Liu Yang, Gu Hui-Yun, Zhu Jie, Niu Yu-Ming, Zhang Chao, Guo Guang-Ling
Center for Evidence-Based Medicine and Clinical Research, Taihe Hospital, Hubei University of Medicine, Shiyan, China.
Department of Orthopedic, Zhongnan Hospital of Wuhan University, Wuhan, China.
Front Physiol. 2019 Aug 20;10:1081. doi: 10.3389/fphys.2019.01081. eCollection 2019.
Bipolar disorder (BD) is a complex mental disorder with high mortality and disability rates worldwide; however, research on its pathogenesis and diagnostic methods remains limited. This study aimed to elucidate potential candidate hub genes and key pathways related to BD in a pre-frontal cortex sample. Raw gene expression profile files of GSE53987, including 36 samples, were obtained from the gene expression omnibus (GEO) database. After data pre-processing, 10,094 genes were selected for weighted gene co-expression network analysis (WGCNA). After dividing highly related genes into 19 modules, we found that the pink, midnight blue, and brown modules were highly correlated with BD. Functional annotation and pathway enrichment analysis for modules, which indicated some key pathways, were conducted based on the Enrichr database. One of the most remarkable significant pathways is the Hippo signaling pathway and its positive transcriptional regulation. Finally, 30 hub genes were identified in three modules. Hub genes with a high degree of connectivity in the PPI network are significantly enriched in positive regulation of transcription. In addition, the hub genes were validated based on another dataset (GSE12649). Taken together, the identification of these 30 hub genes and enrichment pathways might have important clinical implications for BD treatment and diagnosis.
双相情感障碍（BD）是一种复杂的精神障碍，在全球范围内具有较高的死亡率和致残率；然而，关于其发病机制和诊断方法的研究仍然有限。本研究旨在阐明前额叶皮质样本中与双相情感障碍相关的潜在候选枢纽基因和关键通路。从基因表达综合数据库（GEO）中获取了GSE53987的原始基因表达谱文件，其中包括36个样本。经过数据预处理后，选择了10,094个基因进行加权基因共表达网络分析（WGCNA）。在将高度相关的基因划分为19个模块后，我们发现粉色、午夜蓝和棕色模块与双相情感障碍高度相关。基于Enrichr数据库对模块进行功能注释和通路富集分析，结果表明了一些关键通路。其中最显著的重要通路之一是Hippo信号通路及其正向转录调控。最后，在三个模块中鉴定出30个枢纽基因。在蛋白质-蛋白质相互作用（PPI）网络中具有高度连接性的枢纽基因在转录的正向调控中显著富集。此外，基于另一个数据集（GSE12649）对枢纽基因进行了验证。综上所述，这些30个枢纽基因和富集通路的鉴定可能对双相情感障碍的治疗和诊断具有重要的临床意义。
