title: Inferring a protein interaction map of Mycobacterium tuberculosis based on sequences and interologs.
abstract: BACKGROUND
  Mycobacterium tuberculosis is an infectious bacterium posing serious threats to human health. Due to the difficulty in performing molecular biology experiments to detect protein interactions, reconstruction of a protein interaction map of M. tuberculosis by computational methods will provide crucial information to understand the biological processes in the pathogenic microorganism, as well as provide the framework upon which new therapeutic approaches can be developed.
  
  
  RESULTS
  In this paper, we constructed an integrated M. tuberculosis protein interaction network by machine learning and ortholog-based methods. Firstly, we built a support vector machine (SVM) method to infer the protein interactions of M. tuberculosis H37Rv by gene sequence information. We tested our predictors in Escherichia coli and mapped the genetic codon features underlying its protein interactions to M. tuberculosis. Moreover, the documented interactions of 14 other species were mapped to the interactome of M. tuberculosis by the interolog method. The ensemble protein interactions were validated by various functional relationships, i.e., gene coexpression, evolutionary relationship and functional similarity, extracted from heterogeneous data sources. The accuracy and validation demonstrate the effectiveness and efficiency of our framework.
  
  
  CONCLUSIONS
  A protein interaction map of M. tuberculosis is inferred from genetic codons and interologs. The prediction accuracy and numerically experimental validation demonstrate the effectiveness and efficiency of our method. Furthermore, our methods can be straightforwardly extended to infer the protein interactions of other bacterial species.
authors.affiliation: Key Laboratory of Systems Biology, SIBS-Novo Nordisk Translational Research Centre for PreDiabetes, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China. zpliu@sibs.ac.cn
authors.forename: Zhi-Ping
authors.initials: ZP
authors.lastname: Liu
authors.forename: Jiguang
authors.initials: J
authors.lastname: Wang
authors.forename: Yu-Qing
authors.initials: YQ
authors.lastname: Qiu
authors.forename: Ross K K
authors.initials: RK
authors.lastname: Leung
authors.forename: Xiang-Sun
authors.initials: XS
authors.lastname: Zhang
authors.forename: Stephen K W
authors.initials: SK
authors.lastname: Tsui
authors.forename: Luonan
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D004926:Escherichia coli / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000378:metabolism*; D060066:Protein Interaction Maps; D060388:Support Vector Machine