人类免疫缺陷病毒合并结核杆菌感染者外周血差异表达基因的生物信息学分析

Bioinformatic Analysis of Differentially Expressed Genes in Peripheral Blood of Human Immunodeficiency Virus/Tubercle Bacilli Co-infected Patients

目的分析人类免疫缺陷病毒(HIV)/结核杆菌(TB)感染者外周血基因的生物学网络调控机制及关键蛋白,为HIV/TB感染者的早期诊断和临床治疗提供新依据。方法从基因芯片公共数据库GEO中下载了22例南非HIV感染者和22例HIV/TB感染者的外周血基因芯片数据,将数据导入分析软件QOE、STRING、PANTHER、GenClip等,分析两组患者的基因表达谱、蛋白相互作用网络、分子生物学过程、基因功能等,寻找区别两类患者的关键节点基因。结果两组患者15 529个基因的表达谱相似,44名受试者的基因表达谱具有高度关联性;251个(1.62%)差异表达基因对诊断HIV/TB感染具有良好的诊断能力;RPLP1是蛋白-蛋白相互作用图谱子网络的核心节点;差异表达基因与正向调节外界刺激、细胞内信号通路的转导、中性粒细胞的迁移、人体免疫等有关,主要参与自由基相关凋亡、炎性反应等通路的活化。结论共发现251个差异表达的基因可将单纯HIV感染和HIV/TB感染进行区别,其中差异表达的前40个基因的蛋白-蛋白相互作用网络中所包含的RPLP1基因可能与HIV/TB感染密切关联,主要涉及正向调节外界刺激、细胞内信号通路的转导、中性粒细胞的迁移、人体免疫等生物学功能,为HIV/TB感染的诊断和治疗提供了一定的参考依据。

Objective To analyze the differentially expressed genes in peripheral blood of human immunodeficiency（HIV）/tubercle bacilli co-infected patients and explore the biological regulatory mechanism and network of key proteins,so as to provide new evidence for early diagnosis and clinical treatment of HIV/TB co-infected patients. Methods Microarray gene chip data of HIV/TB co-infected patients were downloaded from public databases GEO and imported into the analysis software GEO,STRING,PANTHER,and Gen Clip. The gene expression profiles,protein interaction networks,processes of molecular biology,and gene functions wereanalyzed. Results The expression profiles of 15 529 genes between the two groups of patients were similar,and gene expression profiles from 44 subjects were highly correlated. The 251 differentially expressed genes had good diagnostic capabilities in the differential diagnosis of HIV/TB infection. RPLP1 might be a key gene in the diagnosis of HIV/TB infection. The differentially expressed genes and positive regulators showed certain functions such as external stimuli,signal transduction pathways in cells,migration of neutrophils,and immunological and other relevant functionalities. Meanwhile,they may also be involved in free radical-related apoptosis,inflammation,and activation pathways. Conclusions A total of 251 differentially expressed genes are found to be able to distinguish simple HIV infection from HIV/TB infection. Protein-protein interaction network of top 40 differential expression genes includes RPLP1 gene,which is possibly associated with HIV/TB co-infection and may be involved in and the positive regulation of external stimuli,signal transduction pathways in cells,migration of neutrophils,and immunological functions. These findings may provide certain evidence for the diagnosis and treatment of HIV/TB infection.