Bioinformatics and systematic biology methods to determine the pathogenic link between COVID-19 and atrial fibrillation

Abstract

Abstract The coronavirus disease 2019 (COVID-19) epidemic has not been effectively controlled thus far. Atrial fibrillation (AF) is a risk factor for COVID-19, and if not controlled in a timely manner, it will cause a catastrophic situation. However, the molecular mechanism of AF and COVID-19 is not well understood. We performed transcriptome analysis to capture common signaling pathways and molecular markers of AF and COVID-19, which will help in understanding the link between COVID-19 and AF. Three AF datasets (GSE41177, GSE31821, GSE79768) and one COVID-19 dataset (GSE147507) from the Gene Expression Omnibus (GEO) database were used in this study. Differential expression analysis of the datasets identified differential genes common to both diseases. To explore the biological mechanisms of the differential genes, gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG), protein-protein interaction (PPI), receiver operating characteristic curve (ROC), miRNA- transcriptionfactor (TF)-mRNA network, drug candidate prediction, molecular docking, and gene-disease association analyses were performed. We finally found 63 DEGs common to COVID-19 and AF. GO/KEGG allowed the common biological functions and signaling pathways of both diseases to be understood. Based on the PPI network, 5 hub genes (FCGR3B, IL1B, CXCR4, CSF2RB, and SELL) were identified, with CXCR4 as the most diagnostic and therapeutic target gene. Based on CXCR4, a miRNA-TF-mRNA network was constructed. Five potential therapeutic agents closely related to CXCR4 were identified, and their reliability was verified by molecular docking. Finally, possible associated diseases were analyzed. Taken together, our findings will help scholars understand the potential biological mechanisms between COVID-19 and AF. The development of precise therapeutic agents targeting CXCR4 is of great significance for COVID-19 patients with a history of AF.