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利用基因共表达网络方法在阿尔茨海默病不同阶段进行基因生物标志物发现。

Gene biomarker discovery at different stages of Alzheimer using gene co-expression network approach.

机构信息

Faculty of Electrical and Computer Engineering, University of Tabriz, Tabriz, Iran.

Department of Computer Engineering, Gowgan Educational Center, Tabriz Branch, Islamic Azad University, Tabriz, Iran.

出版信息

Sci Rep. 2020 Jul 22;10(1):12210. doi: 10.1038/s41598-020-69249-8.

Abstract

Alzheimer's disease (AD) is a chronic neurodegenerative disorder. It is the most common type of dementia that has remained as an incurable disease in the world, which destroys the brain cells irreversibly. In this study, a systems biology approach was adopted to discover novel micro-RNA and gene-based biomarkers of the diagnosis of Alzheimer's disease. The gene expression data from three AD stages (Normal, Mild Cognitive Impairment, and Alzheimer) were used to reconstruct co-expression networks. After preprocessing and normalization, Weighted Gene Co-Expression Network Analysis (WGCNA) was used on a total of 329 samples, including 145 samples of Alzheimer stage, 80 samples of Mild Cognitive Impairment (MCI) stage, and 104 samples of the Normal stage. Next, three gene-miRNA bipartite networks were reconstructed by comparing the changes in module groups. Then, the functional enrichment analyses of extracted genes of three bipartite networks and miRNAs were done, respectively. Finally, a detailed analysis of the authentic studies was performed to discuss the obtained biomarkers. The outcomes addressed proposed novel genes, including MBOAT1, ARMC7, RABL2B, HNRNPUL1, LAMTOR1, PLAGL2, CREBRF, LCOR, and MRI1and novel miRNAs comprising miR-615-3p, miR-4722-5p, miR-4768-3p, miR-1827, miR-940 and miR-30b-3p which were related to AD. These biomarkers were proposed to be related to AD for the first time and should be examined in future clinical studies.

摘要

阿尔茨海默病(AD)是一种慢性神经退行性疾病。它是世界上最常见的痴呆症类型,是一种无法治愈的疾病,会不可逆转地破坏脑细胞。在这项研究中,采用系统生物学方法发现了阿尔茨海默病诊断的新型 micro-RNA 和基因标志物。使用来自三个 AD 阶段(正常、轻度认知障碍和阿尔茨海默病)的基因表达数据来重建共表达网络。在预处理和归一化后,总共对 329 个样本(包括 145 个阿尔茨海默病阶段样本、80 个轻度认知障碍(MCI)阶段样本和 104 个正常阶段样本)使用加权基因共表达网络分析(WGCNA)。接下来,通过比较模块组的变化,重建了三个基因-miRNA 二分网络。然后,分别对三个二分网络的提取基因和 miRNAs 进行功能富集分析。最后,对获得的生物标志物进行了详细的真实研究分析。研究结果提出了新的基因,包括 MBOAT1、ARMC7、RABL2B、HNRNPUL1、LAMTOR1、PLAGL2、CREBRF、LCOR 和 MRI1,以及新的 miRNAs,包括 miR-615-3p、miR-4722-5p、miR-4768-3p、miR-1827、miR-940 和 miR-30b-3p,这些基因与 AD 有关。这些生物标志物首次被提出与 AD 有关,应该在未来的临床研究中进行检验。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88af/7376049/1e0e3afd29ed/41598_2020_69249_Fig1_HTML.jpg

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