title: Personalized pharmacogenomics profiling using whole-genome sequencing.
abstract: OBJECTIVE
  Pharmacogenomics holds promise to rationalize drug use by minimizing drug toxicity and at the same time increase drug efficacy. There are currently several assays to screen for known pharmacogenomic biomarkers for the most commonly prescribed drugs. However, these genetic screening assays cannot account for other known or novel pharmacogenomic markers.
  
  
  METHODS
  We analyzed whole-genome sequences of 482 unrelated individuals of various ethnic backgrounds to obtain their personalized pharmacogenomics profiles.
  
  
  RESULTS
  Bioinformatics analysis revealed 408,964 variants in 231 pharmacogenes, from which 26,807 were residing on exons and proximal regulatory sequences, whereas 16,487 were novel. In silico analyses indicated that 1012 novel pharmacogene-related variants possibly abolish protein function. We have also performed whole-genome sequencing analysis in a seven-member family of Greek origin in an effort to explain the variable response rate to acenocoumarol treatment in two family members.
  
  
  CONCLUSIONS
  Overall, our data demonstrate that whole-genome sequencing, unlike conventional genetic screening methods, is necessary to determine an individual's pharmacogenomics profile in a more comprehensive manner, which, combined with the gradually decreasing whole-genome sequencing costs, would expedite bringing personalized medicine closer to reality.
authors.affiliation: Laboratory of Molecular Genetics, Department of Physiology & Biochemistry, University of Malta, Msida, Malta.
authors.forename: Clint
authors.initials: C
authors.lastname: Mizzi
authors.forename: Brock
authors.initials: B
authors.lastname: Peters
authors.forename: Christina
authors.initials: C
authors.lastname: Mitropoulou
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Mitropoulos
authors.forename: Theodora
authors.initials: T
authors.lastname: Katsila
authors.forename: Misha R
authors.initials: MR
authors.lastname: Agarwal
authors.forename: Ron H N
authors.initials: RH
authors.lastname: van Schaik
authors.forename: Radoje
authors.initials: R
authors.lastname: Drmanac
authors.forename: Joseph
authors.initials: J
authors.lastname: Borg
authors.forename: George P
authors.initials: GP
authors.lastname: Patrinos
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D019295:Computational Biology / Q000379:methods; D064420:Drug-Related Side Effects and Adverse Reactions / Q000235:genetics; D005820:Genetic Testing / Q000379:methods; D015894:Genome, Human; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D010597:Pharmacogenetics / Q000379:methods*; D057285:Precision Medicine / Q000379:methods*; D017422:Sequence Analysis, DNA / Q000379:methods
chemical_list: D015415:Biomarkers
keywords: drug metabolism; gene variants; personalized pharmacogenomics profile; pharmacogenomics; whole-genome sequencing