CODEX2: full-spectrum copy number variation detection by high-throughput DNA sequencing

• Published in: Genome Biology Vol. 19; no. 1; p. 202
• Main Authors: Jiang, Yuchao, Wang, Rujin, Urrutia, Eugene, Anastopoulos, Ioannis N, Nathanson, Katherine L, Zhang, Nancy R
• Format: Journal Article
• Language: English
• Published: England BioMed Central 26.11.2018; BMC
• Subjects: Bias; Bioinformatics; Biopsy; Cancer; Copy number; Copy number variation; Deoxyribonucleic acid; Disease; DNA; DNA Copy Number Variations; DNA sequencing; Genomes; Genomics - methods; High-Throughput Nucleotide Sequencing; Humans; Latent factor; Melanoma; Melanoma - genetics; Method; Mutation; Negative control; Next-generation sequencing; Normalization; Population; Latent factor; Normalization; Copy number variation; Next-generation sequencing; Negative control
• ISSN: 1474-760X; 1474-7596; 1474-760X
• DOI: 10.1186/s13059-018-1578-y

High-throughput DNA sequencing enables detection of copy number variations (CNVs) on the genome-wide scale with finer resolution compared to array-based methods but suffers from biases and artifacts that lead to false discoveries and low sensitivity. We describe CODEX2, as a statistical framework for full-spectrum CNV profiling that is sensitive for variants with both common and rare population frequencies and that is applicable to study designs with and without negative control samples. We demonstrate and evaluate CODEX2 on whole-exome and targeted sequencing data, where biases are the most prominent. CODEX2 outperforms existing methods and, in particular, significantly improves sensitivity for common CNVs.