Fig. 3

APOBEC signatures in breast cancers show strong but distinct effects of replication. Column 1: directional signatures for the two APOBEC signatures, showing proportional contributions of individual mutation types (the absolute values sum to one). A maximum absolute value of 0.2 is shown and mutation types exceeding 0.2 are denoted by an asterisk. Column 2: mean signature exposure on the plus (Watson) and minus (Crick) strand around transitions between left- and right-replicating regions. The transition corresponds to a region enriched for replication origins. The bin size is 20 kbp. Column 3: mean signature exposure on the plus and minus strand around directly ascertained replication origins by SNS-seq, with a bin size of 1 kbp. Column 4: distribution of differences between matching and inverse exposure amongst patients with sufficient exposure. Number of outliers is denoted by the small numbers on the sides. Column 5: mean matching and inverse exposure in four quartiles of replication timing (p value is computed as signtest of slopes of correlation with replication timing in individual samples; the median values of the slope in the matching and inverse directions are shown on the right to the bars). The error bars represent standard error of the mean. The leading and lagging strand annotations used in columns 2, 4, and 5 are based on the direction of replication derived from replication timing data. Plots in columns 2–5 are based on samples not defined as outliers (by Tukey fences method with k = 2)