Cypiripi

Exact genotyping of CYP2D6 using high-throughput sequencing data

Ibrahim Numanagić, Salem Malikić, Victoria M. Pratt, Todd Skaar, David A. Flockhart, S. Cenk Sahinalp

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Motivation: CYP2D6 is highly polymorphic gene which encodes the (CYP2D6) enzyme, involved in the metabolism of 20-25% of all clinically prescribed drugs and other xenobiotics in the human body. CYP2D6 genotyping is recommended prior to treatment decisions involving one or more of the numerous drugs sensitive to CYP2D6 allelic composition. In this context, high-throughput sequencing (HTS) technologies provide a promising time-efficient and cost-effective alternative to currently used genotyping techniques. To achieve accurate interpretation of HTS data, however, one needs to overcome several obstacles such as high sequence similarity and genetic recombinations between CYP2D6 and evolutionarily related pseudogenes CYP2D7 and CYP2D8, high copy number variation among individuals and short read lengths generated by HTS technologies. Results: In this work, we present the first algorithm to computationally infer CYP2D6 genotype at basepair resolution from HTS data. Our algorithm is able to resolve complex genotypes, including alleles that are the products of duplication, deletion and fusion events involving CYP2D6 and its evolutionarily related cousin CYP2D7. Through extensive experiments using simulated and real datasets, we show that our algorithm accurately solves this important problem with potential clinical implications.

Original languageEnglish (US)
Pages (from-to)i27-i34
JournalBioinformatics
Volume31
Issue number12
DOIs
StatePublished - Jun 15 2015

Fingerprint

Cytochrome P-450 CYP2D6
Sequencing
High Throughput
Throughput
Genotype
Drugs
Duplication
Metabolism
Recombination
Deletion
Genotyping Techniques
Resolve
Fusion
Enzymes
Fusion reactions
Technology
Genes
Pseudogenes
Gene
Xenobiotics

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Computational Theory and Mathematics
  • Computer Science Applications
  • Computational Mathematics
  • Statistics and Probability

Cite this

Numanagić, I., Malikić, S., Pratt, V. M., Skaar, T., Flockhart, D. A., & Sahinalp, S. C. (2015). Cypiripi: Exact genotyping of CYP2D6 using high-throughput sequencing data. Bioinformatics, 31(12), i27-i34. https://doi.org/10.1093/bioinformatics/btv232

Cypiripi : Exact genotyping of CYP2D6 using high-throughput sequencing data. / Numanagić, Ibrahim; Malikić, Salem; Pratt, Victoria M.; Skaar, Todd; Flockhart, David A.; Sahinalp, S. Cenk.

In: Bioinformatics, Vol. 31, No. 12, 15.06.2015, p. i27-i34.

Research output: Contribution to journalArticle

Numanagić, I, Malikić, S, Pratt, VM, Skaar, T, Flockhart, DA & Sahinalp, SC 2015, 'Cypiripi: Exact genotyping of CYP2D6 using high-throughput sequencing data', Bioinformatics, vol. 31, no. 12, pp. i27-i34. https://doi.org/10.1093/bioinformatics/btv232
Numanagić I, Malikić S, Pratt VM, Skaar T, Flockhart DA, Sahinalp SC. Cypiripi: Exact genotyping of CYP2D6 using high-throughput sequencing data. Bioinformatics. 2015 Jun 15;31(12):i27-i34. https://doi.org/10.1093/bioinformatics/btv232
Numanagić, Ibrahim ; Malikić, Salem ; Pratt, Victoria M. ; Skaar, Todd ; Flockhart, David A. ; Sahinalp, S. Cenk. / Cypiripi : Exact genotyping of CYP2D6 using high-throughput sequencing data. In: Bioinformatics. 2015 ; Vol. 31, No. 12. pp. i27-i34.
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