基于加权基因共表达网络分析识别强迫症的基因表达模块和枢纽基因
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厦门市仙岳医院课题 (2020XYYB05)


Co-expression modules based on WGCNA and key genes related to obsessive-compulsive disorder
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    摘要:

    目的 使用加权基因共表达网络分析(WGCNA)识别强迫症的共表达模块和枢纽基因。 方法 从基因表达数据库(GEO)下载 GSE60190 数据集,对 15 例强迫症患者和 14 名健康对照者的尸脑 背外侧前额叶皮质(DLPFC)基因表达数据进行分析。通过 WGCNA 确定与强迫症相关的共表达模块, 采用 Metascape 数据库对与强迫症相关的关键模块进行 GO 富集分析,采用 STRING 数据库构建关键模 块的蛋白质 - 蛋白质相互作用(PPI)网络,采用 Cytoscape 软件识别模块内的枢纽基因。结果 共识别 9 个强迫症基因共表达模块,模块特征基因值为 168~2 676。绿色模块(MEgreen)与强迫症呈正相关 (r=0.52,P校正=0.036)。富集分析结果显示,MEgreen 涉及多个生物过程,包括对类固醇激素的反应、对电 离辐射的反应、活性氧生物合成过程的调节、横纹肌细胞分化的调节、ATP 酶活性的调节、“从头”蛋白 质折叠、蛋白质导入和微管细胞骨架组织等。PSMD12、PSMD1、CDKN1B、CDC34,SRSF1和CCT2基因 为与强迫症相关的枢纽基因。结论 MEgreen 和PSMD12、PSMD1、CDKN1B、CDC34、SRSF1及CCT2共 6 个基因,可能通过泛素系统、细胞周期、应激反应和类固醇激素反应等方面在强迫症发生和发展中发 挥一定作用。

    Abstract:

    Objective To identify the gene co-expression modules and hub genes of obsessivecompulsive disorder (OCD) through weighted gene co-expression network analysis (WGCNA) of gene expression profiles. Methods The GSE60190 dataset was downloaded from the Gene Expression Database (GEO). The gene expression data from the dorsolateral prefrontal cortex (DLPFC) of postmortem brain of 15 OCD patients and 14 healthy controls were used to detected the co-expression module related to OCD. The co-expression modules related to OCD were identified by WGCNA. GO enrichment analysis was performed on key modules related to OCD by Metascape database. Protein-protein interaction (PPI) networks for key modules were constructed through STRING database. CytoHubba in Cytoscape was used to identify hub gene candidates. Results A total of 9 co-expression modules of OCD genes were identified, with module characteristic gene values ranging from 168 to 2 676. The green module (MEgreen) was positively correlated with OCD (r=0.52, Pcorrected=0.036). The enrichment analysis results showed that MEgreen involves multiple biological processes (BPs), including response to steroid hormones, response to ionizing radiation, regulation of reactive oxygen species biosynthesis process, regulation of striated muscle cell differentiation, regulation of ATPase activity, "de novo" protein folding, protein import, and microtubule cytoskeletal organization. PSMD12, PSMD1, CDKN1B, CDC34,SRSF1, and CCT2 were identified as hub genes that might be associated with the development of OCD. Conclusions MEgreen and six genes, including PSMD12, PSMD1, CDKN1B, CDC34, SRSF1, and CCT2, may play a certain role in the occurrence and development of obsessive-compulsive disorder through ubiquitin system, cell cycle, stress response, and steroid hormone response.

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吴娓娓,王建军,张振清,丁丽君.基于加权基因共表达网络分析识别强迫症的基因表达模块和枢纽基因[J].神经疾病与精神卫生,2023,23(8):
DOI :10.3969/j. issn.1009-6574.2023.08.004.

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  • 在线发布日期: 2023-08-29