Integrative Analysis of Rheumatoid Arthritis and Multiple Sclerosis for Identification of Putative Therapeutic Targets by Using Microarray and RNA-Sequencing

Abstract

Autoimmune diseases are considered as the leading cause of death through out the world. Multiple sclerosis (MS) and rheumatoid arthritis (RA) are the crucial life-threatening autoimmune disorders in which immune system reacts over actively. Because of disability to react to the inflammations and infections, immune system switches off response of the immune system to those infections. To provide a novel insight into the transformation of immune related disorders like multiple sclerosis and rheumatoid arthritis, microarray and RNA-Seq differential gene expression analysis has performed to examine expressions of genes simultaneously. About 10 datasets of multiple sclerosis and rheumatoid arthritis have been selected from ArrayExpress and European nucleotide archive (ENA). Quality control and normalization methods are applied with differential gene expression analysis by the selection of certain criteria that based on p−value and log2FC. Comparative analysis is performed in order to find common genes between rheumatoid arthritis (RA) and multiple sclerosis (MS). Pathway analysis proved the evidence about involvement of differentially expressed genes in cancer pathway. Simulations and sensitivity analysis has been performed by systems biology approach in order to find the most significant differentially ex pressed genes. Evading apoptosis and sustained angiogenesis are considered as the effective processes by the over expression of MsT1, S6K, Cox-2 and VEGF. MsT1 and S6K are recognized as the most sensitive genes in case of apoptosis that may play a particular role in immune related disorders. Similarly, Cox-2 and VEGF are inflam matory cytokines and identified as the most sensitive entities that may play role as potential diagnostic or prognostic biomarkers. Due to over-expression of MsT1, S6K, Cox-2 and VEGF, immunodeficiency causes that participates in the pathogenesis of autoimmune disorders including rheumatoid arthritis and multiple sclerosis.