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Chunk #18 — Results — Validation

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Absolute quantification of somatic DNA alterations in human cancer.
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We validated the purity and ploidy predictions made by ABSOLUTE on Affymetrix SNP microarray data using several approaches: (i) direct measurement of ploidy of 37 TCGA ovarian carcinoma samples by fluorescence-activated cell sorting 33 (Fig. 2a); (ii) Measurement of ploidy for 33 NCI60 cell lines based on spectral karyotyping34 (Fig. 2b,c); and (iii) DNA-mixing experiments, in which cancer cell lines were mixed with paired normal B-lymphocyte-derived DNAs in varying mass proportions (Fig. 2d, Online Methods). We also evaluated a related computational method, ASCAT30, on these data (Fig. 2a-d, Supplementary Note 1). Although the results were broadly concordant with our estimates, ABSOLUTE achieved significantly more accurate results (Fig. 2a-d) on our validation data. Notably, we observed an apparent bias by ASCAT to underestimate cancer cell fraction (Fig. 2 c,d), consistent with previous reports applying ASCAT in similar mixing experiments based on Illumina SNP arrays30, (Figure S4), suggesting that the bias is independent of measurement platform.