Weighted Gene Co‐Expression Network Analysis to Identify Potential Biological Processes and Key Genes in COVID‐19‐Related Stroke
Gengyu Cen, Liuyu Liu, Jun Wang, Xue Wang, Shijian Chen, Yiting Song, Zhijian Liang
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 2+ , 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.