title: Determination of genotypes using a fully automated molecular detection system.
abstract: BACKGROUND
  Although the value of pharmacogenomics to improve patient outcomes has become increasingly clear, adoption in medical practice has been slow, which can be attributed to several factors, including complicated and expensive testing procedures and required equipment, lack of training by private practice physicians, and reluctance of both private and commercial payers to reimburse for such testing.
  
  
  OBJECTIVE
  To evaluate a fully automated molecular detection system for human genotyping assays, starting with anticoagulated whole blood samples, and to perform all sample preparation, assay, and analysis steps automatically with actionable results reported by the system's software.
  
  
  METHODS
  The genotypes of 254 random individuals were determined by performing bidirectional DNA sequencing, and that information was used to statistically train the imaging software of the automated molecular detection system to distinguish the 3 possible genotypes (ie, homozygous wild type, heterozygous, and homozygous mutant) at each of 3 different loci (CYP2C9*2, CYP2C9*3, and VKORC1).
  
  
  RESULTS
  The resulting software algorithm was able to correctly identify the genotypes of all 254 individuals (100%) evaluated without any further user analysis.
  
  
  CONCLUSIONS
  The EncompassMDx workstation (Rheonix, Inc, Ithaca, New York) is a molecular detection system that can automatically determine the genotypes of individuals in an unattended manner. Considerably less technical expertise was required to achieve results identical to those obtained using more complex, time-consuming, and expensive bidirectional DNA sequencing. This optimized system may dramatically simplify and reduce the costs of pharmacogenomics testing, thus leading to more-widespread use.
authors.affiliation: From Rheonix, Inc, Ithaca, New York (Drs Spizz, Chen, Li, McGuire, Zysling, Yasmin, Zhou, and Montagna; Mss Klimkiewicz and Hungerford; and Messrs Thomas, Mouchka, and Young); and the Department of Biostatistics, State University of New York, Buffalo (Dr Wilding). Dr Li is now with Thermo Fisher Scientific, San Francisco, California; Ms Klimkiewicz is now with the Rochester Institute of Technology, Rochester, New York; and Mr Young is now with INEng, LLC, Ithaca, New York.
authors.forename: Gwendolyn
authors.initials: G
authors.lastname: Spizz
authors.forename: Zongyuan
authors.initials: Z
authors.lastname: Chen
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.forename: I Cristina
authors.initials: IC
authors.lastname: McGuire
authors.forename: Paulina
authors.initials: P
authors.lastname: Klimkiewicz
authors.forename: Devin
authors.initials: D
authors.lastname: Zysling
authors.forename: Rubina
authors.initials: R
authors.lastname: Yasmin
authors.forename: Whitney
authors.initials: W
authors.lastname: Hungerford
authors.forename: Benjamin
authors.initials: B
authors.lastname: Thomas
authors.forename: Gregory
authors.initials: G
authors.lastname: Wilding
authors.forename: Gregory
authors.initials: G
authors.lastname: Mouchka
authors.forename: Lincoln
authors.initials: L
authors.lastname: Young
authors.forename: Peng
authors.initials: P
authors.lastname: Zhou
authors.forename: Richard A
authors.initials: RA
authors.lastname: Montagna
mesh_terms: D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics; D005838:Genotype; D060005:Genotyping Techniques / Q000295:instrumentation* / Q000379:methods*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods*; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results; D017422:Sequence Analysis, DNA / Q000379:methods*; D012984:Software; D064417:Vitamin K Epoxide Reductases / Q000235:genetics
chemical_list: D007527:Isoenzymes; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases