title: Comprehensive comparison of three commercial human whole-exome capture platforms.
abstract: BACKGROUND
  Exome sequencing, which allows the global analysis of protein coding sequences in the human genome, has become an effective and affordable approach to detecting causative genetic mutations in diseases. Currently, there are several commercial human exome capture platforms; however, the relative performances of these have not been characterized sufficiently to know which is best for a particular study.
  
  
  RESULTS
  We comprehensively compared three platforms: NimbleGen's Sequence Capture Array and SeqCap EZ, and Agilent's SureSelect. We assessed their performance in a variety of ways, including number of genes covered and capture efficacy. Differences that may impact on the choice of platform were that Agilent SureSelect covered approximately 1,100 more genes, while NimbleGen provided better flanking sequence capture. Although all three platforms achieved similar capture specificity of targeted regions, the NimbleGen platforms showed better uniformity of coverage and greater genotype sensitivity at 30- to 100-fold sequencing depth. All three platforms showed similar power in exome SNP calling, including medically relevant SNPs. Compared with genotyping and whole-genome sequencing data, the three platforms achieved a similar accuracy of genotype assignment and SNP detection. Importantly, all three platforms showed similar levels of reproducibility, GC bias and reference allele bias.
  
  
  CONCLUSIONS
  We demonstrate key differences between the three platforms, particularly advantages of solutions over array capture and the importance of a large gene target set.
authors.affiliation: Beijing Institute of Genomics, Chinese Academy of Sciences, No.7 Beitucheng West Road, Chaoyang District, Beijing 100029, China. asan@genomics.org.cn
authors.lastname: Asan
authors.forename: Yu
authors.initials: Y
authors.lastname: Xu
authors.forename: Hui
authors.initials: H
authors.lastname: Jiang
authors.forename: Chris
authors.initials: C
authors.lastname: Tyler-Smith
authors.forename: Yali
authors.initials: Y
authors.lastname: Xue
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.forename: Jiawei
authors.initials: J
authors.lastname: Wang
authors.forename: Mingzhi
authors.initials: M
authors.lastname: Wu
authors.forename: Xiao
authors.initials: X
authors.lastname: Liu
authors.forename: Geng
authors.initials: G
authors.lastname: Tian
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Huangming
authors.initials: H
authors.lastname: Yang
authors.forename: Xiuqing
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000483:Alleles; D001482:Base Composition; D059472:Exome; D030342:Genetic Diseases, Inborn / Q000235:genetics; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D008297:Male; D058977:Molecular Sequence Annotation; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods* / Q000592:standards; D016366:Open Reading Frames / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011933:Reagent Kits, Diagnostic / Q000592:standards*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA / Q000379:methods
chemical_list: D011933:Reagent Kits, Diagnostic