Drug repurposing using bulk RNA-seq based on key genes involved in inflammatory bowel disease

Inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis, is a chronic inflammatory disorder of the digestive tract characterized by alternating periods of inflammation and remission. The exact cause of IBD is unknown, but it is generally believed that factors such as bacterial infection, changes in the immune system, and genetic changes can lead to the development of the disease (Collij et al, ۲۰۱۶). IBD is usually accompanied by symptoms such as persistent diarrhea, abdominal pain, rectal bleeding or bloody stools, weight loss, and fatigue. Approximately ۱.۶ million people in the United States are affected by this disease, with a higher prevalence in developed European countries, reaching ۲ million. Interestingly, the incidence of IBD is increasing in developing countries such as South America, Asia, Africa, and Eastern Europe (Wehkamp et al, ۲۰۱۶). In other words, epidemiological trends of IBD in developing countries due to industrialization suggest that environmental factors may play an important role in the development of IBD, especially in genetically susceptible individuals (Ramos and Papadakis, ۲۰۱۹). Using the scRNA-seq technique, the expression signature of the disease is identified, and therefore this expression pattern can be used for drug retargeting (Garrido-Trigo et al, ۲۰۲۳). This study used a computational drug repurposing pipeline to discover candidate drugs based on IBD differential gene expression signatures derived from RNA sequencing data. The transcriptional sample of whole mucosa was compared with accession code GSE۲۴۵۷۶۴ from the GEO database (https://www.ncbi.nlm.nih.gov/geo/). ۱۲ whole mucosa samples of people with IBD and ۱۰ whole mucosa samples of healthy people were analyzed. Differentially expressed genes (DEGs) between whole mucosa samples of IBD subjects and whole mucosa samples of healthy subjects were obtained using GEO۲R. Then, the integrated library of network-based signatures (LINCS) was used to identify potential drugs that can reverse the expression of DEGs. Then, by reviewing the significant literature and drug bank studies (https://go.drugbank.com), the top-ranked drugs with the highest p-value were selected. The study identified ۲۵۰ genes commonly affected by the disease. Among them, genes with |log۲FC| > ۱ and a P-value of < ۰.۰۵ were identified as DEGs. And a network of the main genes involved in the disease was drawn through string(https://cytoscape.org/), and then the selected small molecule was also selected based on its effect on the genes involved in the disease. The results of the data analysis in this study showed that the PIK-۷۵ small molecule can have a positive effect in the treatment of IBD. PIK-۷۵ is a small molecule is a preferential p۱۱۰ alpha/gamma PI۳K inhibitor. And it targets the PIK۳CA gene, and by targeting it, it could help improve the symptoms of IBD.

کلیدواژه ها:

drug repurposing ، bulk RNA-seq ، inflammatory bowel disease