A Machine Learning Approach to Identify Potential miRNA-Gene Regulatory Network Contributing to the Pathogenesis of SARS-CoV-2 Infection

Abstract

Worldwide, many lives have been lost in the recent outbreak of coronavirus disease. The pathogen responsible for this disease takes advantage of the host machinery to replicate itself and, in turn, causes pathogenesis in humans. Human miRNAs are seen to have a major role in the pathogenesis and progression of viral diseases. Hence, an in-silico approach has been used in this study to uncover the role of miRNAs and their target genes in coronavirus disease pathogenesis. This study attempts to perform the miRNA seq data analysis to identify the potential differentially expressed miRNAs. Considering only the experimentally proven interaction databases TarBase, miRTarBase, and miRecords, the target genes of the miRNAs have been identified from the mirNET analytics platform. The identified hub genes were subjected to gene ontology and pathway enrichment analysis using EnrichR. It is found that a total of 9 miRNAs are deregulated, out of which 2 were upregulated (hsa-mir-3614-5p and hsa-mir-3614-3p) and 7 were downregulated (hsa-mir-17-5p, hsa-mir-106a-5p, hsa-mir-17-3p, hsa-mir-181d-5p, hsa-mir-93-3p, hsa-mir-28-5p, and hsa-mir-100-5p). These miRNAs help us to classify the diseased and healthy control patients accurately. Moreover, it is also found that crucial target genes (UBC and UBB) of 4 signature miRNAs interact with viral replicase polyprotein 1ab of SARS-Coronavirus. As a result, it is noted that the virus hijacks key immune pathways like various cancer and virus infection pathways and molecular functions such as ubiquitin ligase binding and transcription corepressor and coregulator binding.

Keywords: COVID; Machine learning; Network analysis; SARS-CoV-2; miRNA-gene network; microRNA(miRNA).