Fig. 1: Signature activity trajectories for two samples.

Each plot is constructed from VAF data from a single tumour sample. Each line is an activity trajectory that depicts inferred activities for a single signature (y-axis) as a function of decreasing CCF (x-axis). The thin lines are trajectories from each of 30 bootstrap runs. The bold line depicts the mean activities across bootstraps. The vertical lines indicate time points in the original dataset, and are placed at the average CCF of their 100 associated mutations. Changes in activity trajectories are not necessarily aligned with vertical bars because mean CCFs of time points change across bootstraps. Frequency of changepoints between two vertical bars is indicated by shade, the darker shades indicate higher density of changepoints. Subclonal boundaries found by PCAWG consensus clustering²⁴ are shown in red vertical lines. These boundaries are not used in trajectory calculation and are only shown for comparison. Histograms show the mutation counts per signature in fixed width intervals of CCF. a Breast cancer sample. In clonal signatures remains constant with dominating signature 3 (associated with BRCA1 mutations). In the subclone activity to signature 3 decreases and is replaced by SNVs associated with APOBEC/AID (signatures 2 and 13). b Chronic lymphocytic leukaemia sample. Signature 9 (somatic hypermutation) dominates during clonal expansion and drops from 55% activity to almost zero in the subclone. Signature 5 compensates for this change.