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OpEx - a validated, automated pipeline optimised for clinical exome sequence analysis

2016; Nature Portfolio; Volume: 6; Issue: 1 Linguagem: Inglês

10.1038/srep31029

2045-2322

Elise Ruark, Márton Münz, Matthew Clarke, Anthony Renwick, Emma Ramsay, Anna Elliott, Sheila Seal, Gerton Lunter, Nazneen Rahman,

Genomic variations and chromosomal abnormalities

Abstract We present an easy-to-use, open-source Op timised Ex ome 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.