SearcHPV: A novel approach to identify and assemble human papillomavirus-host genomic integration events in cancer.
SearcHPV: A novel approach to identify and assemble human papillomavirus-host genomic integration events in cancer.
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DOI：
10.1002/cncr.33691
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发表时间：
2021-10-01
期刊：
影响因子：
6.2
通讯作者：
Brenner JC
中科院分区：
文献类型：
--
作者：
Pinatti LM;Gu W;Wang Y;Elhossiny A;Bhangale AD;Brummel CV;Carey TE;Mills RE;Brenner JC
人乳头瘤病毒（HPV）是一种公认的恶性转化的驱动程序，在许多部位，包括头颈部，宫颈，外阴，肛门直肠和阴茎鳞状细胞癌；然而，HPV整合到宿主人类基因组中对这一过程的影响在很大程度上仍未得到解决。这是由于确定HPV整合位点的技术挑战，其中包括现有信息学方法在从低读取覆盖率测序数据中发现病毒宿主断点方面的局限性。为了克服这一局限性，我们开发了一种新的基于靶向捕获技术的HPV检测管道SearcHPV，并将该算法应用于靶向捕获数据。我们使用全基因组链读测序对searchpv定义的断点进行了综合分析，以确定潜在的hpv相关结构变异。通过对HPV+模型的分析，我们发现SearcHPV检测HPV-宿主整合位点的灵敏度和特异性高于其他两种常用的HPV检测调用者。SearcHPV发现了已知癌症相关基因（包括TP63、MYC和TRAF2）附近的HPV整合位点，以及大结构变异区域附近的HPV整合位点。我们进一步验证了SearcHPV的连接组合体特征，这有助于准确识别病毒-宿主连接断点序列。我们发现病毒整合通过多种DNA修复机制发生，包括非同源末端连接、替代末端连接和微同源介导的修复。总之，我们表明SearcHPV是一种新的优化工具，可以从靶向捕获的DNA测序数据中准确检测hpv -人类整合位点。为了克服在人类乳头瘤病毒相关癌症中检测病毒整合的技术挑战，我们优化了一个名为SearcHPV的新管道。使用该工具，我们发现HPV+模型中基因附近的频繁整合和大结构重排区域。
Human papillomavirus (HPV) is a well-established driver of malignant transformation in a number of sites including head and neck, cervical, vulvar, anorectal and penile squamous cell carcinomas; however, the impact of HPV integration into the host human genome on this process remains largely unresolved. This is due to the technical challenge of identifying HPV integration sites, which includes limitations of existing informatics approaches to discover viral-host breakpoints from low read coverage sequencing data. To overcome this limitation, we developed a new HPV detection pipeline called SearcHPV based on targeted capture technology and applied the algorithm to targeted capture data. We performed an integrated analysis of SearcHPV-defined breakpoints with genome-wide linked read sequencing to identify potential HPV-related structural variations. Through analysis of HPV+ models, we show that SearcHPV detects HPV-host integration sites with a higher sensitivity and specificity than two other commonly used HPV detection callers. SearcHPV uncovered HPV integration sites adjacent to known cancer-related genes including TP63, MYC and TRAF2, as well as near regions of large structural variation. We further validated the junction contig assembly feature of SearcHPV, which helped to accurately identify viral-host junction breakpoint sequences. We found that viral integration occurred through a variety of DNA repair mechanisms including non-homologous end joining, alternative end joining and microhomology mediated repair. In summary, we show that SearcHPV is a new optimized tool for the accurate detection of HPV-human integration sites from targeted capture DNA sequencing data. To overcome technical challenges of detecting viral integrations in human papillomavirus-related cancers, we optimized a new pipeline called SearcHPV. Using this tool, we found frequent integration near genes and areas of large structural rearrangements in HPV+ models.
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影响因子：
5.3
作者：
Holmes A;Lameiras S;Jeannot E;Marie Y;Castera L;Sastre-Garau X;Nicolas A
通讯作者：
Nicolas A
影响因子：
--
作者：
Nulton TJ;Olex AL;Dozmorov M;Morgan IM;Windle B
通讯作者：
Windle B
影响因子：
3.7
作者：
Myers, J. E.;Guidry, J. T.;Scott, R. S.
通讯作者：
Scott, R. S.
影响因子：
3.8
作者：
Pannunzio NR;Li S;Watanabe G;Lieber MR
通讯作者：
Lieber MR
影响因子：
6.4
作者：
Bodelon C;Untereiner ME;Machiela MJ;Vinokurova S;Wentzensen N
通讯作者：
Wentzensen N