Genome-Wide Copy Number Variation Detection Using NGS: Data Analysis and Interpretation

Wei Shen; Philippe Szankasi; Jacob Durtschi; Todd W Kelley; Xinjie Xu

doi:10.1007/978-1-4939-9004-7_8

Genome-Wide Copy Number Variation Detection Using NGS: Data Analysis and Interpretation

Methods Mol Biol. 2019:1908:113-124. doi: 10.1007/978-1-4939-9004-7_8.

Authors

Wei Shen¹, Philippe Szankasi², Jacob Durtschi², Todd W Kelley¹, Xinjie Xu³

Affiliations

¹ Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT, USA.
² ARUP Laboratories, Salt Lake City, UT, USA.
³ Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT, USA. xinjie.xu@aruplab.com.

PMID: 30649724
DOI: 10.1007/978-1-4939-9004-7_8

Abstract

Copy number variants (CNVs) and copy neutral loss of heterozygosity (CN-LOH) represent important types of genomic abnormalities in cancer. Genomic DNA microarray serves as the current gold standard method for detecting genome-wide CNVs and CN-LOH. However, as next-generation sequencing (NGS) is widely used to detect gene variants in clinical testing, the ability of NGS to detect CNVs and CN-LOH has also been demonstrated. This chapter describes a protocol for detecting genome-wide large somatic CNVs and CN-LOH using a single nucleotide polymorphism (SNP) sequencing backbone. When combined with a targeted gene mutation panel, this strategy allows for simultaneous detection of somatic gene mutations and genome-wide CNVs and CN-LOH.

Keywords: B allele fraction; Circular binary segmentation algorithm (CBS); Copy number variants; Log2 ratio; Loss of heterozygosity; Next-generation sequencing; Read depth.

MeSH terms

DNA Copy Number Variations*
Data Analysis
Genomics / methods
High-Throughput Nucleotide Sequencing / methods*
Humans
Loss of Heterozygosity*
Mutation
Neoplasms / genetics*
Polymorphism, Single Nucleotide
Sequence Analysis, DNA / methods*
Software*