Fig. 4: Determinants of cell line response to SJ3149.
a Boxplot of Pearson correlations between SJ3149 IC50 values and IC50 values of 120 anti-cancer agents in 102 cell lines. b Waterfall plots of cellular response to SJ3149 (left) and Nutlin-3a (right). Cell lines were colored based on the genomic status of TP53. Bars are based on the mean IC50 value as derived from duplicate 9-point dilution series for the 115 (SJ3149) or 102 (Nutlin-3a) cell lines. c Boxplot of Pearson correlations between basal expression levels of TP53, and IC50 values of SJ3149 and the 120 anti-cancer agents. Correlations are based on 99 or 95 cell lines for SJ3149 and the 120 other agents, respectively. d Volcano plot comparing the compound SJ3149 IC50 differences between cell lines harboring TP53 missense mutations. The green node indicates significantly lower IC50 in cell lines harboring a missense mutation on residue K132. Volcano plot of the Pearson correlations between drug IC50 values and CRISPR dependency scores of 17,453 genes in 77 cell lines for e Nutlin-3a and f SJ3149. Correlations are based on 78-cell lines. Plots in a, c–f were generated using 10log IC50 values (in nM) derived from duplicate 9-point dilution series for each cell line. For results in a, c, e, and f, correlations were determined using the ‘cor.test()’ function from the ‘stats’ package in R, using the Pearson method, pairwise complete observations, and two-sided alternative hypothesis. For results in d, the significance of IC50 shifts was determined by two-sided Type II ANOVA as implemented by the ‘Anova()’ function from the ‘car’ package in R. Benjamini–Hochberg multiple testing correction was performed using the ‘p.adjust()’ function from the ‘stats’ package in R. Adjusted p-values < 0.2 were considered significant. For the boxplots in a and c, bounds of boxes represent the first and third quartiles, the center indicates the median. Whiskers extend from the upper and lower bounds of the box to the largest or smallest value no further than 1.5 times the interquartile range. Outliers extending beyond these ranges are plotted individually.
