Department of Biotechnology, School of Biosciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, India.
Front Cell Infect Microbiol. 2022 Oct 5;12:1010771. doi: 10.3389/fcimb.2022.1010771. eCollection 2022.
Multi-drug resistant tuberculosis still remains a major public health crisis globally. With the emergence of newer active tuberculosis disease, the requirement of prolonged treatment time and adherence to therapy till its completion necessitates the search of newer therapeutics, targeting human host factors. The current work utilized statistical meta-analysis of human gene transcriptomes of active pulmonary tuberculosis disease obtained from six public datasets. The meta-analysis resulted in the identification of 2038 significantly differentially expressed genes (DEGs) in the active tuberculosis disease. The gene ontology (GO) analysis revealed that these genes were major contributors in immune responses. The pathway enrichment analyses identified from various human canonical pathways are related to other infectious diseases. In addition, the comparison of the DEGs with the tuberculosis genome wide association study (GWAS) datasets revealed the presence of few genetic variants in their proximity. The analysis of protein interaction networks (human and ) and host directed drug-target interaction network led to new candidate drug targets for drug repurposing studies. The current work sheds light on host genes and pathways enriched in active tuberculosis disease and suggest potential drug repurposing targets for host-directed therapies.
耐多药结核病仍然是全球主要的公共卫生危机。随着新的活动性结核病的出现，需要延长治疗时间并坚持完成治疗，这就需要寻找新的治疗方法，针对人体宿主因素。目前的工作利用来自六个公共数据集的活动性肺结核病患者的人类基因转录组的统计荟萃分析。荟萃分析确定了 2038 个在活动性结核病中显著差异表达的基因（DEGs）。基因本体（GO）分析表明，这些基因是免疫反应的主要贡献者。从各种人类经典途径中鉴定出的途径富集分析与其他传染病有关。此外，将 DEGs 与结核病全基因组关联研究（GWAS）数据集进行比较，发现它们附近存在一些遗传变异。对蛋白质相互作用网络（人类和）和宿主导向药物-靶标相互作用网络的分析导致了重新利用药物进行药物研究的新候选药物靶点。目前的工作揭示了活动性肺结核病中富含的宿主基因和途径，并为宿主导向治疗提供了潜在的药物再利用靶点。
