title: OpEx - a validated, automated pipeline optimised for clinical exome sequence analysis.
abstract: We present an easy-to-use, open-source Optimised Exome analysis tool, OpEx (http://icr.ac.uk/opex) that accurately detects small-scale variation, including indels, to clinical standards. We evaluated OpEx performance with an experimentally validated dataset (the ICR142 NGS validation series), a large 1000 exome dataset (the ICR1000 UK exome series), and a clinical proband-parent trio dataset. The performance of OpEx for high-quality base substitutions and short indels in both small and large datasets is excellent, with overall sensitivity of 95%, specificity of 97% and low false detection rate (FDR) of 3%. Depending on the individual performance requirements the OpEx output allows one to optimise the inevitable trade-offs between sensitivity and specificity. For example, in the clinical setting one could permit a higher FDR and lower specificity to maximise sensitivity. In contexts where experimental validation is not possible, minimising the FDR and improving specificity may be a preferable trade-off for slightly lower sensitivity. OpEx is simple to install and use; the whole pipeline is run from a single command. OpEx is therefore well suited to the increasing research and clinical laboratories undertaking exome sequencing, particularly those without in-house dedicated bioinformatics expertise.
authors.affiliation: The Institute of Cancer Research, London, Division of Genetics &Epidemiology, Sutton SM2 5NG, UK.
authors.forename: Elise
authors.initials: E
authors.lastname: Ruark
authors.affiliation: Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK.
authors.forename: Márton
authors.initials: M
authors.lastname: Münz
authors.affiliation: The Institute of Cancer Research, London, Division of Genetics &Epidemiology, Sutton SM2 5NG, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Clarke
authors.affiliation: The Institute of Cancer Research, London, Division of Genetics &Epidemiology, Sutton SM2 5NG, UK.
authors.forename: Anthony
authors.initials: A
authors.lastname: Renwick
authors.affiliation: The Institute of Cancer Research, London, Division of Genetics &Epidemiology, Sutton SM2 5NG, UK.
authors.forename: Emma
authors.initials: E
authors.lastname: Ramsay
authors.affiliation: The Institute of Cancer Research, London, Division of Genetics &Epidemiology, Sutton SM2 5NG, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Elliott
authors.affiliation: The Institute of Cancer Research, London, Division of Genetics &Epidemiology, Sutton SM2 5NG, UK.
authors.forename: Sheila
authors.initials: S
authors.lastname: Seal
authors.affiliation: Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK.
authors.forename: Gerton
authors.initials: G
authors.lastname: Lunter
authors.affiliation: The Institute of Cancer Research, London, Division of Genetics &Epidemiology, Sutton SM2 5NG, UK.|Royal Marsden NHS Foundation Trust, Cancer Genetics Unit, Downs Road, Sutton, SM2 5PT, UK.
authors.forename: Nazneen
authors.initials: N
authors.lastname: Rahman