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通过结合单细胞数据分析和机器学习算法的生物信息学方法鉴定阿尔茨海默病和新冠肺炎的生物标志物。

Identification of biomarkers in Alzheimer's disease and COVID-19 by bioinformatics combining single-cell data analysis and machine learning algorithms.

作者信息

Li Juntu, Tao Linfeng, Zhou Yanyou, Zhu Yue, Li Chao, Pan Yiyuan, Yao Ping, Qian Xuefeng, Liu Jun

机构信息

Department of Critical Care Medicine and Emergency, The Affiliated Suzhou Hospital of Nanjing Medical University (Suzhou Municipal Hospital), Gusu School, Nanjing Medical University, Suzhou Clinical Medical Center of Critical Care Medicine, Suzhou, Jiangsu, China.

Department of Breast and Thyroid Surgery, The Affiliated Suzhou Hospital of Nanjing Medical University (Suzhou Municipal Hospital), Gusu School, Nanjing Medical University, Suzhou, Jiangsu, China.

出版信息

PLoS One. 2025 Feb 18;20(2):e0317915. doi: 10.1371/journal.pone.0317915. eCollection 2025.

Abstract

BACKGROUND

Since its emergence in 2019, COVID-19 has become a global epidemic. Several studies have suggested a link between Alzheimer's disease (AD) and COVID-19. However, there is little research into the mechanisms underlying these phenomena. Therefore, we conducted this study to identify key genes in COVID-19 associated with AD, and evaluate their correlation with immune cells characteristics and metabolic pathways.

METHODS

Transcriptome analyses were used to identify common biomolecular markers of AD and COVID-19. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were performed on gene chip datasets (GSE213313, GSE5281, and GSE63060) from AD and COVID-19 patients to identify genes associated with both conditions. Gene ontology (GO) enrichment analysis identified common molecular mechanisms. The core genes were identified using machine learning. Subsequently, we evaluated the relationship between these core genes and immune cells and metabolic pathways. Finally, our findings were validated through single-cell analysis.

RESULTS

The study identified 484 common differentially expressed genes (DEGs) by taking the intersection of genes between AD and COVID-19. The black module, containing 132 genes, showed the highest association between the two diseases according to WGCNA. GO enrichment analysis revealed that these genes mainly affect inflammation, cytokines, immune-related functions, and signaling pathways related to metal ions. Additionally, a machine learning approach identified eight core genes. We identified links between these genes and immune cells and also found a association between EIF3H and oxidative phosphorylation.

CONCLUSION

This study identifies shared genes, pathways, immune alterations, and metabolic changes potentially contributing to the pathogenesis of both COVID-19 and AD.

摘要

背景

自2019年出现以来,新冠病毒病(COVID-19)已成为全球大流行疾病。多项研究表明阿尔茨海默病(AD)与COVID-19之间存在联系。然而,对于这些现象背后的机制研究甚少。因此,我们开展了本研究,以确定与AD相关的COVID-19关键基因,并评估它们与免疫细胞特征和代谢途径的相关性。

方法

采用转录组分析来确定AD和COVID-19的共同生物分子标志物。对来自AD和COVID-19患者的基因芯片数据集(GSE213313、GSE5281和GSE63060)进行差异表达分析和加权基因共表达网络分析(WGCNA),以确定与这两种疾病相关的基因。基因本体(GO)富集分析确定了共同的分子机制。使用机器学习确定核心基因。随后,我们评估了这些核心基因与免疫细胞和代谢途径之间的关系。最后,通过单细胞分析验证了我们的研究结果。

结果

通过取AD和COVID-19之间的基因交集,本研究确定了484个共同的差异表达基因(DEG)。根据WGCNA,包含132个基因的黑色模块显示出这两种疾病之间的最高关联性。GO富集分析表明,这些基因主要影响炎症、细胞因子、免疫相关功能以及与金属离子相关的信号通路。此外,一种机器学习方法确定了8个核心基因。我们确定了这些基因与免疫细胞之间的联系,还发现EIF3H与氧化磷酸化之间存在关联。

结论

本研究确定了可能导致COVID-19和AD发病机制的共享基因、途径、免疫改变和代谢变化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c7e/11835241/dcf30887a7de/pone.0317915.g001.jpg

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