We’re excited to share our latest preprint, “VirTrack: A Framework for Inferring Viral Influence on Disease-Associated Transcriptomes — Clinical Type-Specific Epstein–Barr Virus Pathogenesis in Multiple Sclerosis,” now available on bioRxiv. This work, led by Dr. Anna Onisiforou, Head of our AI & Systems Bioinformatics Unit, represents a major advance in understanding how Epstein–Barr virus (EBV) contributes to Multiple Sclerosis across different disease stages. While the link between EBV and MS has been established during the last decade, how the virus influences the disease differently in early versus progressive forms has remained a critical unanswered question.

To address this, our team developed VirTrack, a novel computational framework that integrates experimentally validated EBV–host protein interactions with clinical type–specific gene expression data from patients with Clinically Isolated Syndrome, Relapsing Remitting MS, Secondary Progressive MS, and Primary Progressive MS. Using machine learning and systems biology approaches, VirTrack revealed striking clinical type–dependent patterns of viral engagement. In early MS stages, EBV targeted 13–18% of dysregulated genes, driving B-cell processes, inflammatory responses similar to active infection, and suppression of antiviral defenses. Remarkably, progressive forms showed a mechanistic shift: Secondary Progressive MS exhibited suppression of vascular and cardiac repair pathways, while Primary Progressive MS was characterized by upregulation of cellular remodeling processes. The framework also identified a stable core of influential viral proteins, with EBNA-LP consistently emerging as the top-ranked player across disease types.

This research, funded by the Infectious Diseases Society of America, has important therapeutic implications. Our findings suggest that EBV-directed interventions may be most effective in early disease stages when viral influence on immune dysregulation is strongest, while also revealing potential connections between EBV activity and vascular complications in progressive MS. Beyond MS, VirTrack offers a generalizable systems-level tool for investigating viral contributions to other complex human diseases, opening new avenues for understanding host-pathogen interactions across the disease spectrum.

To read the full article, please visit: https://doi.org/10.1101/2025.10.05.680499