Extended Data Fig. 1: Summary of the DDR and CIN loss-of-function screen of genome-doubling-associated drivers from the TRACERx 100 cohort.

a, Unsupervised clustering of the results from the DDR screen of 37 TRACERx drivers in 4 LUAD cell lines. Each row represents a DDR foci readout under a given genotoxic stress. Random forest classifiers were used to identify genes that had feature scores similar to positive controls; known DDR genes such as ATR, CHEK1, RAD51 and TP53BP1 are highlighted. Hierarchical clustering was used to calculate the Euclidean distance between TRACERx drivers and the known DDR positive control genes. b, HAC assay was used to assess the impact of gene depletion and mild replication stress on CIN, through modelling chromosome loss using an HT-1080 reporter system. Cells were processed and data was analysed as described in Methods. Data are displayed as scatter plots of log fold changes (LFCs) and Strictly Standardized Mean Difference (SSMDs), highlighting negative and positive control genes, and genes that passed the hit threshold (green area).