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基于重新加权的蛋白质-蛋白质相互作用网络和吸引子算法的系统性表达谱分析挖掘活动性肺结核中失调的模块。

Systematic expression profiling analysis mines dys-regulated modules in active tuberculosis based on re-weighted protein-protein interaction network and attract algorithm.

作者信息

Sun Ying, Weng Yan, Zhang Ying, Yan Xiang, Guo Lei, Wang Jia, Song Xin, Yuan Ying, Chang Fu-Ye, Wang Chun-Ling

机构信息

Department of Cadres' Ward, China Meitan General Hospital, Beijing 100028, China.

Department of Gastroenterology, China Meitan General Hospital, Beijing 100028, China.

出版信息

Microb Pathog. 2017 Jun;107:48-53. doi: 10.1016/j.micpath.2017.03.013. Epub 2017 Mar 18.

Abstract

About 90% of tuberculosis (TB) patients latently infected with Mycobacterium tuberculosis (Mtb) show no symptoms, yet have a 10% chance in lifetime to progress active TB. Nevertheless, current diagnosis approaches need improvement in efficiency and sensitivity. The objective of this work was to detect potential signatures for active TB to further improve the understanding of the biological roles of functional modules involved in this disease. First, targeted networks of active TB and control groups were established via re-weighting protein-protein interaction (PPI) networks using Pearson's correlation coefficient (PCC). Candidate modules were detected from the targeted networks, and the modules with Jaccard score >0.7 were defined as attractors. After that, identification of dys-regulated modules was conducted from the attractors using attract method, Subsequently, gene oncology (GO) enrichment analyses were implemented for genes in the dys-regulated modules. We obtained 33 and 65 candidate modules from the targeted networks of control and active TB groups, respectively. Overall, 13 attractors were identified. Using the cut-off criteria of false discovery rate <0.05, there were 4 dys-regulated modules (Module 1, 2, 3, and 4). Based on the GO annotation results, genes in Modules 1, 2 and 4 were only involved in translation. Most genes in Module 1, 2 and 4 were associated with ribosomes. Accordingly, these dys-regulated modules might serve as potential biomarkers of active TB, facilitating the development for a more efficient, and sensitive diagnostic assay for active TB.

摘要

约90%潜伏感染结核分枝杆菌(Mtb)的结核病(TB)患者没有症状,但一生中发展为活动性结核病的几率为10%。然而,目前的诊断方法在效率和敏感性方面仍需改进。这项工作的目的是检测活动性结核病的潜在特征,以进一步加深对该疾病相关功能模块生物学作用的理解。首先,通过使用皮尔逊相关系数(PCC)对蛋白质-蛋白质相互作用(PPI)网络重新加权,建立活动性结核病和对照组的靶向网络。从靶向网络中检测候选模块,将杰卡德评分>0.7的模块定义为吸引子。之后,使用吸引子方法从吸引子中识别失调模块。随后,对失调模块中的基因进行基因本体论(GO)富集分析。我们分别从对照组和活动性结核病组的靶向网络中获得了33个和65个候选模块。总体而言,共识别出13个吸引子。使用错误发现率<0.05的截断标准,有4个失调模块(模块1、2、3和4)。根据GO注释结果,模块1、2和4中的基因仅参与翻译过程。模块1、2和4中的大多数基因与核糖体相关。因此,这些失调模块可能作为活动性结核病的潜在生物标志物,有助于开发更高效、更敏感的活动性结核病诊断检测方法。

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