Similarly to our results with mtDNA, we have found that DS can help mitigate artifactual mutations derived from chemically damaged DNA. Numerous studies using NGS to sequence DNA from formalin-fixed tissues have reported a high number of false mutations34-36. Because complementary artifacts from damage events are unlikely to occur at the same corresponding position on paired DNA strands, the use of sequencing information from both strands to correct these errors makes DS extremely resistant to damage-induced misincorporations. By using DS, we have sequenced paired formalin-fixed and unfixed tissue samples, and we found only a twofold change in the mutation frequency, indicating that DS is useful for removing mutational artifacts even in extremely damaged and degraded DNA (M.J.P., E.J.F. and L.A.L., unpublished results).
