Comprehensive Identification of Potential Biomarkers Using Next Generation Sequencing Based Bioinformatics and Exploration of Therapeutic Molecules by Molecular Docking Studies for Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is the most common chronic digestive disorders and inflammation in the gastrointestinal tract globally that is characterized by episodes of abdominal pain, diarrhea, bloody stools and weight loss. However, the pathophysiologic mechanisms of IBD have not been thoroughly investigated. To explore potential targets for treatment of IBD, we reorganized and analyzed next generation sequencing (NGS) dataset (GSE186507). The R package DESeq2 tool was used to screen for differentially expressed genes (DEGs) between IBD and normal control samples. We used the g:Profiler database to perform Gene Ontology (GO) enrichment analysis and the REACTOME for pathway enrichment analysis. Protein-protein interaction (PPI) network construction and module analysis were performed to elucidate molecular mechanisms of DEGs and screen hub genes. Then, miRNA-hub gene regulatory network and TF-hub gene regulatory network were associated with IBD were constructed and analyzed. Drug-hub gene interaction network construction and drug prediction analysis were performed. We validated the identified hub genes via receiver operating characteristic (ROC) curve analysis. Finally, molecular docking and ADME studies were performed. A total of 957 DEGs (478 up regulated genes and 479 down regulated genes) were detected in NGS dataset. And they were mainly enriched in the terms of multicellular organismal process, response to stimulus, GPCR ligand binding and immune system. Through analyzing the PPI network, we screened hub genes. Based on the data of PPI network top hub genes were ranked, including IL7R, ERBB2, SMAD1, RPS26, TLE1, HNF4A, CDKN1A, SRPK1, H3C12 and SFN. The regulatory network analysis revealed that microRNAs (miRNAs) include hsa- hsa-mir-3921 and hsa-mir-5685, and transcription factors (TFs) include TTF2 and DNAJC2 might be involved in the development of IBD. 4 drugs molecules were predicted including Pseudoephedrine, Voacamine, Edrophonium and Doxazosin. Receiver operating characteristic curve analysis demonstrated that the hub genes screened for IBD were of good diagnostic Importance. Ochnaflavone as a promising bioflavonoid with strong binding affinity toward ERBB2 and HNF4A. In conclusion, the identified DEGs, particularly the hub genes, strengthen the understanding of the development and progression of IDB, and certain novel genes might be used as candidate target molecules to diagnose, monitor and treat IDB.