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PSSV: a novel pattern-based probabilistic approach for somatic structural variation identification

机译:PSSV:体细胞结构变异识别的基于模式的新型概率方法

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摘要

>Motivation: Whole genome DNA-sequencing (WGS) of paired tumor and normal samples has enabled the identification of somatic DNA changes in an unprecedented detail. Large-scale identification of somatic structural variations (SVs) for a specific cancer type will deepen our understanding of driver mechanisms in cancer progression. However, the limited number of WGS samples, insufficient read coverage, and the impurity of tumor samples that contain normal and neoplastic cells, limit reliable and accurate detection of somatic SVs.>Results: We present a novel pattern-based probabilistic approach, PSSV, to identify somatic structural variations from WGS data. PSSV features a mixture model with hidden states representing different mutation patterns; PSSV can thus differentiate heterozygous and homozygous SVs in each sample, enabling the identification of those somatic SVs with heterozygous mutations in normal samples and homozygous mutations in tumor samples. Simulation studies demonstrate that PSSV outperforms existing tools. PSSV has been successfully applied to breast cancer data to identify somatic SVs of key factors associated with breast cancer development.>Availability and Implementation: An R package of PSSV is available at .>Contact: >Supplementary information: are available at Bioinformatics online.
机译:>动机:成对的肿瘤和正常样品的全基因组DNA测序(WGS)能够以前所未有的方式识别出体细胞DNA的变化。针对特定癌症类型的体细胞结构变异(SV)的大规模鉴定将加深我们对癌症进展中驱动机制的了解。但是,WGS样本数量有限,读取范围不足以及肿瘤样本中含有正常细胞和赘生性细胞的杂质限制了体细胞SV的可靠和准确检测。>结果:我们提出了一种新颖的模式-基于概率的方法PSSV,从WGS数据中识别体细胞结构变异。 PSSV具有混合模型,其隐藏状态代表不同的突变模式。因此,PSSV可以区分每个样品中的杂合和纯合SV,从而能够鉴定出正常样品中具有杂合突变而肿瘤样品中具有纯合突变的那些体细胞SV。仿真研究表明,PSSV的性能优于现有工具。 PSSV已成功应用于乳腺癌数据,以识别与乳腺癌发展相关的关键因素的体细胞SV。>可用性和实现:可从以下网站获得PSSV的R包:>联系方式: >补充信息:可在线访问生物信息学。

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