Virome assembly and annotation in brain tissue based on next-generation sequencing

Cancer Med. 2020 Sep;9(18):6776-6790. doi: 10.1002/cam4.3325. Epub 2020 Aug 1.

Abstract

The glioblastoma multiforme (GBM) is one of the deadliest tumors. It has been speculated that virus plays a role in GBM but the evidences are controversy. Published researches are mainly limited to studies on the presence of human cytomegalovirus (HCMV) in GBM. No comprehensive assessment of the brain virome, the collection of viral material in the brain, based on recently sequenced data has been performed. Here, we characterized the virome from 111 GBM samples and 57 normal brain samples from eight projects in the SRA database by a tested and comprehensive assembly approach. The annotation of the assembled contigs showed that most viral sequences in the brain belong to the viral family Retroviridae. In some GBM samples, we also detected full genome sequence of a novel picornavirus recently discovered in invertebrates. Unlike previous reports, our study did not detect herpes virus such as HCMV in GBM from the data we used. However, some contigs that cannot be annotated with any known genes exhibited antibody epitopes in their sequences. These findings provide several avenues for potential cancer therapy: the newly discovered picornavirus could be a starting point to engineer novel oncolytic virus; and the exhibited antibody epitopes could be a source to explore potential drug targets for immune cancer therapy. By characterizing the virosphere in GBM and normal brain at a global level, the results from this study strengthen the link between GBM and viral infection which warrants the further investigation.

Keywords: GBM; assembly; metagenomics.; virosphere.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain / pathology
  • Brain / virology*
  • Brain Neoplasms / pathology
  • Brain Neoplasms / virology*
  • Case-Control Studies
  • Contig Mapping
  • Databases, Nucleic Acid
  • Glioblastoma / pathology
  • Glioblastoma / virology*
  • High-Throughput Nucleotide Sequencing*
  • Humans
  • Metagenomics*
  • Picornaviridae / genetics*
  • RNA, Viral / genetics
  • RNA-Seq
  • Retroviridae / genetics*
  • Virome / genetics*

Substances

  • RNA, Viral