set True for WES
)

Extract Signatures

from SigProfilerExtractor import sigpro as sig

# De novo signature extraction
# Determines optimal number of signatures automatically
sig.sigProfilerExtractor(
    input_type='matrix',
    output='extraction_output',
    input_data='my_project/output/SBS/my_project.SBS96.all',
    reference_genome='GRCh38',
    minimum_signatures=1,
    maximum_signatures=10,
    nmf_replicates=100,
    cpu=-1  # Use all cores
)