Lai Zhongwu, Markovets Aleksandra, Ahdesmaki Miika, Chapman Brad, Hofmann Oliver, McEwen Robert, Johnson Justin, Dougherty Brian, Barrett J Carl, Dry Jonathan R
Oncology iMed, AstraZeneca, Waltham, MA 02451, USA
Oncology iMed, AstraZeneca, Waltham, MA 02451, USA.
Nucleic Acids Res. 2016 Jun 20;44(11):e108. doi: 10.1093/nar/gkw227. Epub 2016 Apr 7.
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.
在新一代测序（NGS）中进行准确的变异检测对于更好地理解癌症基因组至关重要。在此，我们展示了VarDict，这是一种适用于DNA测序数据和RNA测序数据的新型通用变异检测工具。VarDict能同时检测单核苷酸变异（SNV）、多核苷酸变异（MNV）、插入缺失（InDels）、复杂变异和结构变异，扩展了肿瘤中已检测到的遗传驱动因素范围。它能即时进行局部重比对，以更准确地估计等位基因频率。VarDict的性能随测序深度呈线性扩展，支持用于探索肿瘤进化或检测血液中循环肿瘤DNA的超深度测序。此外，VarDict对基于聚合酶链反应（PCR）的靶向测序进行扩增子感知变异检测，这种测序常用于诊断环境，并且能够检测PCR假象。最后，VarDict还能检测配对样本之间的体细胞变异和杂合性缺失变异的差异。对癌症基因组图谱（TCGA）肺腺癌数据集进行VarDict重新分析后，检测到KRAS、EGFR、BRAF、PIK3CA和MET中已知驱动突变的患者比之前发表的变异检测结果多16%。我们相信VarDict将极大地促进NGS在临床癌症研究中的应用。
