Fig. 4: AM-1882 phenocopies KIF18A gene dependency across a panel of DNA-barcoded cancer cell lines.
a–f, Pooled cancer cell lines were treated with AM-1882 in a 5-d cell growth assay; the relative abundance of unique barcodes estimates cell viability (n = 1 experiment in triplicate). AM-1882 AUC values were determined for cancer cell lines (n = 631). a, Heatmap of the AM-1882 concentration–response profile; viability values for AM-1882 are presented as fold change relative to the DMSO control; a scale is shown on the right, with viability scoring as more sensitive (blue) or less sensitive (red). b, Violin plots show AM-1882 AUC distribution by tumor type (n = 24); numbers of cell lines per type are denoted on the x axis. The dotted line indicates an AUC value of 0.65, representing the lower-quartile (LQ) cutoff. c, AM-1882 AUC versus genome-wide gene dependency scores from RNAi KD (n ≤ 447 cell lines) or CRISPR KO (n ≤ 439 cell lines). Volcano plots show Pearson correlation scores and q values for 10,000 genes. KIF18A gene KD or KO was scored as the top-ranked correlation with AM-1882 sensitivity; other genes with positive or negative correlations with AM-1882 sensitivity are denoted in blue or red, respectively. d,e, AM-1882 AUC versus gene mutation (n = 629 cell lines). d, Volcano plot shows Pearson correlation scores and P values for 10,000 genes. TP53 gene mutation was scored as the top-ranked correlation with AM-1882 sensitivity. e, Scatterplot shows AM-1882 AUC versus TP53-WT or TP53-mutant group with mean AUC values for each group. The dashed line indicates an AUC value of 0.65. Statistical significance was determined for the TP53-WT group relative to the TP53-mutant group by unpaired two-tailed t-test (*Welch’s correction) and is shown as P values. f, AM-1882 AUC versus CIN features (WGD, DNA ploidy, AS) in breast and ovarian cancer cell lines (n = 58). Scatterplots show AM-1882 AUC versus TP53 status plus CIN features with mean AUC values for each group. Dashed lines indicate an AUC value of 0.65. Statistical significance was determined for CIN features in the TP53-mutant group by unpaired two-tailed t-test (*Welch’s correction) and is shown as P values. See supporting data (Extended Data Fig. 6 and Supplementary Tables 3–5).
