1st International and 10th National Iranian Conference on Bioinformatics
RNA-sequencing of CD4+ T cells in Relapsing-Remitting Multiple Sclerosis patients at relapse; deciphering the involvement of novel genes and pathways
Paper ID : 1469-ICB10
Authors:
Zahra Salehi *1, Saeed Talebi2, Samaneh Maleknia3, Fahimeh Palizban4, Abdorreza Naser Moghadasi5, Kaveh Kavousi4, Mohammad Ali Sahraian5, Maryam Izad1
1Immunology Department, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
2Department of Medical Genetics and Molecular Biology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.
3Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
4Laboratory of Complex Biological Systems and Bioinformatics (CBB), Department of Bioinformatics, Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran.
5MS Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.
Abstract:
CD4+ T cells known as a noteworthy potential modulator of inflammation in multiple sclerosis (MS). In the current study, we investigated the transcriptome profile of CD4+ T cells in relapsing-remitting MS (RRMS) patients at relapse phase. We performed RNA sequencing of CD4+ T cells isolated from RRMS patients at relapse phase and age- and sex-matched healthy controls. The edgeR statistical method was employed to determine differential expression genes (DEGs). The gene set enrichment analysis was subsequently performed. Applying physical interaction network, genes with higher degrees were selected as hub genes.
A total of 1278 genes and 1034 gens were defined at significantly higher or lower levels, respectively, in CD4+ T cells of RRMS patients at relapse phase as compared with healthy controls. The top up- and down-regulated gene were JAML and KDM3A. The detected DEGs were remarkably on chromosomes 1 and 2, respectively. The DEGs were mainly enriched in pathways such as ‘regulation of transcription, DNA-templated’, ‘regulation of B cell receptor signaling pathway’, ‘protein phosphorylation’, ‘epidermal growth factor receptor signaling pathway’, and ‘positive regulation of neurogenesis’. Moreover, 16 KEGG pathways mostly associated with the immune system and viral infections were enriched. In the constructed physical interaction networks, UBA52 and TP53 were illustrated as the most highly ranked hub genes among up- and down-regulated genes, correspondingly.
Conclusions: By applying global transcriptome profiling of CD4+ T cells, we deciphers the involvement of several novel genes and pathways in MS pathogenesis. The present results need to be affirmed by in vivo and in vitro studies.
Keywords:
RRMS; CD4+ T cells; RNA-sequencing; Transcriptome; Functional modules; Chromosomal enrichment
Status : Paper Accepted (Oral Presentation)