Vy-PER: eliminating false positive detection of virus integration events in next generation sequencing data.
Vy-PER: eliminating false positive detection of virus integration events in next generation sequencing data.
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DOI：
10.1038/srep11534
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发表时间：
2015-07-13
影响因子：
4.6
通讯作者：
Franke A
中科院分区：
文献类型：
--
作者：
Forster M;Szymczak S;Ellinghaus D;Hemmrich G;Rühlemann M;Kraemer L;Mucha S;Wienbrandt L;Stanulla M;UFO Sequencing Consortium within I-BFM Study Group;Franke A
一些致病性病毒，如乙型肝炎和人类免疫缺陷病毒可能整合到宿主基因组中。这些病毒/宿主整合可通过下一代配对测序检测到。然而，低数量的预期真病毒整合可能很难从许多假阳性候选的噪音中区分出来。在这里，我们提出了一种新的过滤方法，在不影响病毒/宿主嵌合体检测灵敏度的情况下增加特异性。我们的检测管道称为Vy-PER（通过配对末端读取进行病毒集成检测），在速度和准确性方面优于现有的类似工具。我们分析了儿童急性淋巴细胞白血病（ALL）的全基因组数据，其特征是基因组重排，通常与辐射暴露有关。这一分析的动机是最近报道的基因组重排位点的病毒整合和肝癌中染色体不稳定性的关联。然而，正如预期的那样，我们对来自ALL患者的20个肿瘤和匹配的种系基因组的分析没有发现已知病毒整合的显著证据。尽管如此，我们的方法消除了每个基因组12,800个假阳性（80倍覆盖率），并且只有我们的方法检测到由Illumina HiSeq平台光学误差引起的单例human- phix174嵌合体。这种高准确性对于检测低病毒整合水平和非整合病毒非常有用。
Several pathogenic viruses such as hepatitis B and human immunodeficiency viruses may integrate into the host genome. These virus/host integrations are detectable using paired-end next generation sequencing. However, the low number of expected true virus integrations may be difficult to distinguish from the noise of many false positive candidates. Here, we propose a novel filtering approach that increases specificity without compromising sensitivity for virus/host chimera detection. Our detection pipeline termed Vy-PER (Virus integration detection bY Paired End Reads) outperforms existing similar tools in speed and accuracy. We analysed whole genome data from childhood acute lymphoblastic leukemia (ALL), which is characterised by genomic rearrangements and usually associated with radiation exposure. This analysis was motivated by the recently reported virus integrations at genomic rearrangement sites and association with chromosomal instability in liver cancer. However, as expected, our analysis of 20 tumour and matched germline genomes from ALL patients finds no significant evidence for integrations by known viruses. Nevertheless, our method eliminates 12,800 false positives per genome (80× coverage) and only our method detects singleton human-phiX174-chimeras caused by optical errors of the Illumina HiSeq platform. This high accuracy is useful for detecting low virus integration levels as well as non-integrated viruses.
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影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
3.7
作者：
Gautier, Laurent;Lund, Ole
通讯作者：
Lund, Ole
影响因子：
7
作者：
Jiang, Zhaoshi;Jhunjhunwala, Suchit;Zhang, Zemin
通讯作者：
Zhang, Zemin
影响因子：
5.4
作者：
Cruz, Cristian D.;Palosaari, Heidi;Horvath, Curt A.
通讯作者：
Horvath, Curt A.
影响因子：
20.3
作者：
Cook, Lucy B.;Rowan, Aileen G.;Bangham, Charles R. M.
通讯作者：
Bangham, Charles R. M.