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dc.contributor.authorRuark, Een_US
dc.contributor.authorHolt, Een_US
dc.contributor.authorRenwick, Aen_US
dc.contributor.authorMünz, Men_US
dc.contributor.authorWakeling, Men_US
dc.contributor.authorEllard, Sen_US
dc.contributor.authorMahamdallie, Sen_US
dc.contributor.authorYost, Sen_US
dc.contributor.authorRahman, Nen_US
dc.identifier.citationWellcome Open Res, 2018, 3 pp. 108 - ?en_US
dc.description.abstractEvaluating, optimising and benchmarking of next generation sequencing (NGS) variant calling performance are essential requirements for clinical, commercial and academic NGS pipelines. Such assessments should be performed in a consistent, transparent and reproducible fashion, using independently, orthogonally generated data. Here we present ICR142 Benchmarker, a tool to generate outputs for assessing germline base substitution and indel calling performance using the ICR142 NGS validation series, a dataset of Illumina platform-based exome sequence data from 142 samples together with Sanger sequence data at 704 sites. ICR142 Benchmarker provides summary and detailed information on the sensitivity, specificity and false detection rates of variant callers. ICR142 Benchmarker also automatically generates a single page report highlighting key performance metrics and how performance compares to widely-used open-source tools. We used ICR142 Benchmarker with VCF files outputted by GATK, OpEx and DeepVariant to create a benchmark for variant calling performance. This evaluation revealed pipeline-specific differences and shared challenges in variant calling, for example in detecting indels in short repeating sequence motifs. We next used ICR142 Benchmarker to perform regression testing with DeepVariant versions 0.5.2 and 0.6.1. This showed that v0.6.1 improves variant calling performance, but there was evidence of minor changes in indel calling behaviour that may benefit from attention. The data also allowed us to evaluate filters to optimise DeepVariant calling, and we recommend using 30 as the QUAL threshold for base substitution calls when using DeepVariant v0.6.1. Finally, we used ICR142 Benchmarker with VCF files from two commercial variant calling providers to facilitate optimisation of their in-house pipelines and to provide transparent benchmarking of their performance. ICR142 Benchmarker consistently and transparently analyses variant calling performance based on the ICR142 NGS validation series, using the standard VCF input and outputting informative metrics to enable user understanding of pipeline performance. ICR142 Benchmarker is freely available at
dc.format.extent108 - ?en_US
dc.subjectVariant callingen_US
dc.subjectfalse detection rateen_US
dc.subjectnext generation sequencingen_US
dc.titleICR142 Benchmarker: evaluating, optimising and benchmarking variant calling performance using the ICR142 NGS validation series.en_US
dc.typeJournal Article
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfWellcome Open Resen_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Genetic Susceptibility
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Genetic Susceptibility
pubs.publication-statusPublished onlineen_US
pubs.embargo.termsNot knownen_US
icr.researchteamGenetic Susceptibilityen_US
dc.contributor.icrauthorRahman, Saberaen_US

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