多发性硬化症和肌萎缩侧索硬化症间潜在关键基因及生物学途径

关键词：多发性硬化症  肌萎缩侧索硬化症  生物信息学  差异表达基因

Keywords:multiple sclerosis  amyotrophic lateral sclerosis  bioinformatics  differentially expressed genes

摘要：

      摘要 目的：联合多种生物信息学分析方法筛选多发性硬化症（multiple sclerosis， MS）与肌萎缩侧索硬化症（amyotrophic lateral sclerosis， ALS）之间的枢纽基因，从遗传学角度探索以上两种疾病的潜在联系并辅以诊断、治疗。 方法：利用GEO数据库筛选基因表达数据集，利用R软件中的Limma包筛选差异表达基因（differentially expressed genes， DEGs），对差异基因进行GO术语分析、KEGG通路分析、蛋白相互作用网络分析（protein-protein interaction， PPI）、ROC分析以及qRT-PCR分析等。 结果：共纳入2个GEO数据集（GSE108000和GSE68605），与正常组相比，MS存在681个DEGs，ALS存在1365个DEGs，MS与ALS之间存在66个共同DEGs，其中前10个枢纽基因被证明与MS和ALS存在密切联系。此外，为更好的辅以临床诊断与治疗，本研究使用Enrichr平台检测前10个枢纽基因的标志性药物分子。同时根据ROC分析，以及qRT-PCR分析确定前四个枢纽基因的诊断效能。 结论：通过生物信息学方法有效地筛选出MS和ALS间的枢纽基因，为开发临床诊断与治疗靶点提供新思路。

Abstract:

      Abstract Objective： Combining multiple bioinformatics analyses to screen for hub genes between multiple sclerosis （MS） and amyotrophic lateral sclerosis （ALS） and to explore the potential relationship between the two diseases from a genetic perspective. Method： Gene expression datasets were downloaded from the GEO database， differentially expressed genes （DEGs） were screened using the Limma package in the R software， and GO terminology analysis， KEGG pathway analysis， protein-protein interaction （PPI）， ROC analysis， and qRT-PCR analysis were performed on the differentially expressed genes. Result： A total of 2 GEO datasets （GSE108000 and GSE68605） were included，681 DEGs were present in MS and 1365 DEGs were available in ALS compared to the normal group， and 66 common DEGs were observed both in MS and ALS， among which the top 10 hub genes were identified to be significantly associated with MS and ALS. In addition，in order to better supplement clinical diagnosis and treatment， the Enrichr platform was used to detect signature drug molecules for the top 10 hub genes. The diagnostic efficacy of the first four hub genes was also determined based on ROC analysis as well as qRT-PCR analysis. Conclusion： A bioinformatics approach was applied to effectively screen out the hub genes between MS and ALS， which provided new thoughts for the clinical diagnostic and therapeutic target development.