Identification of critical genes and molecular pathways in COVID-19 myocarditis and constructing gene regulatory networks by bioinformatic analysis

Abstract

Background There is growing evidence of a strong relationship between COVID-19 and myocarditis. However, there are few bioinformatics-based analyses of critical genes and the mechanisms related to COVID-19 Myocarditis. This study aimed to identify critical genes related to COVID-19 Myocarditis by bioinformatic methods, explore the biological mechanisms and gene regulatory networks, and probe related drugs. Methods The gene expression data of GSE150392 and GSE167028 were obtained from the Gene Expression Omnibus (GEO), including cardiomyocytes derived from human induced pluripotent stem cells infected with SARS-CoV-2 in vitro and GSE150392 from patients with myocarditis infected with SARS-CoV-2 and the GSE167028 gene expression dataset. Differentially expressed genes (DEGs) (adjusted P-Value <0.01 and |Log2 Fold Change| ≥2) in GSE150392 were assessed by NetworkAnalyst 3.0. Meanwhile, significant modular genes in GSE167028 were identified by weighted gene correlation network analysis (WGCNA) and overlapped with DEGs to obtain common genes. Functional enrichment analyses were performed by using the "clusterProfiler" package in the R software, and protein-protein interaction (PPI) networks were constructed on the STRING website (https://cn.string-db.org/). Critical genes were identified by the CytoHubba plugin of Cytoscape by 5 algorithms. Transcription factor-gene (TF-gene) and Transcription factor-microRibonucleic acid (TF-miRNA) coregulatory networks construction were performed by NetworkAnalyst 3.0 and displayed in Cytoscape. Finally, Drug Signatures Database (DSigDB) was used to probe drugs associated with COVID-19 Myocarditis. Results Totally 850 DEGs (including 449 up-regulated and 401 down-regulated genes) and 159 significant genes in turquoise modules were identified from GSE150392 and GSE167028, respectively. Functional enrichment analysis indicated that common genes were mainly enriched in biological processes such as cell cycle and ubiquitin-protein hydrolysis. 6 genes (CDK1, KIF20A, PBK, KIF2C, CDC20, UBE2C) were identified as critical genes. TF-gene interactions and TF-miRNA coregulatory network were constructed successfully. A total of 10 drugs, (such as Etoposide, Methotrexate, Troglitazone, etc) were considered as target drugs for COVID-19 Myocarditis. Conclusions Through bioinformatics method analysis, this study provides a new perspective to explore the pathogenesis, gene regulatory networks and provide drug compounds as a reference for COVID-19 Myocarditis. It is worth highlighting that critical genes (CDK1, KIF20A, PBK, KIF2C, CDC20, UBE2C) may be potential biomarkers and treatment targets of COVID-19 Myocarditis for future study.

Apoptosis Response in Acute Lymphoblastic Leukemia Cells after Methotrexate Treatment-A Systematic Review

“…Exploring the genetic implications, several studies conducted between 2008 and 2022 outlined the influence of MTX on genes such as TYMS, CTP, BCL-3, CDC20, CENPF, FAIM3, POLD3, RPA3, and RNASEH2A. The mechanisms ranged from inhibiting crucial enzymes in the folate pathway, affecting nucleotide metabolism, and causing chromosomal instability, to interfering with DNA repair and synthesis processes (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26).…”

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