title: Validation of a multiplex genotyping platform using a novel genomic database approach.
abstract: OBJECTIVE
  Technological advances now allow for multiplex platforms to simultaneously test many genetic conditions. Typically, such platforms are validated by assaying samples with known genotypes and/or phenotypes and/or with synthetic plasmids; however, these methods have limitations and with the inclusion of rarer diseases and mutations, we can no longer rely solely on them. We used a novel genomic database to validate an expanded genetic carrier screening platform.
  
  
  METHODS
  Our expanded carrier screening assay uses the Illumina Infinium iSelect HD Custom genotyping platform to test for 213 genetic diseases by assaying 1,663 pathogenic mutations. We leveraged two Coriell Institute biorepositories for validation: the Subcollection of Heritable Diseases and the 1000 Genomes Project.
  
  
  RESULTS
  We measured 12,394 mutation observations in 206 samples, resulting in 246 true positives, 12,147 true negatives, 1 false positive, and no false negatives. Results demonstrated high sensitivity (99.99%) and specificity (99.99%).
  
  
  CONCLUSIONS
  We successfully validated our platform with two biorepositories, demonstrating high sensitivity and specificity. The 1000 Genomes Project samples provided both positive and negative validation for mutations in genes not available through other biorepositories, expanding the depth of validated variants. We recommend including samples from the 1000 Genomes Project in the validation of future multiplex testing platforms.Genet Med advance online publication 30 July 2015Genetics in Medicine (2015); doi:10.1038/gim.2015.101.
authors.affiliation: Recombine, New York, New York, USA.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Rivera-Garcia
authors.affiliation: Recombine, New York, New York, USA.
authors.forename: Sara L
authors.initials: SL
authors.lastname: Bristow
authors.affiliation: Recombine, New York, New York, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Yarnall
authors.affiliation: Recombine, New York, New York, USA.
authors.forename: Neha
authors.initials: N
authors.lastname: Kumar
authors.affiliation: Recombine, New York, New York, USA.
authors.forename: Sally
authors.identifier: 0000000307774415
authors.initials: S
authors.lastname: Rodriguez
authors.affiliation: Recombine, New York, New York, USA.
authors.forename: Nicholas
authors.identifier: 0000000300738630
authors.initials: N
authors.lastname: De Veaux
authors.affiliation: Recombine, New York, New York, USA.
authors.forename: Alexander
authors.identifier: 0000000341206470
authors.initials: A
authors.lastname: Bisignano
authors.affiliation: Reprogenetics, Livingston, New Jersey, USA.
authors.forename: Bo
authors.identifier: 0000000236595670
authors.initials: B
authors.lastname: Chu
authors.affiliation: Reprogenetics, Livingston, New Jersey, USA.
authors.forename: Renata
authors.initials: R
authors.lastname: Prates
authors.affiliation: 1] Recombine, New York, New York, USA [2] Reprogenetics, Livingston, New Jersey, USA.
authors.forename: Santiago
authors.initials: S
authors.lastname: Munne