Extended Data Fig. 4: Mutation signature analysis in the SU2C-MARK and TCGA-LCNE cohorts.

(a) Unsupervised mutational signature identification was performed using automatic relevance determination non-negative matrix factorization (ARD-NMF) on the combined SU2C-MARK and TCGA-LCNE cohorts. The TCGA-LCNE cohort comprises TCGA lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), and published large cell neuroendocrine (LCNE)⁶³ cohorts. Of the 7 signatures identified, the predominant signatures corresponded to COSMIC signatures for Aging (SBS5), Smoking (SBS4), and APOBEC (SBS13). Plots display mutational signatures identified in each sample based on mutation counts (left) as well as fraction of signature attributable mutations (right) with a shared color key for both plots. (b) Barplot of signature profiles demonstrating relative contribution from each 96-base context. Signatures were subsequently assigned to previously described COSMIC signatures based on cosine similarity⁸⁴.