Figure 2. Relationship between DNA replication timing and substitution patterns.

The figure shows the proportions of different types of single nucleotide substitutions in the constant early (purple) and constant late (orange) DNA replication timing zones for completely sequenced genomes of five cancer types and two personal genomes: (A) melanoma of study 1²⁵, (B) melanoma of study 2²⁶, (C) prostate cancer²⁷, (D) small cell lung cancer²⁸, (E) chronic lymphocytic leukemia²⁹, (F) colorectal cancer³⁰, (G) Watson³¹ and (H) HuRef genomes³². The proportions were calculated based on the hg18 reference allele so that Prob(A→C: T→G) + Prob(A→G: T→C) + Prob(A→T: T→A) = 100%, and Prob(C→A: G→T) + Prob(C→T: G→A) + Prob(C→G: G→C) = 100% for each of the constant late and constant early categories. Note that A→T: T→A is a signature commonly higher in late replication timing in all cancer types. Using the Chi-squared test and correcting for multiple hypothesis testing by false discovery rate, (B), (C), (G) and (H) are significantly different with adjusted p-values less than 0.01.