Exogene: A performant workflow for detecting viral integrations from paired-end next-generation sequencing data

PLoS One. 2021 Sep 22;16(9):e0250915. doi: 10.1371/journal.pone.0250915. eCollection 2021.


The integration of viruses into the human genome is known to be associated with tumorigenesis in many cancers, but the accurate detection of integration breakpoints from short read sequencing data is made difficult by human-viral homologies, viral genome heterogeneity, coverage limitations, and other factors. To address this, we present Exogene, a sensitive and efficient workflow for detecting viral integrations from paired-end next generation sequencing data. Exogene's read filtering and breakpoint detection strategies yield integration coordinates that are highly concordant with long read validation. We demonstrate this concordance across 6 TCGA Hepatocellular carcinoma (HCC) tumor samples, identifying integrations of hepatitis B virus that are also supported by long reads. Additionally, we applied Exogene to targeted capture data from 426 previously studied HCC samples, achieving 98.9% concordance with existing methods and identifying 238 high-confidence integrations that were not previously reported. Exogene is applicable to multiple types of paired-end sequence data, including genome, exome, RNA-Seq and targeted capture.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / virology*
  • Computational Biology / methods*
  • Hepatitis B / genetics*
  • Hepatitis B virus / physiology*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / virology*
  • Sequence Analysis, DNA
  • Sequence Analysis, RNA
  • Software
  • Virus Integration*
  • Whole Exome Sequencing
  • Workflow

Grant support

This study was funded by the Mayo Clinic Center for Individualized Medicine. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.