Fig. 4

TP53 loss phenocopy transcriptome scores predict drug sensitivity. a Our TP53 functional status classifier, derived from tumor data, is applied to cancer cell line data. Receiver operating characteristic (ROC curve and its area under curve (AUC) are shown. b The false discovery rate (FDR) for each cell line is shown as a dot. X axis represents the phenocopy score threshold at which each cell line would be classified as TP53 functionally deficient. Yellow horizontal bar represents the range for our definition of a high-confidence set of TP53 phenocopying cell lines (FDR = 0.18, threshold = 0.93). In the top part of the plot, cell lines harboring deletions of TP53, and amplifications of known phenocopying genes MDM4, MDM2 and PPM1D are marked. c TP53 status—drug sensitivity associations. Each panel represents the drugs targeting genes within a given pathway. Each dot represents an association of a drug with two possible TP53 functional status labels: X axis with the TP53 phenocopy score and Y axis with the TP53 mutational status (“CFE” labels by the GDSC, see Methods). P-values are from a pan-cancer regression test for association between a given drug log IC50 with the TP53 status. Associations with FDR < 0.25 are labeled. d Distributions of log IC50 values for several example drugs where TP53 status is known to confer resistance. The X axis illustrates the different categories based on TP53 mutated status (“Mutated TP53”), wild type TP53 (“Wild-type TP53”) and a high TP53 phenocopy score (“High confidence”); the “Mutated merge” is a combination of the two. P-values from statistical tests results comparing the groups (Mann–Whitney test, two-tailed) are plotted on top. Median values are provided inside each box