Fig. 1. Overview of MuSiCal.

MuSiCal decomposes a mutation count matrix X into a signature matrix W and an exposure matrix H through four main modules: preprocessing, de novo discovery, matching and refitting, and in silico validation/optimization. The new methods implemented in each module are highlighted. Solid purple arrows represent a typical workflow of mutational signature analysis. Dashed orange arrows denote that some steps in the workflow potentially require repeating an earlier step (‘Results’).