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Global Protein−Protein Interaction Network in the Human Pathogen Mycobacterium tuberculosis H37Rv

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posted on 03.12.2010, 00:00 by Yi Wang, Tao Cui, Cong Zhang, Min Yang, Yuanxia Huang, Weihui Li, Lei Zhang, Chunhui Gao, Yang He, Yuqing Li, Feng Huang, Jumei Zeng, Cheng Huang, Qiong Yang, Yuxi Tian, Chunchao Zhao, Huanchun Chen, Hua Zhang, Zheng-Guo He
Analysis of the protein−protein interaction network of a pathogen is a powerful approach for dissecting gene function, potential signal transduction, and virulence pathways. This study looks at the construction of a global protein−protein interaction (PPI) network for the human pathogen Mycobacterium tuberculosis H37Rv, based on a high-throughput bacterial two-hybrid method. Almost the entire ORFeome was cloned, and more than 8000 novel interactions were identified. The overall quality of the PPI network was validated through two independent methods, and a high success rate of more than 60% was obtained. The parameters of PPI networks were calculated. The average shortest path length was 4.31. The topological coefficient of the M. tuberculosis B2H network perfectly followed a power law distribution (correlation = 0.999; R-squared = 0.999) and represented the best fit in all currently available PPI networks. A cross-species PPI network comparison revealed 94 conserved subnetworks between M. tuberculosis and several prokaryotic organism PPI networks. The global network was linked to the protein secretion pathway. Two WhiB-like regulators were found to be highly connected proteins in the global network. This is the first systematic noncomputational PPI data for the human pathogen, and it provides a useful resource for studies of infection mechanisms, new signaling pathways, and novel antituberculosis drug development.

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