Fig. 3

Mutational enrichment analysis for patients with multiple biopsies in 5-FU treated and 5-FU untreated patients. a Example heat map of one patient showing the normalized mutation count of every mutation type from the first (above) and second (below) biopsy. This normalization step was performed on both samples of each patient. b Linear mixed model regression analysis on the normalized mutation counts of one mutation type (here T[T>G]C mutations) between patients that received a 5-FU treatment between the two biopsies and patients not treated with 5-FU between two biopsies (see also Supplementary Fig. 7). In the model, we controlled for exposure dose and time as well as other therapies that were administered to the patient between the first and second biopsy. P-values were obtained by performing an ANOVA test on the regression model. Box-and whiskers plot displays the first and the third quartiles (top and bottom of the box), the median (vertical line inside the box), the extremes (whiskers) and the single data points (single dots). c Bar plot showing the mutation type probability for COSMIC signature 17 with below the obtained P-values from the linear mixed model for every mutation type. Note that most of the mutation types that characterize COSMIC signature 17 show a significant increase in normalized mutation count for patients treated with 5-FU between both biopsies