title: Performance of exome sequencing for pharmacogenomics.
abstract: OBJECTIVE
  We present the potential false-negative rate of exome sequencing for the detection of pharmacogenomic variants.
  
  
  METHODS
  Depth of coverage of 1928 pharmacogenomically relevant variant positions was ascertained from 62 exome-sequenced samples.
  
  
  RESULTS
  Approximately 14% of the 1928 variant locations examined had inadequate depth of coverage (<20x). The variants with inadequate coverage were predominantly located outside of protein-coding portions and included some clinically relevant variant positions, such as the warfarin VKORC1 variant.
  
  
  CONCLUSIONS
  While the use of exome sequencing is becoming more prevalent in fundamental research, clinical trials and clinical use; there is a possibility of false-negative results. The possible quality issues such as false-negative rate should be considered with the use of exome sequencing.
authors.affiliation: Department of Pathology, Anatomy & Cellular Biology, Computational Medicine Center, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA 19146, USA.
authors.forename: Eric R
authors.initials: ER
authors.lastname: Londin
authors.affiliation: Department of Pathology & Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Clark
authors.affiliation: Department of Internal Medicine & Medical Specialties, University of Rome "Sapienza", Rome, Italy.
authors.forename: Marialuisa
authors.initials: M
authors.lastname: Sponziello
authors.affiliation: Department of Pathology & Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, PA 19104, USA.
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Kricka
authors.affiliation: Cancer Genomics Laboratory, Department of Cancer Biology, Kimmel Cancer Center, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA 19146, USA ; Department of Molecular Medicine, University of Rome "Sapienza", Rome, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Fortina
authors.affiliation: Department of Pathology, University of Texas Southwestern Medical Center & Children's Medical Center, Dallas, TX 75235, USA ; Eugene McDermott Center for Human Growth & Development, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Jason Y
authors.initials: JY
authors.lastname: Park
keywords: exome sequencing; pharmacogenomics; warfarin