Allele-specific copy-number discovery from whole-genome and whole-exome sequencing.

TitleAllele-specific copy-number discovery from whole-genome and whole-exome sequencing.
Publication TypeJournal Article
Year of Publication2015
AuthorsWang, WeiBo, Wei Wang, Wei Sun, James J. Crowley, and Jin P. Szatkiewicz
JournalNucleic Acids Res
Volume43
Issue14
Paginatione90
Date Published2015 Aug 18
ISSN1362-4962
KeywordsAlgorithms, Alleles, DNA Copy Number Variations, Exome, Genomics, High-Throughput Nucleotide Sequencing, Humans, Sequence Analysis, DNA
Abstract

Copy-number variants (CNVs) are a major form of genetic variation and a risk factor for various human diseases, so it is crucial to accurately detect and characterize them. It is conceivable that allele-specific reads from high-throughput sequencing data could be leveraged to both enhance CNV detection and produce allele-specific copy number (ASCN) calls. Although statistical methods have been developed to detect CNVs using whole-genome sequence (WGS) and/or whole-exome sequence (WES) data, information from allele-specific read counts has not yet been adequately exploited. In this paper, we develop an integrated method, called AS-GENSENG, which incorporates allele-specific read counts in CNV detection and estimates ASCN using either WGS or WES data. To evaluate the performance of AS-GENSENG, we conducted extensive simulations, generated empirical data using existing WGS and WES data sets and validated predicted CNVs using an independent methodology. We conclude that AS-GENSENG not only predicts accurate ASCN calls but also improves the accuracy of total copy number calls, owing to its unique ability to exploit information from both total and allele-specific read counts while accounting for various experimental biases in sequence data. Our novel, user-friendly and computationally efficient method and a complete analytic protocol is freely available at https://sourceforge.net/projects/asgenseng/.

DOI10.1093/nar/gkv319
Alternate JournalNucleic Acids Res
Original PublicationAllele-specific copy-number discovery from whole-genome and whole-exome sequencing.
PubMed ID25883151
PubMed Central IDPMC4538801
Grant ListR01 GM105785 / GM / NIGMS NIH HHS / United States
HG006703 / HG / NHGRI NIH HHS / United States
MH090338 / MH / NIMH NIH HHS / United States
K01MH093517 / MH / NIMH NIH HHS / United States
R01CA082659 / CA / NCI NIH HHS / United States
U01CA105417 / CA / NCI NIH HHS / United States
U01CA134240 / CA / NCI NIH HHS / United States
K01MH094406 / MH / NIMH NIH HHS / United States
R01HG006292 / HG / NHGRI NIH HHS / United States
P01 CA142538 / CA / NCI NIH HHS / United States
Project: