Fig. 1: Mutational fitting in multiple myeloma.

A Mutational profiles from two example patients with MM. B Mutational signature fitting reveals the main APOBEC signature (SBS2) along with the clock-like signatures SBS1 and SBS5 in both samples. Sample PD26419a (left) also had evidence of SBS13, which is most often detected in patients with high APOBEC mutational burden, as well as SBS8, a common mutational signature in MM that is of unknown etiology. Sample V0D58T (right) showed contributions from non-canonical activation-induced cytidine deaminase (nc-AID; SBS9), melphalan-induced mutagenesis (SBS-MM1), and damage by reactive oxygen species (ROS; SBS18). C To measure how well the fitted signatures account for the actual mutational profile in each sample, the first step is to reconstruct a mutational profile by multiplying the weight assigned to each signature with the reference profile of that signature. D Subtracting the reconstructed profile from the original profile illustrates which parts of the mutational spectrum are well-explained and may point to the presence of additional signatures that were not included in the analysis. In these cases, the mutational profiles were well-explained by the fitted signatures (high reconstruction accuracy), indicated by cosine similarity of >0.97 between observed and reconstructed profiles.