Fig. 3. Practical consequences of increasing the mutational burden.

a As the number of mutations per sample increases, weights assigned to false positives decrease (relevant false positives: excess weights assigned to signatures active in the cohort; irrelevant false positives: weights assigned to signatures not active in the cohort). We used simulated input data with 100 samples and Stomach-AdenoCA signature weights. The reference signature catalog is COSMICv3 (top row) and the 18 signatures active in the Stomach-AdenoCA samples (bottom row). b Performance of four fitting methods in identifying systematic differences in mutational weights between two groups of samples (see Methods for details). The success rate is the fraction of 250 synthetic cohorts with artificially introduced differences in SBS40 weights between even- and odd-numbered samples where the estimated SBS40 weights differ significantly (Wilcoxon rank-sum test, p-value below 0.05). The error bars show the 95% confidence interval (Wilson score interval).