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Genome Biol. 2018 Nov 26;19(1):202. doi: 10.1186/s13059-018-1578-y.

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

Author information

1
Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, 27599, USA. yuchaoj@email.unc.edu.
2
Department of Genetics, School of Medicine, University of North Carolina, Chapel Hill, NC, 27599, USA. yuchaoj@email.unc.edu.
3
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, 27599, USA. yuchaoj@email.unc.edu.
4
Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, 27599, USA.
5
Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
6
Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
7
Department of Statistics, The Wharton School, University of Pennsylvania, Philadelphia, PA, 19104, USA. nzh@wharton.upenn.edu.

Abstract

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.

KEYWORDS:

Copy number variation; Latent factor; Negative control; Next-generation sequencing; Normalization

PMID:
30477554
PMCID:
PMC6260772
DOI:
10.1186/s13059-018-1578-y
[Indexed for MEDLINE]
Free PMC Article

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