Identification of biomarkers, pathways, and potential therapeutic targets for heart failure using next-generation sequencing data and bioinformatics analysis.

BACKGROUND: Heart failure (HF) is the most common cardiovascular diseases and the leading cause of cardiovascular diseases related deaths. Increasing molecular targets have been discovered for HF prognosis and therapy. However, there is still an urgent need to identify novel biomarkers. Therefore, we evaluated biomarkers that might aid the diagnosis and treatment of HF. METHODS: We searched next-generation sequencing (NGS) dataset (GSE161472) and identified differentially expressed genes (DEGs) by comparing 47 HF samples and 37 normal control samples using limma in R package. Gene ontology (GO) and pathway enrichment analyses of the DEGs were performed using the g: Profiler database. The protein-protein interaction (PPI) network was plotted with Human Integrated Protein-Protein Interaction rEference (HiPPIE) and visualized using Cytoscape. Module analysis of the PPI network was done using PEWCC1. Then, miRNA-hub gene regulatory network and TF-hub gene regulatory network were constructed by Cytoscape software. Finally, we performed receiver operating characteristic (ROC) curve analysis to predict the diagnostic effectiveness of the hub genes. RESULTS: A total of 930 DEGs, 464 upregulated genes and 466 downregulated genes, were identified in HF. GO and REACTOME pathway enrichment results showed that DEGs mainly enriched in localization, small molecule metabolic process, SARS-CoV infections, and the citric acid tricarboxylic acid (TCA) cycle and respiratory electron transport. After combining the results of the PPI network miRNA-hub gene regulatory network and TF-hub gene regulatory network, 10 hub genes were selected, including heat shock protein 90 alpha family class A member 1 (HSP90AA1), arrestin beta 2 (ARRB2), myosin heavy chain 9 (MYH9), heat shock protein 90 alpha family class B member 1 (HSP90AB1), filamin A (FLNA), epidermal growth factor receptor (EGFR), phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), cullin 4A (CUL4A), YEATS domain containing 4 (YEATS4), and lysine acetyltransferase 2B (KAT2B). CONCLUSIONS: This discovery-driven study might be useful to provide a novel insight into the diagnosis and treatment of HF. However, more experiments are needed in the future to investigate the functional roles of these genes in HF.

Potential Molecular Mechanisms and Remdesivir Treatment for Acute Respiratory Syndrome Corona Virus 2 Infection/COVID 19 Through RNA Sequencing and Bioinformatics Analysis.

INTRODUCTION: Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) infections (COVID 19) is a progressive viral infection that has been investigated extensively. However, genetic features and molecular pathogenesis underlying remdesivir treatment for SARS-CoV-2 infection remain unclear. Here, we used bioinformatics to investigate the candidate genes associated in the molecular pathogenesis of remdesivir-treated SARS-CoV-2-infected patients. METHODS: Expression profiling by high-throughput sequencing dataset (GSE149273) was downloaded from the Gene Expression Omnibus, and the differentially expressed genes (DEGs) in remdesivir-treated SARS-CoV-2 infection samples and nontreated SARS-CoV-2 infection samples with an adjusted P value of <.05 and a |log fold change| > 1.3 were first identified by limma in R software package. Next, pathway and gene ontology (GO) enrichment analysis of these DEGs was performed. Then, the hub genes were identified by the NetworkAnalyzer plugin and the other bioinformatics approaches including protein-protein interaction network analysis, module analysis, target gene-miRNA regulatory network, and target gene-TF regulatory network. Finally, a receiver-operating characteristic analysis was performed for diagnostic values associated with hub genes. RESULTS: A total of 909 DEGs were identified, including 453 upregulated genes and 457 downregulated genes. As for the pathway and GO enrichment analysis, the upregulated genes were mainly linked with influenza A and defense response, whereas downregulated genes were mainly linked with drug metabolism-cytochrome P450 and reproductive process. In addition, 10 hub genes (VCAM1, IKBKE, STAT1, IL7R, ISG15, E2F1, ZBTB16, TFAP4, ATP6V1B1, and APBB1) were identified. Receiver-operating characteristic analysis showed that hub genes (CIITA, HSPA6, MYD88, SOCS3, TNFRSF10A, ADH1A, CACNA2D2, DUSP9, FMO5, and PDE1A) had good diagnostic values. CONCLUSION: This study provided insights into the molecular mechanism of remdesivir-treated SARS-CoV-2 infection that might be useful in further investigations.