Fig. 4

Different mutational signatures exhibit characteristic timing and strand asymmetry profiles. Columns show directional signature (column 1), distribution around timing transition regions (column 2), and around replication origins (column 3), per-patient mutation strand asymmetry (column 4; non-significant asymmetry is shown in light-colored histogram), and correlation with replication timing (column 5), as described in Fig. 3. The pie chart shows the proportional contributions by individual tissue types (number of samples weighted by their exposure) and the colors of the tissues are explain in the legend at the bottom. Row 1: signature 6, associated with mismatch-repair deficiency. Rows 2–3: signature 10, associated with POLE errors, shown for patients with known POLE mutations (row 2), and those without (row 3). Row 4: signature 7, representing UV-induced damage. Row 5: signature 17, characteristic of gastric and esophageal cancers. Row 6: signature 5, of unknown etiology, is not discernibly affected by replication