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, 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 normalized single base substitution (SBS) matrix, or mutational signature. The normalized 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 a cosine similarity score ≥ 0.7 to the sample signature are analyzed using the deconstructSigs algorithm to determine the COSMIC mutational signatures with the highest cosine similarity to the sample.