title: Detecting and estimating contamination of human DNA samples in sequencing and array-based genotype data.
abstract: DNA sample contamination is a serious problem in DNA sequencing studies and may result in systematic genotype misclassification and false positive associations. Although methods exist to detect and filter out cross-species contamination, few methods to detect within-species sample contamination are available. In this paper, we describe methods to identify within-species DNA sample contamination based on (1) a combination of sequencing reads and array-based genotype data, (2) sequence reads alone, and (3) array-based genotype data alone. Analysis of sequencing reads allows contamination detection after sequence data is generated but prior to variant calling; analysis of array-based genotype data allows contamination detection prior to generation of costly sequence data. Through a combination of analysis of in silico and experimentally contaminated samples, we show that our methods can reliably detect and estimate levels of contamination as low as 1%. We evaluate the impact of DNA contamination on genotype accuracy and propose effective strategies to screen for and prevent DNA contamination in sequencing studies.
authors.affiliation: Department of Biostatistics and Center for Statistical Genetics, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Goo
authors.initials: G
authors.lastname: Jun
authors.forename: Matthew
authors.initials: M
authors.lastname: Flickinger
authors.forename: Kurt N
authors.initials: KN
authors.lastname: Hetrick
authors.forename: Jane M
authors.initials: JM
authors.lastname: Romm
authors.forename: Kimberly F
authors.initials: KF
authors.lastname: Doheny
authors.forename: Gonçalo R
authors.initials: GR
authors.lastname: Abecasis
authors.forename: Michael
authors.initials: M
authors.lastname: Boehnke
authors.forename: Hyun Min
authors.initials: HM
authors.lastname: Kang
mesh_terms: D059018:DNA Contamination; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000235:genetics; D005838:Genotype; D006801:Humans; D017422:Sequence Analysis, DNA