Omics-Assisted Biomarkers Identification and Docking-Based Therapeutic Exploration of Moringa Phytoconstituents in Chronic Obstructive Pulmonary Disease

Abstract Identification of accurate biomarkers is still particularly urgent for improving the poor survival of chronic obstructive pulmonary disease (COPD) patients. In this investigation, we aimed to identity the potential biomarkers in COPD via bioinformatics and next generation sequencing (NGS) data analysis. In this investigation, the differentially expressed genes (DEGs) in COPD were identified using NGS dataset (GSE239897) from Gene Expression Omnibus (GEO) database. Subsequently, gene ontology (GO) and pathway enrichment analysis was conducted to evaluate the underlying molecular mechanisms involved in progression of COPD. Protein-protein interaction (PPI), modules, miRNA-hub gene regulatory network, TF-hub gene regulatory network and drug-hub gene interaction network analysis were performed to identify miRNAs, TFs and drugs. The receiver operating characteristic (ROC) analysis was performed to determine the diagnostic value of hub genes. ADME, toxicity prediction and molecular docking were used to identify potential inhibitors of LMNA, MYC, PHGDH and SHMT2. A total of 956overlapping DEGs (478 up regulated and 478 down regulated genes) were identified in the NGS dataset. DEGs were mainly associated with GO functional terms and pathways in cellular response to stimulus. response to stimulus, immune system and neutrophil degranulation. Based on the data of protein-protein interaction (PPI), the top 10 hub genes (5 up regulated and 5 down regulated) were ranked, including MYC, LMNA, VCAM1, MAPK6, DDX3X, SHMT2, PHGDH, S100A9, FKBP5 and RPS6KA2. The miRNA-hub gene regulatory network and TF-hub gene regulatory network showed that hsa-mir-410-3p, hsa-mir-539-5p, BRCA1 and ESR1 might play an important role in the pathogensis of COPD. The drug-hub gene interaction network showed that Sulindac, Infliximab, Norfloxacin and Gemcitabine predicted therapeutic drugs for the COPD. Our study indicates that diagnostic biomarkers were the basis of the molecular mechanism of COPD and might be potential therapeutic targets. ADME, toxicity prediction and molecular docking screened out moringa phytoconstituents, including Beta-Tocopherol, Procyanidin A2, Vicenin 2, Ellagic acid and Aurantiamide Acetate and possible mechnisum of action,were predicted. Further mechanistic studies of the pathogenesis and treatment of COPD might be able to identify new therapeutic targets.