Integrative Bioinformatics Analysis of Single Cell RNA-Sequencing Data Reveals Key Regulatory Genes and Therapeutic Targets in Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is a chronic digestive disorder with abdominal pain, diarrhea, blood or mucus in the stool. Under various treatments, some patients still have a poor prognosis. Hence, it is necessary to find new valid targets for IBD therapy. The single cell RNA-sequencing data (GSE255243) was acquired from the Gene Expression Omnibus (GEO). In this study, Seurat in R language was used to identify differentially expressed genes (DEGs) between cells of colon biopsies from a non-IBD healthy control and a pan-colitic IBD using. Then, Gene Ontology (GO) and REACTOME pathway enrichment analyses were applied to the selected DEGs. The HIPPIE database and Cytoscape software were used to construct protein-protein interaction (PPI) network and perform modular analysis of the DEGs. A miRNA-hub gene regulatory network, TF-hub gene regulatory network were used to select miRNAs and TFs regulating the expression of hub genes, and drug-hub gene interaction network was utilized to screen potential therapeutic drugs/compounds targeting hub genes. Receiver operating characteristic (ROC) curve to assess the diagnostic efficacy of hub genes. By performing DEGs analysis, total 959 DEGs including 479 up-regulated and 480 down-regulated genes were successfully identified from GSE66360, respectively. And they were mainly enriched in the terms of multicellular organismal process, response to stimulus, class A/1 (Rhodopsin-like receptors) and hemostasis. Based on the data of protein-protein interaction (PPI), the top hub genes were ranked, including SOX2, GPR17, SFN, S100P, YBX2, APP, TUBA1A, VIM, CAV1 and ENG, which showed strong diagnostic potential, as evidenced by ROC curve analysis. MiRNA and TFs may be a potential biomarkers in the analysis of miRNA-hub gene regulatory network and TF-hub gene regulatory network. hsa-miR-34a-3p, hsa-miR-4781-3p, SREBF2 and HINFP are predicted to be associated in IBD. drug-hub gene interaction network analysis predicted Amrinone and Bendroflumethiazide as promising therapeutic candidates for IBD intervention. In conclusion, this study enhances our understanding of IBD pathogenesis by identifying key biomarkers and therapeutic targets, paving the way for future advancements in personalized diagnosis and treatment strategies.