title: DNA damage is a pervasive cause of sequencing errors, directly confounding variant identification.
abstract: Mutations in somatic cells generate a heterogeneous genomic population and may result in serious medical conditions. Although cancer is typically associated with somatic variations, advances in DNA sequencing indicate that cell-specific variants affect a number of phenotypes and pathologies. Here, we show that mutagenic damage accounts for the majority of the erroneous identification of variants with low to moderate (1 to 5%) frequency. More important, we found signatures of damage in most sequencing data sets in widely used resources, including the 1000 Genomes Project and The Cancer Genome Atlas, establishing damage as a pervasive cause of sequencing errors. The extent of this damage directly confounds the determination of somatic variants in these data sets.
authors.affiliation: New England Biolabs Inc., 240 County Road, Ipswich, MA 01938-2723, USA.
authors.forename: Lixin
authors.identifier: 0000-0002-6165-9250
authors.initials: L
authors.lastname: Chen
authors.affiliation: New England Biolabs Inc., 240 County Road, Ipswich, MA 01938-2723, USA.
authors.forename: Pingfang
authors.identifier: 0000-0003-2126-7495
authors.initials: P
authors.lastname: Liu
authors.affiliation: New England Biolabs Inc., 240 County Road, Ipswich, MA 01938-2723, USA. evanst@neb.com ettwiller@neb.com.
authors.forename: Thomas C
authors.identifier: 0000-0001-5406-0146
authors.initials: TC
authors.lastname: Evans
authors.affiliation: New England Biolabs Inc., 240 County Road, Ipswich, MA 01938-2723, USA. evanst@neb.com ettwiller@neb.com.
authors.forename: Laurence M
authors.identifier: 0000-0002-3957-6539
authors.initials: LM
authors.lastname: Ettwiller
mesh_terms: D016477:Artifacts; D004249:DNA Damage; D004252:DNA Mutational Analysis / Q000592:standards* / Q000706:statistics & numerical data; D014644:Genetic Variation; D016045:Human Genome Project; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*