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整合来自各种研究的核糖核酸测序数据,以探索与多发性硬化症相关的长链非编码核糖核酸及其功能。

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

作者信息

Han Zhijie, Hua Jiao, Xue Weiwei, Zhu Feng

机构信息

College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.

School of Pharmaceutical Sciences, Chongqing University, Chongqing, China.

出版信息

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

Abstract

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.

摘要

多发性硬化症(MS)是一种慢性致命性中枢神经系统(CNS)疾病,涉及复杂的免疫功能障碍。最近,长链非编码RNA(lncRNAs)被发现是MS发病机制的重要调节因子。然而,这些发现往往无法被后续研究重复和证实。我们认为,样本规模较小或不同组织之间的异质性可能导致结果出现差异。目前,RNA测序已成为一种强大的方法来量化lncRNA转录本的丰度。因此,我们全面收集了以往各种研究中与MS相关的RNA测序数据,并使用基于表达的荟萃分析整合这些数据,以识别MS患者与对照组在全样本和亚组中差异表达的lncRNA。然后,我们进行了 Jensen-Shannon(JS)散度和聚类分析,以探索不同组织之间的异质性和表达特异性。最后,我们使用加权基因共表达网络分析(WGCNA)和基因集富集分析(GSEA)研究了已识别的lncRNA对MS的潜在功能,并且鉴定出了5420个在脑组织中特异性表达的与MS相关的lncRNA。亚组分析发现脑和血组织之间lncRNA表达谱存在微小异质性。WGCNA和GSEA的结果表明,lncRNA在MS中的一个潜在重要功能可能涉及核糖核蛋白和肿瘤坏死因子细胞因子受体的调节。总之,本研究提供了一种在全基因组范围内探索疾病相关lncRNA的策略,我们的发现将有助于增进对MS发病机制的理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c50/6861379/8399f27b7ee4/fgene-10-01136-g001.jpg

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