PDF(Pubmed)
Abstract：
Viral integration within the host genome plays a pivotal role in carcinogenesis. Various disruptive mechanisms are involved, leading to genomic instability, mutations, and DNA damage. With next-generation sequencing (NGS), we can now precisely identify viral and host genomic breakpoints and chimeric sequences, which are useful for integration site analysis. In this study, we evaluated a commercial hybrid capture NGS panel specifically designed for detecting three key viruses: HPV, HBV, and HIV-1. We also tested workflows for Viral Hybrid Capture (VHC) and Viral Integration Site (VIS) analysis, leveraging customized viral databases in CLC Microbial Genomics. By analyzing sequenced data from virally infected cancer cell lines (including SiHa, HeLa, CaSki, C-33A, DoTc2, 2A3, SCC154 for HPV; 3B2, SNU-182 for HBV; and ACH-2 for HIV-1), we precisely pinpointed viral integration sites. The workflow also highlighted disrupted and neighboring human genes that may play a crucial role in tumor development. Our results included informative virus-host read mappings, genomic breakpoints, and integration circular plots. These visual representations enhance our understanding of the integration process. In conclusion, our seamless end-to-end workflow bridges the gap in understanding viral contributions to cancer development, paving the way for improved diagnostics and treatment strategies.
摘要：
病毒在宿主基因组中的整合在癌变中起着关键作用。涉及各种破坏性机制，导致基因组不稳定，突变,和DNA损伤。通过下一代测序（NGS），我们现在可以精确地识别病毒和宿主基因组断点和嵌合序列，这对集成站点分析很有用。在这项研究中,我们评估了专门设计用于检测三种关键病毒的商业混合捕获NGS面板：HPV，HBV,HIV-1我们还测试了病毒混合捕获(VHC)和病毒集成站点(VIS)分析的工作流程，在CLC微生物基因组学中利用定制的病毒数据库。通过分析病毒感染的癌细胞系（包括SiHa，HeLa,CaSki,C-33A,DoTc2，2A3，SCC154用于HPV;3B2，SNU-182用于HBV;和ACH-2用于HIV-1），我们精确地确定了病毒整合位点。工作流程还强调了可能在肿瘤发展中起关键作用的破坏和邻近的人类基因。我们的结果包括信息丰富的病毒-宿主读取映射，基因组断点，和整合圆形地块。这些视觉表示增强了我们对集成过程的理解。总之,我们的无缝端到端工作流程弥合了理解病毒对癌症发展的贡献的差距，为改进诊断和治疗策略铺平道路。
