ScholarlyCommons

Title

CODEX: A Normalization and Copy Number Variation Detection Method for Whole Exome Sequencing

Author(s)

Yuchao Jiang
Derek A. Oldridge, University of Pennsylvania
Sharon J. Diskin, University of Pennsylvania
Nancy R. Zhang, University of Pennsylvania

Document Type

Technical Report

Date of this Version

3-31-2015

Publication Source

Nucleic Acids Research

Volume

43

Issue

6

Start Page

e39

DOI

10.1093/nar/gku1363

Abstract

High-throughput sequencing of DNA coding regions has become a common way of assaying genomic variation in the study of human diseases. Copy number variation (CNV) is an important type of genomic variation, but detecting and characterizing CNV from exome sequencing is challenging due to the high level of biases and artifacts. We propose CODEX, a normalization and CNV calling procedure for whole exome sequencing data. The Poisson latent factor model in CODEX includes terms that specifically remove biases due to GC content, exon capture and amplification efficiency, and latent systemic artifacts. CODEX also includes a Poisson likelihood-based recursive segmentation procedure that explicitly models the count-based exome sequencing data. CODEX is compared to existing methods on a population analysis of HapMap samples from the 1000 Genomes Project, and shown to be more accurate on three microarray-based validation data sets. We further evaluate performance on 222 neuroblastoma samples with matched normals and focus on a well-studied rare somatic CNV within the ATRX gene. We show that the cross-sample normalization procedure of CODEX removes more noise than normalizing the tumor against the matched normal and that the segmentation procedure performs well in detecting CNVs with nested structures.

Copyright/Permission Statement

© The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

Keywords

computational methods, genomics

Recommended Citation

Jiang, Y., Oldridge, D. A., Diskin, S. J., & Zhang, N. R. (2015). CODEX: A Normalization and Copy Number Variation Detection Method for Whole Exome Sequencing. Nucleic Acids Research, 43 (6), e39-. http://dx.doi.org/10.1093/nar/gku1363