Extended Data Fig. 4: Proportion of SBS mutations attributed to each mutational signature.

Signatures were selected using the ‘ColoRect-AdenoCa’ samples from the SigProfiler TCGA whole exome cohort (n = 496) (syn11801497.7). All signatures in the cohort with a non-zero mutation attribution were considered along with all MMR-deficiency signatures and platinum treatment signatures. Plots show the cohort wide signature attribution among (a) all 21 Prospect-C samples and (b) only in the PD tumors of the 12 patients with prolonged benefit. The red horizontal dashed line illustrates the 3% threshold used to define signatures as ‘active’ and the red box shows the signatures retained for subsequent analysis. SBS17a and SBS17b are described as ‘connected’ signatures¹⁵. SBS17a was retained due to the inclusion of SBS17b despite not reaching the threshold.