Mutational Signature profiles

Cancer genomes are subject to diverse mutational processes that generate recognizable mutational signatures. Some processes are driven by defects in specific DNA repair pathways (for example, HRR, MMR) whereas others are characteristic of environmental mutagens (for example, ultra-violet light, tobacco smoke). These processes generate unique combinations of mutation types, a “Mutational Signature”.

Somatic SNVs in the sample are filtered to remove germline mutations and are used to construct a normalised single base substitution (SBS) matrix, or mutational signature. The normalised sample mutational signature is then compared with 54 signatures from the COSMIC Mutational Signatures v3.1 and the cosine similarity is calculated. COSMIC signatures with cosine similarity score ≥0.7 to the sample signature are then analyzed with the deconstructSigs algorithm to identify which COSMIC Mutational Signatures are the best match.