Transcriptomic analysis of Multiple Sclerosis patient-derived monocytes by RNA-Sequencing for candidate gene discovery

Abstract

Multiple Sclerosis (MS) is an inflammatory disorder associated with immune abnormalities in the Central Nervous System (CNS), including an abundance of monocytes in MS lesions. The molecular basis for this cellular response is still poorly understood. This study examined changes in the monocyte transcriptome occurring in patients with MS compared to healthy controls (HC) to identify genes that may improve diagnosis and help guide therapies. Unlike previous studies, which mainly utilized microarray technology, we used RNA-Sequencing (RNA-Seq) profiles to determine transcriptome changes, to identify affected pathways and functions, and to reveal the protein-protein interaction (PPI) networks. 4869 genes were significantly different between the two groups (16% upregulated and 17% downregulated). “Chemokine signaling” was the most significantly upregulated pathway. “Jak-STAT signaling,” “Toll-like receptor signaling,” “NOD-like receptor signaling,” “B cell receptor signaling,” “Apoptosis,” “Ubiquitin mediated proteolysis,” and “MAPK signaling” pathways were also significantly upregulated in MS. We also discovered novel candidate genes (RPS4Y1, XIST, DDX3Y, KDM5D, KDM6A, EIF1AY, UTY, TXLNGY, and PRKY) and pathways or pathways change (“Cell cycle,” “Osteoclast differentiation,” “ABC transporters,” “Complement and coagulation cascades,” “Fc gamma R-mediated phagocytosis,” and “Ribosome”) with potential MS implications. Finally, we proposed recommendations for future computational and experimental studies.

Keywords

• Multiple sclerosis
• RNA-Seq
• Monocytes
• Chemokine
• Differential gene expression
• KEGG