title: Systematic pharmacogenomics analysis of a Malay whole genome: proof of concept for personalized medicine.
abstract: BACKGROUND
  With a higher throughput and lower cost in sequencing, second generation sequencing technology has immense potential for translation into clinical practice and in the realization of pharmacogenomics based patient care. The systematic analysis of whole genome sequences to assess patient to patient variability in pharmacokinetics and pharmacodynamics responses towards drugs would be the next step in future medicine in line with the vision of personalizing medicine.
  
  
  METHODS
  Genomic DNA obtained from a 55 years old, self-declared healthy, anonymous male of Malay descent was sequenced. The subject's mother died of lung cancer and the father had a history of schizophrenia and deceased at the age of 65 years old. A systematic, intuitive computational workflow/pipeline integrating custom algorithm in tandem with large datasets of variant annotations and gene functions for genetic variations with pharmacogenomics impact was developed. A comprehensive pathway map of drug transport, metabolism and action was used as a template to map non-synonymous variations with potential functional consequences.
  
  
  RESULTS
  Over 3 million known variations and 100,898 novel variations in the Malay genome were identified. Further in-depth pharmacogenetics analysis revealed a total of 607 unique variants in 563 proteins, with the eventual identification of 4 drug transport genes, 2 drug metabolizing enzyme genes and 33 target genes harboring deleterious SNVs involved in pharmacological pathways, which could have a potential role in clinical settings.
  
  
  CONCLUSIONS
  The current study successfully unravels the potential of personal genome sequencing in understanding the functionally relevant variations with potential influence on drug transport, metabolism and differential therapeutic outcomes. These will be essential for realizing personalized medicine through the use of comprehensive computational pipeline for systematic data mining and analysis.
authors.affiliation: Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA (UiTM) Malaysia, Puncak Alam, Selangor, Malaysia. zakisalleh@puncakalam.uitm.edu.my
authors.forename: Mohd Zaki
authors.initials: MZ
authors.lastname: Salleh
authors.forename: Lay Kek
authors.initials: LK
authors.lastname: Teh
authors.forename: Lian Shien
authors.initials: LS
authors.lastname: Lee
authors.forename: Rose Iszati
authors.initials: RI
authors.lastname: Ismet
authors.forename: Ashok
authors.initials: A
authors.lastname: Patowary
authors.forename: Kandarp
authors.initials: K
authors.lastname: Joshi
authors.forename: Ayesha
authors.initials: A
authors.lastname: Pasha
authors.forename: Azni Zain
authors.initials: AZ
authors.lastname: Ahmed
authors.forename: Roziah Mohd
authors.initials: RM
authors.lastname: Janor
authors.forename: Ahmad Sazali
authors.initials: AS
authors.lastname: Hamzah
authors.forename: Aishah
authors.initials: A
authors.lastname: Adam
authors.forename: Khalid
authors.initials: K
authors.lastname: Yusoff
authors.forename: Boon Peng
authors.initials: BP
authors.lastname: Hoh
authors.forename: Fazleen Haslinda Mohd
authors.initials: FH
authors.lastname: Hatta
authors.forename: Mohamad Izwan
authors.initials: MI
authors.lastname: Ismail
authors.forename: Vinod
authors.initials: V
authors.lastname: Scaria
authors.forename: Sridhar
authors.initials: S
authors.lastname: Sivasubbu
mesh_terms: D044466:Asian People / Q000235:genetics*; D015415:Biomarkers; D002874:Chromosome Mapping; D019295:Computational Biology; D005260:Female; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D055106:Genome-Wide Association Study; D023281:Genomics; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008296:Malaysia; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics / Q000379:methods*; D020641:Polymorphism, Single Nucleotide; D057285:Precision Medicine; D040641:Quantitative Trait Loci; D019655:Quantitative Trait, Heritable
chemical_list: D015415:Biomarkers