Identification and assessment of hub genes and miRNAs coregulatory associated with immune infiltrations and drug interactions in latent tuberculosis based on MicroarrayData analysis, molecular docking, and dynamic simulation

Abstract

Tuberculosis (TB) remains a major global health concern, with the transition from latent to active TB still poorly understood. Therefore, enhancing clinical management and prevention strategies for TB is essential. High-throughput sequencing data of genes and miRNAs from individuals at different TB stages were obtained from NCBI. Differential expression analysis was performed using the R package limma, alongside GO and KEGG analyses. The central regulatory network of miRNAs was visualized with Cytoscape, and relevant genes were validated using ROC analysis. The predicted key genes involved in the transition from latent to active TB, including PLEKHG1, CLPB, DOK4, IL1β, and TLR3, are primarily associated with multicellular organism processes, stimulus-response, GPCR ligand binding, and immune functions. Finally, we screened Celastrol and Cefaclor Anhydrous targeting IL1β as potent anti-inflammatory drug to reduce the inflammation due to TB. These findings were further validated with Molecular dynamic simulation MM-GBSA and PCA analysis. Our study advances the understanding of latent tuberculosis and identifies genes and microRNAs as potential biomarkers for diagnosis, monitoring, and treatment, with broader implications for complex disease research.