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基于加权基因共表达网络分析鉴定 COVID-19 相关卒中的潜在生物学过程和关键基因

Weighted Gene Co-Expression Network Analysis to Identify Potential Biological Processes and Key Genes in COVID-19-Related Stroke.

机构信息

Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, 530021 Guangxi, China.

出版信息

Oxid Med Cell Longev. 2022 May 9;2022:4526022. doi: 10.1155/2022/4526022. eCollection 2022.

DOI:10.1155/2022/4526022
PMID:35557984
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9088964/
Abstract

The purpose of this research was to explore the underlying biological processes causing coronavirus disease 2019- (COVID-19-) related stroke. The Gene Expression Omnibus (GEO) database was utilized to obtain four COVID-19 datasets and two stroke datasets. Thereafter, we identified key modules via weighted gene co-expression network analysis, following which COVID-19- and stroke-related crucial modules were crossed to identify the common genes of COVID-19-related stroke. The common genes were intersected with the stroke-related hub genes screened via Cytoscape software to discover the critical genes associated with COVID-19-related stroke. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis for common genes associated with COVID-19-related stroke, and the Reactome database was used to annotate and visualize the pathways involved in the key genes. Two COVID-19-related crucial modules and one stroke-related crucial module were identified. Subsequently, the top five genes were screened as hub genes after visualizing the genes of stroke-related critical module using Cytoscape. By intersecting the COVID-19- and stroke-related crucial modules, 28 common genes for COVID-19-related stroke were identified. ITGA2B and ITGB3 have been further identified as crucial genes of COVID-19-related stroke. Functional enrichment analysis indicated that both ITGA2B and ITGB3 were involved in integrin signaling and the response to elevated platelet cytosolic Ca, thus regulating platelet activation, extracellular matrix- (ECM-) receptor interaction, the PI3K-Akt signaling pathway, and hematopoietic cell lineage. Therefore, platelet activation, ECM-receptor interaction, PI3K-Akt signaling pathway, and hematopoietic cell lineage may represent the potential biological processes associated with COVID-19-related stroke, and ITGA2B and ITGB3 may be potential intervention targets for COVID-19-related stroke.

摘要

本研究旨在探讨导致 2019 冠状病毒病（COVID-19）相关脑卒中的潜在生物学过程。利用基因表达综合数据库（GEO）获取了四个 COVID-19 数据集和两个脑卒中数据集。然后，我们通过加权基因共表达网络分析鉴定关键模块，之后将 COVID-19 和脑卒中相关关键模块进行交叉，以鉴定 COVID-19 相关脑卒中的共同基因。通过 Cytoscape 软件将共同基因与脑卒中相关枢纽基因进行交叉，发现与 COVID-19 相关脑卒中相关的关键基因。对与 COVID-19 相关脑卒中的共同基因进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）富集分析，并使用 Reactome 数据库对关键基因涉及的通路进行注释和可视化。鉴定出两个 COVID-19 相关关键模块和一个脑卒中相关关键模块。随后，使用 Cytoscape 可视化脑卒中相关关键模块的基因后，筛选出前五名基因作为枢纽基因。通过 COVID-19 和脑卒中相关关键模块的交叉，鉴定出 28 个与 COVID-19 相关脑卒中的共同基因。进一步鉴定出 ITGA2B 和 ITGB3 是 COVID-19 相关脑卒中的关键基因。功能富集分析表明，ITGA2B 和 ITGB3 均参与整合素信号转导和血小板胞浆 Ca 升高反应，从而调节血小板活化、细胞外基质（ECM）-受体相互作用、PI3K-Akt 信号通路和造血细胞谱系。因此，血小板活化、ECM-受体相互作用、PI3K-Akt 信号通路和造血细胞谱系可能代表与 COVID-19 相关脑卒中相关的潜在生物学过程，ITGA2B 和 ITGB3 可能是 COVID-19 相关脑卒中的潜在干预靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92db/9088964/89aa143bce35/OMCL2022-4526022.007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92db/9088964/89aa143bce35/OMCL2022-4526022.007.jpg

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