COSMOS: accurate detection of somatic structural variations through asymmetric comparison between tumor and normal samples.
COSMOS: accurate detection of somatic structural variations through asymmetric comparison between tumor and normal samples.
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DOI：
10.1093/nar/gkw026
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发表时间：
2016-05-05
影响因子：
14.9
通讯作者：
Sese J
中科院分区：
文献类型：
--
作者：
Yamagata K;Yamanishi A;Kokubu C;Takeda J;Sese J
癌症基因组学的一个重要挑战是通过高通量短读测序来精确检测结构变异（SVs），这受到现有分析工具高错误发现率的阻碍。在这里，我们提出了一种精确的SV检测方法，称为COSMOS，它以一种明显不对称的方式比较肿瘤样本和等基因正常对照样本中映射的读对的统计量。COSMOS还使用特定于链的读取深度信息对候选sv进行优先级排序。对模拟肿瘤基因组的性能测试表明，COSMOS在F-measure方面优于现有方法。我们还将COSMOS应用于基于小鼠细胞的实验模型，该模型通过基因组工程和伽马射线照射诱导sv，然后基于聚合酶链反应进行验证。COSMOS的精密度为84.5%，其次为70.4%。此外，COSMOS的灵敏度最高，表明COSMOS在癌症基因组分析方面具有很大的潜力。
An important challenge in cancer genomics is precise detection of structural variations (SVs) by high-throughput short-read sequencing, which is hampered by the high false discovery rates of existing analysis tools. Here, we propose an accurate SV detection method named COSMOS, which compares the statistics of the mapped read pairs in tumor samples with isogenic normal control samples in a distinct asymmetric manner. COSMOS also prioritizes the candidate SVs using strand-specific read-depth information. Performance tests on modeled tumor genomes revealed that COSMOS outperformed existing methods in terms of F-measure. We also applied COSMOS to an experimental mouse cell-based model, in which SVs were induced by genome engineering and gamma-ray irradiation, followed by polymerase chain reaction-based confirmation. The precision of COSMOS was 84.5%, while the next best existing method was 70.4%. Moreover, the sensitivity of COSMOS was the highest, indicating that COSMOS has great potential for cancer genome analysis.