Detecting and Estimating Contamination of Human DNA Samples in Sequencing and Array-Based Genotype Data Goo Jun, Matthew Flickinger, Kurt N. Hetrick,

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Detecting and Estimating Contamination of Human DNA Samples in Sequencing and Array-Based Genotype Data Goo Jun, Matthew Flickinger, Kurt N. Hetrick, Jane M. Romm, Kimberly F. Doheny, Gonçalo R. Abecasis, Michael Boehnke, Hyun Min Kang The American Journal of Human Genetics Volume 91, Issue 5, Pages 839-848 (November 2012) DOI: 10.1016/j.ajhg.2012.09.004 Copyright © 2012 The American Society of Human Genetics Terms and Conditions

Figure 1 SNP Genotype Calling and Estimation of Contamination from 299 European Sequenced Samples Across chromosome 20 (A) Numbers of heterozygous genotypes. (B) Ratio of the numbers of nonreference homozygous genotypes to heterozygous genotypes (HET/HOM ratio). (C) Estimated level of DNA sample contamination estimated from sequence data only. The American Journal of Human Genetics 2012 91, 839-848DOI: (10.1016/j.ajhg.2012.09.004) Copyright © 2012 The American Society of Human Genetics Terms and Conditions

Figure 2 Distribution of Array Intensity for Contaminated and Uncontaminated Samples BAF versus population MAF for (A) uncontaminated (α = 0) and (B) contaminated (α = 10%) samples. Normalized intensity plots for (C) uncontaminated (α = 0) and (D) contaminated (α = 10%) samples. The American Journal of Human Genetics 2012 91, 839-848DOI: (10.1016/j.ajhg.2012.09.004) Copyright © 2012 The American Society of Human Genetics Terms and Conditions

Figure 3 Estimated Contamination Levels for In Silico Contaminated Samples (A) Joint sequence and array-based method, (B) sequence-only method, and (C) between these two methods. The American Journal of Human Genetics 2012 91, 839-848DOI: (10.1016/j.ajhg.2012.09.004) Copyright © 2012 The American Society of Human Genetics Terms and Conditions

Figure 4 Estimated Versus Intended Contamination Levels from the Experimentally Contaminated Array Intensity Data Three methods—regression-based method, multisample mixture model method, and single-sample mixture model method—were compared in two populations (CEU and YRI). The American Journal of Human Genetics 2012 91, 839-848DOI: (10.1016/j.ajhg.2012.09.004) Copyright © 2012 The American Society of Human Genetics Terms and Conditions

Figure 5 Estimated Contamination Levels between Sequence-Based Methods Comparison of estimated contamination levels using sequence data with and without array genotype data for type 2 diabetes sequencing study. The American Journal of Human Genetics 2012 91, 839-848DOI: (10.1016/j.ajhg.2012.09.004) Copyright © 2012 The American Society of Human Genetics Terms and Conditions

Figure 6 Genotype Discordance between Sequence-Based and Array-Based Genotypes A function of estimated contamination level αˆ in the type 2 diabetes sequencing study; contamination level estimates based on the combined sequence and genotype array data, stratified by genotypes from HumanOmni2.5 array data. (A) Homozygous reference genotypes, (B) heterozygous genotypes, and (C) homozygous nonreference genotypes. The American Journal of Human Genetics 2012 91, 839-848DOI: (10.1016/j.ajhg.2012.09.004) Copyright © 2012 The American Society of Human Genetics Terms and Conditions