Allelic decomposition and exact genotyping of highly polymorphic and structurally variant genes

Ibrahim Numanagić, Salem Malikić, Michael Ford, Xiang Qin, Lorraine Toji, Milan Radovich, Todd C. Skaar, Victoria M. Pratt, Bonnie Berger, Steve Scherer, S. Cenk Sahinalp

Research output: Contribution to journalArticle

7 Scopus citations


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.

Original languageEnglish (US)
Article number828
JournalNature communications
Issue number1
StatePublished - Dec 1 2018


ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Numanagić, I., Malikić, S., Ford, M., Qin, X., Toji, L., Radovich, M., Skaar, T. C., Pratt, V. M., Berger, B., Scherer, S., & Sahinalp, S. C. (2018). Allelic decomposition and exact genotyping of highly polymorphic and structurally variant genes. Nature communications, 9(1), [828].