Title | Allele-specific copy-number discovery from whole-genome and whole-exome sequencing. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Wang, WeiBo, Wei Wang, Wei Sun, James J. Crowley, and Jin P. Szatkiewicz |
Journal | Nucleic Acids Res |
Volume | 43 |
Issue | 14 |
Pagination | e90 |
Date Published | 2015 Aug 18 |
ISSN | 1362-4962 |
Keywords | Algorithms, 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/. |
DOI | 10.1093/nar/gkv319 |
Alternate Journal | Nucleic Acids Res |
Original Publication | Allele-specific copy-number discovery from whole-genome and whole-exome sequencing. |
PubMed ID | 25883151 |
PubMed Central ID | PMC4538801 |
Grant List | R01 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 |
Allele-specific copy-number discovery from whole-genome and whole-exome sequencing.
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