Integrating the Ribonucleic Acid Sequencing Data From Various Studies for Exploring the Multiple Sclerosis-Related Long Noncoding Ribonucleic Acids and Their Functions

Front Genet. 2019 Nov 12;10:1136. doi: 10.3389/fgene.2019.01136. eCollection 2019.


Multiple sclerosis (MS) is a chronic fatal central nervous system (CNS) disease involving in complex immunity dysfunction. Recently, long noncoding RNAs (lncRNAs) were discovered as the important regulatory factors for the pathogenesis of MS. However, these findings often cannot be repeated and confirmed by the subsequent studies. We considered that the small-scale samples or the heterogeneity among various tissues may result in the divergence of the results. Currently, RNA-seq has become a powerful approach to quantify the abundances of lncRNA transcripts. Therefore, we comprehensively collected the MS-related RNA-seq data from a variety of previous studies, and integrated these data using an expression-based meta-analysis to identify the differentially expressed lncRNA between MS patients and controls in whole samples and subgroups. Then, we performed the Jensen-Shannon (JS) divergence and cluster analysis to explore the heterogeneity and expression specificity among various tissues. Finally, we investigated the potential function of identified lncRNAs for MS using weighted gene co-expression network analysis (WGCNA) and gene set enrichment analysis (GSEA), and 5,420 MS-related lncRNAs specifically expressed in the brain tissue were identified. The subgroup analysis found a small heterogeneity of the lncRNA expression profiles between brain and blood tissues. The results of WGCNA and GSEA showed that a potential important function of lncRNAs in MS may be involved in the regulation of ribonucleoproteins and tumor necrosis factor cytokines receptors. In summary, this study provided a strategy to explore disease-related lncRNAs on genome-wide scale, and our findings will be benefit to improve the understanding of MS pathogenesis.

Keywords: function analysis; long non-coding ribonucleic acids; meta-analysis; multiple sclerosis; ribonucleic acid sequencing.