Intersect-then-combine approach: improving the performance of somatic variant calling in whole exome sequencing data using multiple aligners and callers.
Intersect-then-combine approach: improving the performance of somatic variant calling in whole exome sequencing data using multiple aligners and callers.
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DOI：
10.1186/s13073-017-0425-1
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发表时间：
2017-04-18
期刊：
影响因子：
12.3
通讯作者：
Caldas C
中科院分区：
文献类型：
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作者：
Callari M;Sammut SJ;De Mattos-Arruda L;Bruna A;Rueda OM;Chin SF;Caldas C
对基因组测序数据进行生物信息学分析以识别癌症样品中的体细胞突变远未达到所需的稳健性和标准化。在这项研究中，我们使用铂基因组样本NA 12878生成了一个全外显子组测序基准数据集，并开发了一种交叉然后联合收割机（ITC）方法，以提高在肿瘤-正常对中识别单核苷酸变异（SNV）和插入缺失的准确性。我们评估了比对、碱基质量重新校准、突变识别器和过滤对灵敏度和假阳性率的影响。ITC方法将灵敏度提高至17.1%，而不会增加每兆碱基的假阳性率（FPR/Mb），并且其有效性在一组临床样本中得到了证实。本文的在线版本（doi：10.1186/s13073-017-0425-1）包含补充材料，可供授权用户使用。
Bioinformatic analysis of genomic sequencing data to identify somatic mutations in cancer samples is far from achieving the required robustness and standardisation. In this study we generated a whole exome sequencing benchmark dataset using the platinum genome sample NA12878 and developed an intersect-then-combine (ITC) approach to increase the accuracy in calling single nucleotide variants (SNVs) and indels in tumour-normal pairs. We evaluated the effect of alignment, base quality recalibration, mutation caller and filtering on sensitivity and false positive rate. The ITC approach increased the sensitivity up to 17.1%, without increasing the false positive rate per megabase (FPR/Mb) and its validity was confirmed in a set of clinical samples. The online version of this article (doi:10.1186/s13073-017-0425-1) contains supplementary material, which is available to authorized users.