Bioinformatics and system biology approach to identify the influences among COVID-19, ARDS and sepsis

Abstract

Background Severe coronavirus disease 2019 (COVID -19) has led to severe pneumonia or acute respiratory distress syndrome (ARDS) worldwide. we have noted that many critically ill patients with COVID-19 present with typical sepsis-related clinical manifestations, including multiple organ dysfunction syndrome, coagulopathy, and septic shock. The molecular mechanisms that underlie COVID-19, ARDS and sepsis are not well understood. The objectives of this study were to analyze potential molecular mechanisms and identify potential drugs for the treatment of COVID-19, ARDS and sepsis using bioinformatics and a systems biology approach. Methods Three RNA-seq datasets (GSE171110, GSE76293 and GSE137342) from Gene Expression Omnibus (GEO) were employed to detect mutual differentially expressed genes (DEGs) for the patients with the COVID-19, ARDS and sepsis for functional enrichment, pathway analysis, and candidate drugs analysis. Results We obtained 110 common DEGs among COVID-19, ARDS and sepsis. ARG1, FCGR1A, MPO, and TLR5 are the most influential hub genes. The infection and immune-related pathways and functions are the main pathways and molecular functions of these three diseases. FOXC1, YY1, GATA2, FOXL, STAT1 and STAT3 are important TFs for COVID-19. mir-335-5p, miR-335-5p and hsa-mir-26a-5p were associated with COVID-19. Finally, the hub genes retrieved from the DSigDB database indicate multiple drug molecules and drug-targets interaction. Conclusion We performed a functional analysis under ontology terms and pathway analysis and found some common associations among COVID-19, ARDS and sepsis. Transcription factors–genes interaction, protein–drug interactions, and DEGs-miRNAs coregulatory network with common DEGs were also identified on the datasets. We believe that the candidate drugs obtained in this study may contribute to the effective treatment of COVID-19.

Bioinformatics and system biology approach to identify potential common pathogenesis for COVID-19 infection and sarcopenia

“…TFs and miRNAs regulate gene expression in transcription and post-transcription, respectively, and the results suggest that the transcription factor FOXC1 and miRNA (hsa-mir-155-5p) may be common molecules that simultaneously regulate the expression of these hub genes. FOXC1 is an important member of the FOX family of transcription factors, and several studies have reported that it is an important TF for COVID-19 ( 81 , 82 ). And microRNA-155-5p is significantly upregulated in the acute phase of COVID-19, which promotes its immune-inflammatory response ( 83 , 84 ), thus establishing its association with disease prognosis and playing an important role as a useful biomarker for monitoring and diagnosing COVID-19 disease ( 85 ).…”

Tiny Guides, Big Impact: Focus on the Opportunities and Challenges of miR-Based Treatments for ARDS

“…In a study of miR-384-5p in LPS-induced ALI, information from TargetScan, miRanda, and miRBase was combined to determine the target of miR-384-5p, confirmed by luciferase assay [ 48 ]. Another study conducted by Li et al identified common differentially expressed genes among COVID-19, ARDS, and sepsis patients, followed by gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and enrichment analysis using DAVID [ 49 ]. Protein-protein interaction (PPI) networks were further constructed in STRING, which integrates known and predicted PPIs.…”

“…Protein-protein interaction (PPI) networks were further constructed in STRING, which integrates known and predicted PPIs. Cytohubba, a plugin in Cytoscape, was used to extract the hub gene in the PPI network to make further predictions [ 49 ]. Tarbase and mirTarbase determined potential regulatory miRs for differentially expressed genes [ 49 ].…”

“…Cytohubba, a plugin in Cytoscape, was used to extract the hub gene in the PPI network to make further predictions [ 49 ]. Tarbase and mirTarbase determined potential regulatory miRs for differentially expressed genes [ 49 ]. Li et al also investigated potential drug molecules using Enrichr with the Drug Signatures database (DSigDB) and examined gene-disease association via NetworkAnalyst with the DisGeNET database [ 49 ].…”

Biological analysis of the potential pathogenic mechanisms of Infectious COVID-19 and Guillain-Barré syndrome

“…After careful selection, it has been determined that FOXC1 and GATA2 are the most significant transcription factors in the TF-gene network. In previous bioinformatics analyses, numerous researchers have observed that among the identified TFs, FOXC1 and GATA2 have been established as crucial regulatory factors in COVID-19 (41)(42)(43). Their association with GBS is relatively limited.…”