Comment on "DNA damage is a pervasive cause of sequencing errors, directly confounding variant identification"

Even if the 8-oxo-G artifacts are twice the context-specific background level (i.e., GIVG_T 2), this corresponds to only a 5 to 10% increase in the overall base-level error rate (summed over all sequence contexts; Figure 1, A to C), which is less than the intersample variability of error rates at a fixed oxoQ. A 5% increase in the base-level error rate results in a minor, if any, increase in false-positive mutation calls (Figure 1, E and F), because calling algorithms are designed to handle typical levels of sequencing error. Only at GIVG_T 5 (equivalent to oxoQ 35) do the additional errors from 8-oxo-G become comparable to the sum of all other errors and have an adverse impact on variant calling. The vast majority of samples in TCGA exhibit only minor 8-oxo-G damage that has minimal impact on mutation calling. Consequently, the claim that 73% of TCGA sequencing runs have extensive damage is misleading.