title: Allele-specific copy-number discovery from whole-genome and whole-exome sequencing.
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/.
authors.affiliation: Department of Computer Science, University of North Carolina at Chapel Hill, NC 27599-3175, USA.
authors.forename: WeiBo
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Computer Science, University of California, Los Angeles, CA 90095, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Biostatistics, University of North Carolina at Chapel Hill, NC 27599-7400, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.affiliation: Department of Genetics, University of North Carolina at Chapel Hill, NC 27599-7264, USA.
authors.forename: James J
authors.initials: JJ
authors.lastname: Crowley
authors.affiliation: Department of Genetics, University of North Carolina at Chapel Hill, NC 27599-7264, USA jin_szatkiewicz@med.unc.edu.
authors.forename: Jin P
authors.initials: JP
authors.lastname: Szatkiewicz
mesh_terms: D000465:Algorithms; D000483:Alleles; D056915:DNA Copy Number Variations; D059472:Exome; D023281:Genomics / Q000379:methods; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D017422:Sequence Analysis, DNA / Q000379:methods*