Figure 2

Mutational signatures identified in Bladder Cancer Genomes. (A) Heatmaps showing similarity between COSMIC signatures and mutational signatures that were de novo extracted from the TCGA bladder cancer dataset. Mutational signatures were identified using normalized (top heatmap) or raw (bottom heatmap) mutation counts. Cosine distances across signatures were computed, and displayed by color intensity. The yellow arrow indicates a signature that was specifically extracted when raw mutation counts were used as input. (B) Activity of mutational signatures extracted from raw mutation counts. A limited number (n = 30) of TCGA bladder cancer samples with the highest mutation burden is displayed. Each bar represents a tumor and the vertical axis denotes the number of mutations imputed to each signature (highlighted by colors). The leftmost bar of the plot (yellow bar) corresponds to the hyper-mutator sample (TCGA-DK-A6AW-01). (C) Barplots summarizing the mutational profiles of the sample (TCGA-DK-A6AW-01) and mutational signatures (blca_count_1, and COSMIC #10) corresponding to the hyper-mutator phenotype in cancer. Mutation types were grouped by SNV. Plots were generated using R software version 3.6.3 (R Core Team, 2020. R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. https://www.R-project.org/).