Abstract
MotivationIntegration of viruses into infected host cell DNA can cause DNA damage and disrupt genes. Recent cost reductions and growth of whole genome sequencing has produced a wealth of data in which viral presence and integration detection is possible. While key research and clinically relevant insights can be uncovered, existing software has not achieved widespread adoption, limited in part due to high computational costs, the inability to detect a wide range of viruses, as well as precision and sensitivity.ResultsHere, we describe VIRUSBreakend, a high-speed tool that identifies viral DNA presence and genomic integration. It utilizes single breakends, breakpoints in which only one side can be unambiguously placed, in a novel virus-centric variant calling and assembly approach to identify viral integrations with high sensitivity and a near-zero false discovery rate. VIRUSBreakend detects viral integrations anywhere in the host genome including regions such as centromeres and telomeres unable to be called by existing tools. Applying VIRUSBreakend to a large metastatic cancer cohort, we demonstrate that it can reliably detect clinically relevant viral presence and integration including HPV, HBV, MCPyV, EBV and HHV-8.Availability and implementationVIRUSBreakend is part of the Genomic Rearrangement IDentification Software Suite (GRIDSS). It is available under a GPLv3 license from https://github.com/PapenfussLab/VIRUSBreakend.Supplementary information Supplementary data are available at Bioinformatics online.
Highlights
As made abundantly clear by the SARS-CoV-2 and human immunodeficiency virus (HIV) pandemics, viral infections constitute a major worldwide threat to human health
Applying VIRUSBreakend to a large metastatic cancer cohort, we demonstrate that it can reliably detect clinically relevant viral presence and integration including human papillomavirus (HPV), Hepatitis B virus (HBV), Merkel cell polyomavirus (MCPyV), Epstein-Barr virus (EBV) and HHV-8
Viral integration sites were simulated by generating a fasta consisting of the 50kbp of host sequence before the insertion side, 2000 bp of HBV viral sequence, a 10 bp host gap, the 50kbp of host sequence after the insertion site
Summary
As made abundantly clear by the SARS-CoV-2 and HIV pandemics, viral infections constitute a major worldwide threat to human health. While most viruses do not integrate into the host genome, there is a significant global health burden caused by the subset of those that do, especially in cancer (McLaughlin-Drubin and Munger, 2008). HBV integrations in the TERT promoter region are associated with high telomerase expression and cancer cell survival (Zapatka et al, 2020). This integration site-specific behaviour is not just limited to oncogenic viruses, as human immunodeficiency virus (HIV) elite controllers have shown to have a high rate of centromeric viral integrations (Jiang et al, 2020). The reliable detection of viral integrations anywhere in the genome is key to understanding the effect of viral integration to disease
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