In-Silico Identification of Shared Hub-Genes Between Idiopathic Pulmonary Fibrosis and Tuberculosis Diseases & Drug Repurposing

Idiopathic Pulmonary Fibrosis (IPF) and Tuberculosis (TB) are both complicated diseases and gradually increasing their incidence rates worldwide. Some population-based studies reported that TB and IPF diseases stimulate each other. However, in the literature, so far, there is no article that suggested shared molecular mechanisms about their co-occurrence and associated drug molecules as common treatments. This study aimed to explore IPF and TB-causing shared Hub-Genes(sHubGs) focusing on their molecular mechanisms of co-occurrence and associated common drugs for better treatment. Firstly, a LIMMA statistical package and Random Forest-based machine learning approach were utilized to identify 252 shared differentially expressed genes (sDEGs) between IPF and TB that are able to separate both diseases from the control groups. Subsequently, protein-protein interaction (PPI) network analysis revealed top-ranked 10 sDEGs (SOCS3, SELL, IL1RN, IL18RAP, TNFAIP6, RPL8, DRG1, ATP5F1A, PSMA3, and VCP) as sHubGs out of the 252 sDEGs. The sHubGs-set enrichment analysis disclosed some crucial biological processes, molecular functions, signaling pathways and regulatory components as the common molecular mechanisms underlying the development of both diseases. Lastly, this study proposed twelve candidate drug molecules(Dihydroergotamine, Lumacaftor, Amentoflavone, LL3858, Imatinib Mesylate, Galectin3, TD139, Imatinib, Delamanid, Clofazimine, Streptomycin, and Nintedanib) guided by sHubGs as the common treatments for both diseases. Thus, these findings may hold significance for the diagnosis and therapies of both TB and IPF diseases during their co-occurrence.