Extended Data Fig. 1: Mutational signatures of CX-5461 in isogenic hTERT-RPE1 cells.
From: The chemotherapeutic drug CX-5461 is a potent mutagen in cultured human cells
a. Distinguishing de novo mutational profiles of experimental subclones from controls. Light green, pink, and blue error bars (left to right) depict the mean ± 3SD of cosine similarities between n = 100 bootstrapped control profiles and the control mutational profile aggregated from n = 4 DMSO-treated control subclones, of respective mutation types with increasing mutation counts. The x axis displays the mutation counts for respective mutation classes. See Methods for details. b. Single base substitution (SBS) signatures of gene knockouts and CX-5461 in different knockout backgrounds. Background signature was derived from untreated RPE1 cells. c. Heatmap showing cosine similarities between experimental SBS signatures. d. Cosine similarities comparing SBS-CX-5461 and SBS-HRd to reference SBS signatures. e. in silico permutation to assess whether DBS-CX-5461 is a chance occurrence due to high mutation burden given SBS-CX-5461 pattern. DBS, double base substitution. f. Small insertion and deletion signatures associated with homologous recombination deficiency (HRd), etoposide (ETO), and CX-5461 exposure. InD-BRCA1 and InD-BRCA2 were identical (cosine similarity, 0.99), and hence averaged as InD-HRd. Background signature was derived from untreated RPE1 cells. g. Heatmap showing cosine similarities between experimental indel signatures (InDs).
