Figure 3

PCR duplicates inflate the false positive rate of differences between samples and alter measures of clonal heterogeneity. (A) False positive rate (FPR) for tests at heterozygous single nucleotide polymorphisms (SNPs) between groups of reads randomly allocated from the same sample with a varying percentage of simulated duplicates. Dotted line indicates FPR = 0.05. (B) Boxplot indicating higher variability in alternate allele frequency at heterozygous SNPs as duplication rate increases. (C) Increase in FPR for tests at heterozygous SNPs when single molecule tag-duplicates are present (black) or removed (grey). Dotted line indicates FPR = 0.05. (D) Estimates of the number of genetic clusters in two tumor samples (in red and blue respectively) becomes variable as duplicate rate increases. The number of clusters was calculated using PyClone.