Evaluation of Nine Somatic Variant Callers for Detection of Somatic Mutations in Exome and Targeted Deep Sequencing Data.
Evaluation of Nine Somatic Variant Callers for Detection of Somatic Mutations in Exome and Targeted Deep Sequencing Data.
复制标题
评估九个体细胞变体呼叫者，用于检测外显子和靶向深度测序数据中的体细胞突变。
DOI：
10.1371/journal.pone.0151664
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Larsen MJ
中科院分区：
文献类型：
--
作者：
Krøigård AB;Thomassen M;Lænkholm AV;Kruse TA;Larsen MJ
下一代测序广泛应用于癌症中的体细胞突变的分类，在研究环境中，并且越来越多地在临床环境中用于分子诊断，指导治疗决策。体细胞变异识别器对来自癌症组织和匹配的正常组织的测序数据进行配对比较，以检测体细胞突变。许多新的体细胞变异识别器的出现产生了对工具的比较和验证的需要，因为不存在用于检测体细胞突变的事实上的标准，并且仅报道了有限的比较。我们使用来自五名乳腺癌患者的配对肿瘤正常样本的外显子组测序和靶向深度测序数据进行了全面评估，以评估九种公开可用的体细胞变异调用程序的性能：EBCall，Mutect，Seurat，Shimmer，Indelocator，Somatic Sniper，Strelka，VarScan 2和Virmid用于检测单核苷酸突变和小缺失和插入。我们报告了在相同的测序数据和高度可变的一致性上，来自9个体细胞变异呼叫者的呼叫数量存在很大的变化。测序深度对个体识别者的影响差异显著，对于某些识别者，增加测序深度可显著提高灵敏度。对于SNV调用，我们报告EBCall、Mutect、Virmid和Strelka是外显子组测序和靶向深度测序的最可靠的体细胞变异调用者。对于插入缺失识别，EBCall由于对测序深度变化的高灵敏度和鲁棒性而具有上级优势。
Next generation sequencing is extensively applied to catalogue somatic mutations in cancer, in research settings and increasingly in clinical settings for molecular diagnostics, guiding therapy decisions. Somatic variant callers perform paired comparisons of sequencing data from cancer tissue and matched normal tissue in order to detect somatic mutations. The advent of many new somatic variant callers creates a need for comparison and validation of the tools, as no de facto standard for detection of somatic mutations exists and only limited comparisons have been reported. We have performed a comprehensive evaluation using exome sequencing and targeted deep sequencing data of paired tumor-normal samples from five breast cancer patients to evaluate the performance of nine publicly available somatic variant callers: EBCall, Mutect, Seurat, Shimmer, Indelocator, Somatic Sniper, Strelka, VarScan 2 and Virmid for the detection of single nucleotide mutations and small deletions and insertions. We report a large variation in the number of calls from the nine somatic variant callers on the same sequencing data and highly variable agreement. Sequencing depth had markedly diverse impact on individual callers, as for some callers, increased sequencing depth highly improved sensitivity. For SNV calling, we report EBCall, Mutect, Virmid and Strelka to be the most reliable somatic variant callers for both exome sequencing and targeted deep sequencing. For indel calling, EBCall is superior due to high sensitivity and robustness to changes in sequencing depths.