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揭示基因组网络中阿尔茨海默病、血管性痴呆和帕金森病的模块相似性和差异性。

Revealing the Modular Similarities and Differences Among Alzheimer's Disease, Vascular Dementia, and Parkinson's Disease in Genomic Networks.

机构信息

School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.

Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China.

出版信息

Neuromolecular Med. 2022 Jun;24(2):125-138. doi: 10.1007/s12017-021-08670-2. Epub 2021 Jun 12.

Abstract

Alzheimer's disease (AD), vascular dementia (VD), and Parkinson's disease (PD) exert increasingly lethal or disabling effects on humans, but the associations among these diseases at the molecular level remain unclear. In our research, lists of genes related to these three diseases were acquired from public databases. We constructed gene-gene networks of the lists of disease-related genes using the STRING database and selected the plug-in MCODE as the most suitable method to divide the three disease-associated networks into modules through an entropy calculation. Notably, 1173 AD-related, 203 VD-related, and 722 PD-related genes as well as 72 overlapping genes were observed among the three diseases. By dividing the modules from the gene network, we divided the AD-related gene network into 27 modules, the VD-related gene network into 8 modules, and the PD-related gene network into 17 modules. After the enrichment analysis of each disease-related gene, 146 overlapping biological processes and 32 overlapping pathways were identified. Ultimately, through similarity analysis of the genes, biological processes, and pathways, we found that AD and VD were the most closely related at the biological process and pathway levels, with similarity coefficients of 0.2784 and 0.3626, respectively. After analyzing the overlapping gene network, we found that INS might play an important role in the network and that insulin and its signaling pathways may play a key role in these neurodegenerative diseases. Our research illustrates a new method for in-depth research on the three diseases, which may accelerate the progress of developing new therapeutics and may be applied to prevent neurodegenerative diseases.

摘要

阿尔茨海默病(AD)、血管性痴呆(VD)和帕金森病(PD)对人类的致死或致残影响日益严重,但这些疾病在分子水平上的关联尚不清楚。在我们的研究中,从公共数据库中获取了与这三种疾病相关的基因列表。我们使用 STRING 数据库构建了疾病相关基因列表的基因-基因网络,并选择插件 MCODE 作为最适合的方法,通过熵计算将三个疾病相关网络划分为模块。值得注意的是,在这三种疾病中观察到了 1173 个 AD 相关、203 个 VD 相关和 722 个 PD 相关基因以及 72 个重叠基因。通过对基因网络中的模块进行划分,我们将 AD 相关基因网络分为 27 个模块,VD 相关基因网络分为 8 个模块,PD 相关基因网络分为 17 个模块。对每个疾病相关基因进行富集分析后,鉴定出 146 个重叠的生物学过程和 32 个重叠的途径。最终,通过基因、生物学过程和途径的相似性分析,我们发现 AD 和 VD 在生物学过程和途径水平上的相关性最强,相似系数分别为 0.2784 和 0.3626。在分析重叠基因网络后,我们发现 INS 可能在网络中发挥重要作用,胰岛素及其信号通路可能在这些神经退行性疾病中发挥关键作用。我们的研究为深入研究这三种疾病提供了一种新方法,这可能加速开发新疗法的进展,并可能应用于预防神经退行性疾病。

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