title: VarDict: a novel and versatile variant caller for next-generation sequencing in cancer research.
abstract: Accurate variant calling in next generation sequencing (NGS) is critical to understand cancer genomes better. Here we present VarDict, a novel and versatile variant caller for both DNA- and RNA-sequencing data. VarDict simultaneously calls SNV, MNV, InDels, complex and structural variants, expanding the detected genetic driver landscape of tumors. It performs local realignments on the fly for more accurate allele frequency estimation. VarDict performance scales linearly to sequencing depth, enabling ultra-deep sequencing used to explore tumor evolution or detect tumor DNA circulating in blood. In addition, VarDict performs amplicon aware variant calling for polymerase chain reaction (PCR)-based targeted sequencing often used in diagnostic settings, and is able to detect PCR artifacts. Finally, VarDict also detects differences in somatic and loss of heterozygosity variants between paired samples. VarDict reprocessing of The Cancer Genome Atlas (TCGA) Lung Adenocarcinoma dataset called known driver mutations in KRAS, EGFR, BRAF, PIK3CA and MET in 16% more patients than previously published variant calls. We believe VarDict will greatly facilitate application of NGS in clinical cancer research.
authors.affiliation: Oncology iMed, AstraZeneca, Waltham, MA 02451, USA Zhongwu.Lai@astrazeneca.com.
authors.forename: Zhongwu
authors.initials: Z
authors.lastname: Lai
authors.affiliation: Oncology iMed, AstraZeneca, Waltham, MA 02451, USA.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Markovets
authors.affiliation: Oncology iMed, AstraZeneca, Cambridge, CB2 0RE, UK.
authors.forename: Miika
authors.initials: M
authors.lastname: Ahdesmaki
authors.affiliation: Bioinformatics Core, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
authors.forename: Brad
authors.initials: B
authors.lastname: Chapman
authors.affiliation: Bioinformatics Core, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Bearsden Glasgow, G61 1QH, UK.
authors.forename: Oliver
authors.initials: O
authors.lastname: Hofmann
authors.affiliation: Oncology iMed, AstraZeneca, Cambridge, CB2 0RE, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: McEwen
authors.affiliation: Oncology iMed, AstraZeneca, Waltham, MA 02451, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Johnson
authors.affiliation: Oncology iMed, AstraZeneca, Waltham, MA 02451, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Dougherty
authors.affiliation: Oncology iMed, AstraZeneca, Waltham, MA 02451, USA.
authors.forename: J Carl
authors.initials: JC
authors.lastname: Barrett
authors.affiliation: Oncology iMed, AstraZeneca, Waltham, MA 02451, USA.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Dry
mesh_terms: D000483:Alleles; D019295:Computational Biology / Q000379:methods*; D005787:Gene Frequency; D014644:Genetic Variation; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D054643:INDEL Mutation; D019656:Loss of Heterozygosity; D008175:Lung Neoplasms / Q000235:genetics; D009369:Neoplasms / Q000235:genetics; D012372:ROC Curve; D012106:Research; D017422:Sequence Analysis, DNA; D012984:Software