APOBEC-induced mutations in human cancers are strongly enriched on the lagging DNA strand during replication

Noncanonical mutation signatures of APOBEC3. Properties of TpCpS → TpKpS (noncanonical mutation type 1, nc1) (A,B) and TpCpN → TpApN (noncanonical mutation type 2, nc2) (C,D) induced by APOBEC3. (A,C) Correlations of enrichments of noncanonical (r_{apo_nc1} and r_{apo_nc2}) and canonical r_apo APOBEC3-induced mutations across tumors. (B,D) The ratio of the mutation rates of the considered mutation type to its reverse compliment on the reference strand as a function of the propensity of the replication fork to replicate the reference strand as lagging or leading. Horizontal axis in C and D: genome split by FP values into nine bins from low (bin 1) to high (bin 9). Vertical bars represent 95% confidence interval. Analysis performed using WGS data set.