Concordance of copy number alterations using a common analytic pipeline for genome-wide analysis of Illumina and Affymetrix genotyping data: a report from the Children's Oncology Group

Marijana Vujkovic, Edward F. Attiyeh, Rhonda E. Ries, Michelle Horn, Elizabeth K. Goodman, Yang Ding, Marko Kavcic, Todd A. Alonzo, Robert B. Gerbing, Betsy Hirsch, Susana Raimondi, Alan S. Gamis, Soheil Meshinchi, Richard Aplenc

Copy number alterations (CNAs) are a hallmark of pediatric cancer genomes. An increasing number of research groups use multiple platforms and software packages to detect and analyze CNAs. However, different platforms have experimental and analysis-specific biases that may yield different results. We sought to estimate the concordance of CNAs in children with de novo acute myeloid leukemia between two experimental platforms: Affymetrix SNP 6.0 array and Illumina OmniQuad 2.5 BeadChip. Forty-five paired tumor-remission samples were genotyped on both platforms, and CNAs were estimated from total signal intensity and allelic contrast values using the allele-specific copy number analysis of tumors (ASCAT) algorithm. The two platforms were comparable in detection of CNAs, each missing only two segments from a total of 42 CNAs (4.6%). Overall, there was an interplatform agreement of 96% for allele-specific tumor profiles. However, poor quality samples with low signal/noise ratios showed a high rate of false-positive segments independent of the genotyping platform. These results demonstrate that a common analytic pipeline can be utilized for SNP array data from these two platforms. The customized programming template for the preprocessing, data integration, and analysis is publicly available at https://github.com/AplenCHOP/affyLumCNA.