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

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.

The Basis and Advances in Clinical Application of Cytomegalovirus-Specific Cytotoxic T Cell Immunotherapy for Glioblastoma Multiforme

“…Taking all of the controversies into account, a recent systematic review of 81 studies recruiting 7024 GB samples and 2420 blood samples revealed that HCMV is expressed in 36% and 45.2% of samples, respectively ( 108 ). Importantly, none of the healthy surrounding brain tissues employed as a control counterpart were detected to express HCMV genes or their products, indicating a high level of protection against off-tumor cytotoxicity for potential CMV-based immunotherapeutics for GB patients ( 72 , 109 – 112 ).…”

Presence of the Human Cytomegalovirus in Glioblastomas—A Systematic Review

“…In 7 studies, NGS was used to detect the HCMV in 681 tumors. DNA was sequenced in two of these studies [71,94]; RNA was sequenced in four [77,91,93,97]; and one was a metagenomic analysis [72]. None of these studies found evidence of HCMV nucleic acids (Table 7).…”

“…ISH was used in 15 studies of 339 tumor samples that included 18 analyses[2,36,44,50,52,54,56,61,63,66,76,78,87,95,96]. NGS was conducted in 681 tumor samples in 7 studies[71,72,77,91,93,94,97].…”

The Association of Human Herpesviruses with Malignant Brain Tumor Pathology and Therapy: Two Sides of a Coin

“…Recently, researchers aimed to detect CMV in 36 infantile brain tumors other than glioblastoma multiforme, and viral DNA was not detected in any of these tumors [ 27 ]. Furthermore, comprehensive assessment of the brain virome in 111 GBM tumors revealed the absence of CMV [ 28 ]. It was stated that the reason for the conflicting findings lies in the lack of sensitivity in the methods used by the different research groups.…”