Tsakaneli Stavroula

Abstract

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease that affects approximately 2.8 million persons globally. While there is currently no cure for this neurodegenerative disease, MS has become a highly manageable disease through treatment options like disease-modifying medications, that can help to control the symptoms and slow disease progression. Among them, interferon beta (IFNβ) therapy is a first-line treatment for MS but has shown to be only partially effective. Thus, it is important to identify biomarkers that aid in early identification of IFNβ responders. In this study, based on gene expression profiles from untreated and interferon treated patients from a publicly available dataset, we performed differential expression analysis and Pigengene network association (weighted correlation network analysis (WGCNA) and Bayesian networks modeling) in order to construct a high-confidence protein-protein (PPI) interaction network. Subsequently, aiming to find the most significant clustering modules and hub genes, we applied a number of topological analysis methods (cytoHubba plugin) followed by MCODE clustering algorithm. Our approach resulted in highly connected hub genes generating a reliable 21-hubgene signature that could predict the response of interferon beta (IFNβ) therapy in patients with MS. The 21-hub-gene signature showed high classification performance (Accuracy = 91,49%, Sensitivity = 94.55%, Specificity = 87.15%) demonstrating potential clinical benefit.