Leveraging multi-omics approach in examining the potential role of causative viruses in glioblastoma.

Glioblastoma (GB) is a WHO grade 4 brain cancer with one of the lowest survival rates. Despite aggressive therapies, patient prognosis remains poor. The aetiology of GB is unclear, but some studies suggest pathogens may play a role in its pathogenesis. Infectious pathogens account for over 16% of global cancer incidence, with viruses linked to cancers like lymphomas, cervical cancer, and hepatocellular carcinoma. Many studies propose potential viral involvement in GB, but they often rely on a single technology, such as DNA/RNA sequencing or immunohistochemistry, limiting comprehensive understanding. Different technologies offer unique insights into GB's complex mechanisms, so using a combination of methods could provide a more thorough exploration of viral contributions. This project aims to investigate virome associations within the tumour microenvironment using a multi-omics approach: bioinformatics, metagenomics, and proteomics to detect and characterise viruses in GB. A preliminary study clarified the presence of viruses in GB by integrating three research methods. We screened 178 publicly accessible raw mass spectrometry data of GB tumours from three independent publications (PMID: 31331834, 31154438, 36720864) using an internally developed viral protein database to identify and analyse viral proteins. To enhance the dataset, we incorporated whole-genome metagenomics and MS-based proteomics, examining a small preliminary cohort of 15 GB tumour tissues (FFPE and Frozen). This comprehensive analysis identified multiple herpesvirus species across various cohorts, leveraging bioinformatics, genomics, and proteomics to explore viral-encoded proteins in GB. We are currently working on increasing the cohort of FFPE tumour tissues to further validate our findings.