Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

HPV, HBV, and HIV-1 Viral Integration Site Mapping: A Streamlined Workflow from NGS to Genomic Insights of Carcinogenesis

Version 1 : Received: 27 May 2024 / Approved: 28 May 2024 / Online: 28 May 2024 (11:55:16 CEST)

A peer-reviewed article of this Preprint also exists.

Shen-Gunther, J.; Easley, A. HPV, HBV, and HIV-1 Viral Integration Site Mapping: A Streamlined Workflow from NGS to Genomic Insights of Carcinogenesis. Viruses 2024, 16, 975. Shen-Gunther, J.; Easley, A. HPV, HBV, and HIV-1 Viral Integration Site Mapping: A Streamlined Workflow from NGS to Genomic Insights of Carcinogenesis. Viruses 2024, 16, 975.

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 Ge-nomics. 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 neigh-boring human genes that may play a crucial role in tumor development. Our results included in-formative 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.

Keywords

bioinformatics; HBV; HIV-1; HPV; hybrid capture NGS; insertional mutagenesis; next generation sequencing; oncovirus; virus taxonomy; virus database; viral mapping; virus integration

Subject

Biology and Life Sciences, Virology

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