Identification of Gene-Based Copy Number Variants Using Whole Exome Sequencing of Tumor Samples

• Activity Number: 254
• Type: Contributed
• Date/Time: Monday, August 10, 2015 : 2:00 PM to 3:50 PM
• Sponsor: Biometrics Section
• Author(s): Lun-Ching Chang* and Eric Polley
• Companies: National Cancer Institute and National Cancer Institute
• Keywords: WES ; CNV ; Cancer

Abstract

With the rapid advances of DNA sequencing technologies, whole exome sequencing (WES) has become a popular approach for detecting somatic mutations in oncology studies. The initial intent of the WES was to characterize single nucleotide variants and short insertions and deletions, but it was observed that the number of sequencing reads that mapped to a genomic region was correlated with the DNA copy number. Numerous methods for the normalization and copy number variant identification have been proposed that make use of this observation that read coverage correlates with copy number, but most current methods depend on a matched germline sample. We propose a method that doesn't require a matched normal sample, but instead we build a reference set that is used to estimate the distribution of the coverage for each exon. The construction of the reference set includes an evaluation on the sources of variability in the coverage distribution. We observed sample processing steps had an impact on the distribution of the coverage, and therefore recommend using the same sample processing and sequencing steps in the reference set as those that will be used on prospective samples. For each exon i