title: Using population data for assessing next-generation sequencing performance.
abstract: BACKGROUND
  During the past 4 years, whole-exome sequencing has become a standard tool for finding rare variants causing Mendelian disorders. In that time, there has also been a proliferation of both sequencing platforms and approaches to analyse their output. This requires approaches to assess the performance of different methods. Traditionally, criteria such as comparison with microarray data or a number of known polymorphic sites have been used. Here we expand such approaches, developing a maximum likelihood framework and using it to estimate the sensitivity and specificity of whole-exome sequencing data.
  
  
  RESULTS
  Using whole-exome sequencing data for a panel of 19 individuals, we show that estimated sensitivity and specificity are similar to those calculated using microarray data as a reference. We explore the effect of frequency misspecification arising from using an inappropriately selected population and find that, although the estimates are affected, the rankings across procedures remain the same.
  
  
  METHODS
  An implementation using Perl and R can be found at busso.ncl.ac.uk (Username: igm101; Password: Z1z1nts).
authors.affiliation: Oxford Gene Technology, Begbroke Science Park, Oxford, Oxfordshire, OX5 1PF, Institute of Genetic Medicine, Newcastle University, International Centre for Life, Central Parkway NE1 3BZ, Newcastle upon Tyne and The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
authors.forename: Darren T
authors.initials: DT
authors.lastname: Houniet
authors.affiliation: Oxford Gene Technology, Begbroke Science Park, Oxford, Oxfordshire, OX5 1PF, Institute of Genetic Medicine, Newcastle University, International Centre for Life, Central Parkway NE1 3BZ, Newcastle upon Tyne and The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
authors.forename: Thahira J
authors.initials: TJ
authors.lastname: Rahman
authors.affiliation: Oxford Gene Technology, Begbroke Science Park, Oxford, Oxfordshire, OX5 1PF, Institute of Genetic Medicine, Newcastle University, International Centre for Life, Central Parkway NE1 3BZ, Newcastle upon Tyne and The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
authors.forename: Saeed
authors.initials: S
authors.lastname: Al Turki
authors.affiliation: Oxford Gene Technology, Begbroke Science Park, Oxford, Oxfordshire, OX5 1PF, Institute of Genetic Medicine, Newcastle University, International Centre for Life, Central Parkway NE1 3BZ, Newcastle upon Tyne and The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Hurles
authors.affiliation: Oxford Gene Technology, Begbroke Science Park, Oxford, Oxfordshire, OX5 1PF, Institute of Genetic Medicine, Newcastle University, International Centre for Life, Central Parkway NE1 3BZ, Newcastle upon Tyne and The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
authors.forename: Yaobo
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Oxford Gene Technology, Begbroke Science Park, Oxford, Oxfordshire, OX5 1PF, Institute of Genetic Medicine, Newcastle University, International Centre for Life, Central Parkway NE1 3BZ, Newcastle upon Tyne and The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
authors.forename: Judith
authors.initials: J
authors.lastname: Goodship
authors.affiliation: Oxford Gene Technology, Begbroke Science Park, Oxford, Oxfordshire, OX5 1PF, Institute of Genetic Medicine, Newcastle University, International Centre for Life, Central Parkway NE1 3BZ, Newcastle upon Tyne and The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
authors.forename: Bernard
authors.initials: B
authors.lastname: Keavney
authors.affiliation: Oxford Gene Technology, Begbroke Science Park, Oxford, Oxfordshire, OX5 1PF, Institute of Genetic Medicine, Newcastle University, International Centre for Life, Central Parkway NE1 3BZ, Newcastle upon Tyne and The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK.
authors.forename: Mauro
authors.initials: M
authors.lastname: Santibanez Koref
mesh_terms: D000465:Algorithms; D019295:Computational Biology / Q000379:methods*; D059472:Exome / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics*; D005828:Genetics, Population; D015894:Genome, Human; D055106:Genome-Wide Association Study; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D018401:Sample Size