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利用微阵列分析鉴定创伤后应激障碍中的关键基因和通路

Identification of Key Genes and Pathways in Post-traumatic Stress Disorder Using Microarray Analysis.

作者信息

Bian Yaoyao, Yang Lili, Zhao Min, Li Zhengjun, Xu Yuying, Zhou Guilian, Li Wenlin, Zeng Li

机构信息

School of Nursing, Nanjing University of Chinese Medicine, Nanjing, China.

School of First Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, China.

出版信息

Front Psychol. 2019 Feb 27;10:302. doi: 10.3389/fpsyg.2019.00302. eCollection 2019.

Abstract

Post-traumatic stress disorder (PTSD) is characterized by impaired fear extinction, excessive anxiety, and depression. However, the potential pathogenesis and cause of PTSD are not fully understood. Hence, the purpose of this study was to identify key genes and pathway involved in PTSD and reveal underlying molecular mechanisms by using bioinformatics analysis. The mRNA microarray expression profile dataset was retrieved and downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were screened using GEO2R. Gene ontology (GO) was used for gene function annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway was performed for enrichment analysis. Subsequently, protein-protein interaction (PPI) network and module analysis by the plugin MCODE were mapped by Cytoscape software. Finally, these key genes were verified in stress-exposed models by Real-Time quantitative (qRT-PCR). In addition, we performed text mining among the key genes and pathway with PTSD by using COREMINE. A total of 1004 DEGs were identified. Gene functional annotations and enrichment analysis indicated that the most associated pathway was closely related to the Wnt signaling pathway. Using PPI network and module analysis, we identified a group of "seed" genes. These genes were further verified by qRT-PCR. In addition, text mining indicated that the altered CYP1A2, SYT1, and NLGN1 affecting PTSD might work via the Wnt signaling pathway. By using bioinformatics analysis, we identified a number of genes and relevant pathway which may represent key mechanisms associated with PTSD. However, these findings require verification in future experimental studies.

摘要

创伤后应激障碍(PTSD)的特征是恐惧消退受损、过度焦虑和抑郁。然而,PTSD的潜在发病机制和病因尚未完全明确。因此,本研究旨在通过生物信息学分析确定参与PTSD的关键基因和通路,并揭示其潜在的分子机制。从基因表达综合数据库(GEO)中检索并下载了mRNA微阵列表达谱数据集。使用GEO2R筛选差异表达基因(DEG)。利用基因本体论(GO)进行基因功能注释,并进行京都基因与基因组百科全书(KEGG)通路富集分析。随后,通过Cytoscape软件绘制蛋白质-蛋白质相互作用(PPI)网络,并使用插件MCODE进行模块分析。最后,通过实时定量(qRT-PCR)在应激暴露模型中验证这些关键基因。此外,我们使用COREMINE对PTSD的关键基因和通路进行文本挖掘。共鉴定出1004个DEG。基因功能注释和富集分析表明,最相关的通路与Wnt信号通路密切相关。通过PPI网络和模块分析,我们鉴定出一组“种子”基因。这些基因通过qRT-PCR进一步验证。此外,文本挖掘表明,影响PTSD的CYP1A2、SYT1和NLGN1的改变可能通过Wnt信号通路发挥作用。通过生物信息学分析,我们鉴定出一些基因和相关通路,它们可能代表与PTSD相关的关键机制。然而,这些发现需要在未来的实验研究中进行验证。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3325/6403462/213808edfaa4/fpsyg-10-00302-g001.jpg

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