Extended Data Fig. 2 ∣. Selected mutation features in relation to metabolite abundances.

a, Reduced glutathione (GSH) levels and the top correlated mutations among all mutational features. Cell lines are shown as lines and ordered by increasing levels of GSH. Those cell lines with corresponding mutations are labeled as black. The reported test statistics and p-values are based on the significance tests of genetic feature regression coefficients (cell line n=927, two-sided t-tests). b, Swarm plot comparing GSH, GSSG, and NADP⁺ levels in cell lines with or without KEAP1 mutations (n=72 and 855 respectively, mean ± SD). Each dot represents a cell line. The p-values were calculated based on two-sample t-tests (two-sided). c-h, Volcano plots comparing 225 profiled metabolites based on the mutational status of EGFR (c), KRAS (d), NRAS (e), TP53 (f), PTEN (g), TSC1/2 (h) in CCLE cell lines. Each point represents a metabolite and the red lines indicate a cutoff of q=0.05. The statistical significance and effect sizes were calculated using linear regression models conditioned on major lineage types (two sided t-test). Note that cell lines with either PTEN mutation or deletion were defined as PTEN deficient. i, Scatter plot comparing ME2 copy number alterations with its mRNA levels in all cell lines. j, Scatter plot comparing ME2 mRNA levels with malate levels in all cell lines. k, Scatter plot comparing ME2 mRNA levels with ME3 knockout CERES scores. For i-k, the p-values were calculated based on the significance test of Pearson correlations (two-sided). The number of cell lines used for analysis is shown above in each plot.