Fig. 5

Associations between drug response and genetic markers are commonly modified by TP53 functional status. a Identifying associations of mutations in various genes with antitumour drug sensitivity, controlling for TP53 status. Each panel represents a pathway targeted by drugs, and each dot represents a gene * drug *  cancer type combination. Associations are conditioned on TP53 status by including an interaction term in the regression, where the Y axis shows associations using TP53 mutated status using GDSC labels (TP53 CFEs), while the X axis represents the same using TP53 loss phenocopy score-based labels. Yellow-shaded area contains associations with FDR < 0.25 for TP53 phenocopy labels, and blue-shaded area shows the same for TP53 CFE labels. Total counts of significant associations in shaded areas are shown in the Venn diagram. b Association of PIK3CA mutation status with HDAC1-targeting drugs (AR-42 and CAY10603), after controlling for TP53 status. Large plots show the association without stratification by TP53 labels. “CFE” denotes mutated (Mut) or wild-type (WT) PIK3CA state. An association p-value above each box is by Mann–Whitney test. Each dot is a tumor sample belonging to one of the cancer types listed above the panel. Dots are colored according to TP53 phenocopy score labels. Small panels represent the same association but upon stratification by TP53 status; top row, stratification using TP53 phenocopy score labels; bottom row, using TP53 GDSC CFEs (“cancer functional events”, impactful mutation status, see Methods). The X axis represents tumor samples stratified by both the PIK3CA and TP53 status. PIK3CA status groups refer to PIK3CA stratification (WT, Mut) ignoring TP53 status. Labels should be interpreted as follows: “PIK3CA(WT/Mut) * TP53 (WT/Mut)” refers to stratification by PIK3CA status (CFE i.e. driver mutation status), using TP53 phenocopy labels (top) or TP53 CFEs (bottom). c Association of PTEN mutation status with ATR inhibitor drugs (AZD6738 and VE821), after controlling for TP53 status. Organization of the plots matches panel b.