Extended Data Fig. 6. APOBEC3 deaminases drive acquisition of SBS2 and SBS13 in human cancer cells.

a,f,j) Mutational profiles of indicated clones plotted as numbers of genome-wide substitutions (y-axis) at cytosine bases classified into 48 possible trinucleotide sequence contexts (x-axis; detailed in Extended Data Fig. 4a). Arrows indicate the number of days spanning the cloning events of parents (left of arrow) and daughters (right), during which mutation acquisition was tracked. b) Numbers of SBS attributed to colour-coded mutational signatures discovered in indicated daughter clones. Q-values were calculated using one-tailed Mann-Whitney U-tests and FDR corrected using the Benjamini-Hochberg procedure.c,d,g,i,k) Focused plots showing indicated SBS2, SBS13a/b burdens in indicated daughter clones. e,h,l,m) Enrichment of cytosine mutations at APOBEC3B-preferred RTCA and APOBEC3A-preferred YTCA sequence contexts (R = purine base, Y = pyrimidine base, N = any base) in daughter clones from indicated cell lines and genotypes. m) Quantification of DDOST 558C>U levels in the indicated HT-1376 cells. Bars represent the mean of 3 technical replicates and n = 2 experiments. Clones marked in red across panels were excluded from statistical tests (Methods).