title: Cypiripi: exact genotyping of CYP2D6 using high-throughput sequencing data.
abstract: BACKGROUND
  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.
  
  
  METHODS
  Cypiripi is available at http://sfu-compbio.github.io/cypiripi.
authors.affiliation: School of Computing Science, Simon Fraser University, Burnaby, BC V5A 1S6, Canada, Department of Medicine, Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, IN 46202, USA and School of Informatics and Computing, Indiana University, Bloomington, IN 47401, USA School of Computing Science, Simon Fraser University, Burnaby, BC V5A 1S6, Canada, Department of Medicine, Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, IN 46202, USA and School of Informatics and Computing, Indiana University, Bloomington, IN 47401, USA.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Numanagić
authors.affiliation: School of Computing Science, Simon Fraser University, Burnaby, BC V5A 1S6, Canada, Department of Medicine, Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, IN 46202, USA and School of Informatics and Computing, Indiana University, Bloomington, IN 47401, USA School of Computing Science, Simon Fraser University, Burnaby, BC V5A 1S6, Canada, Department of Medicine, Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, IN 46202, USA and School of Informatics and Computing, Indiana University, Bloomington, IN 47401, USA.
authors.forename: Salem
authors.initials: S
authors.lastname: Malikić
authors.affiliation: School of Computing Science, Simon Fraser University, Burnaby, BC V5A 1S6, Canada, Department of Medicine, Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, IN 46202, USA and School of Informatics and Computing, Indiana University, Bloomington, IN 47401, USA.
authors.forename: Victoria M
authors.initials: VM
authors.lastname: Pratt
authors.affiliation: School of Computing Science, Simon Fraser University, Burnaby, BC V5A 1S6, Canada, Department of Medicine, Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, IN 46202, USA and School of Informatics and Computing, Indiana University, Bloomington, IN 47401, USA.
authors.forename: Todd C
authors.initials: TC
authors.lastname: Skaar
authors.affiliation: School of Computing Science, Simon Fraser University, Burnaby, BC V5A 1S6, Canada, Department of Medicine, Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, IN 46202, USA and School of Informatics and Computing, Indiana University, Bloomington, IN 47401, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Flockhart
authors.affiliation: School of Computing Science, Simon Fraser University, Burnaby, BC V5A 1S6, Canada, Department of Medicine, Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, IN 46202, USA and School of Informatics and Computing, Indiana University, Bloomington, IN 47401, USA School of Computing Science, Simon Fraser University, Burnaby, BC V5A 1S6, Canada, Department of Medicine, Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, IN 46202, USA and School of Informatics and Computing, Indiana University, Bloomington, IN 47401, USA.
authors.forename: S Cenk
authors.initials: SC
authors.lastname: Sahinalp
mesh_terms: D000483:Alleles; D019389:Cytochrome P-450 CYP2D6 / Q000145:classification* / Q000235:genetics*; D056915:DNA Copy Number Variations; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D011110:Polymorphism, Genetic / Q000235:genetics*; D011544:Pseudogenes; D012984:Software
chemical_list: D019389:Cytochrome P-450 CYP2D6