Allelic decomposition and exact genotyping of highly polymorphic and structurally variant genes
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Author(s)
Malikić, Salem
Ford, Michael
Qin, Xiang
Toji, Lorraine
Radovich, Milan
Skaar, Todd C.
Pratt, Victoria M.
Scherer, Steve
Sahinalp, S. Cenk
Numanagic, Ibrahim
Date Issued
February 2018
Journal
Nature Communications
Publisher
Springer Nature
Citation
Numanagić, Ibrahim et al. “Allelic Decomposition and Exact Genotyping of Highly Polymorphic and Structurally Variant Genes.” Nature Communications 9, 1 (February 2018): 828 © 2018 The Author(s)
Version
Final published version
Abstract
High-throughput sequencing provides the means to determine the allelic decomposition for any gene of interest - the number of copies and the exact sequence content of each copy of a gene. Although many clinically and functionally important genes are highly polymorphic and have undergone structural alterations, no high-throughput sequencing data analysis tool has yet been designed to effectively solve the full allelic decomposition problem. Here we introduce a combinatorial optimization framework that successfully resolves this challenging problem, including for genes with structural alterations. We provide an associated computational tool Aldy that performs allelic decomposition of highly polymorphic, multi-copy genes through using whole or targeted genome sequencing data. For a large diverse sequencing data set, Aldy identifies multiple rare and novel alleles for several important pharmacogenes, significantly improving upon the accuracy and utility of current genotyping assays. As more data sets become available, we expect Aldy to become an essential component of genotyping toolkits.
MIT Department
Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory
Massachusetts Institute of Technology. Department of Mathematics
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Creative Commons Attribution 4.0 International License
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DOI of Published Version
https://doi.org/10.1038/S41467-018-03273-1
