Distribution of substitutions and predicted mutation signatures. (A) Comparison of the distributions of the number of substitutions per patient in the cohort divided according to AIC cluster as indicated in the figure. (B) Left: pattern of substitutions in triplet context: observed across the cohort for genes identified as aSHM targets (upper panel), in the K1 signature described by Ye et al⁴⁰ (middle panel), and in the RCH signature described by Alkodsi et al⁴¹ (lower panel). The substitution type is indicated in the color-coded squares below the graph, with individual triplet contexts plotted by relative substitution frequency with matching color-coded bars. Right: cosine similarity measures. (C) Predicted mutational Reference Signature (RefSig) contribution to the substitution pattern observed in each sample using the Signal analysis package is displayed as a hierarchically clustered heatmap, divided by BIC FL clustering (color-coded bars above the heatmap). The percentage contribution of the predicted RefSig is indicated in the white (0) to red (100) color scale, as shown in the figure. Predicted contributing signatures are shown to the left. The distribution of predicted contributing signatures is shown to the right as a scatterplot. Note mutation signatures were derived from patterns observed in the lymphoma driver panel; cases with low mutation burden fall below the threshold for signature prediction.