title: Hi-Jack: a novel computational framework for pathway-based inference of host-pathogen interactions.
abstract: BACKGROUND
  Pathogens infect their host and hijack the host machinery to produce more progeny pathogens. Obligate intracellular pathogens, in particular, require resources of the host to replicate. Therefore, infections by these pathogens lead to alterations in the metabolism of the host, shifting in favor of pathogen protein production. Some computational identification of mechanisms of host-pathogen interactions have been proposed, but it seems the problem has yet to be approached from the metabolite-hijacking angle.
  
  
  RESULTS
  We propose a novel computational framework, Hi-Jack, for inferring pathway-based interactions between a host and a pathogen that relies on the idea of metabolite hijacking. Hi-Jack searches metabolic network data from hosts and pathogens, and identifies candidate reactions where hijacking occurs. A novel scoring function ranks candidate hijacked reactions and identifies pathways in the host that interact with pathways in the pathogen, as well as the associated frequent hijacked metabolites. We also describe host-pathogen interaction principles that can be used in the future for subsequent studies. Our case study on Mycobacterium tuberculosis (Mtb) revealed pathways in human-e.g. carbohydrate metabolism, lipids metabolism and pathways related to amino acids metabolism-that are likely to be hijacked by the pathogen. In addition, we report interesting potential pathway interconnections between human and Mtb such as linkage of human fatty acid biosynthesis with Mtb biosynthesis of unsaturated fatty acids, or linkage of human pentose phosphate pathway with lipopolysaccharide biosynthesis in Mtb.
  
  
  METHODS
  Datasets and codes are available at http://cloud.kaust.edu.sa/Pages/Hi-Jack.aspx
authors.affiliation: Computer, Electrical and Mathematical Sciences and Engineering Division (CEMSE), King Abdullah University of Science and Technology (KAUST), Thuwal, Jeddah 23955-6900, Saudi Arabia.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Kleftogiannis
authors.affiliation: School of Computing, National University of Singapore, 13 Computing Drive, Singapore 117417, Singapore and.
authors.forename: Limsoon
authors.initials: L
authors.lastname: Wong
authors.affiliation: Computer, Electrical and Mathematical Sciences and Engineering Division (CEMSE), King Abdullah University of Science and Technology (KAUST), Thuwal, Jeddah 23955-6900, Saudi Arabia, Computational Bioscience Research Center (CBRC), King Abdullah University of Science and Technology (KAUST), Thuwal, Jeddah 23955-6900, Saudi Arabia.
authors.forename: John A C
authors.initials: JA
authors.lastname: Archer
authors.affiliation: Computer, Electrical and Mathematical Sciences and Engineering Division (CEMSE), King Abdullah University of Science and Technology (KAUST), Thuwal, Jeddah 23955-6900, Saudi Arabia.
authors.forename: Panos
authors.initials: P
authors.lastname: Kalnis
mesh_terms: D000465:Algorithms; D019295:Computational Biology / Q000379:methods*; D054884:Host-Pathogen Interactions; D006801:Humans; D053858:Metabolic Networks and Pathways; D055432:Metabolomics / Q000379:methods*; D009169:Mycobacterium tuberculosis / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D014376:Tuberculosis / Q000378:metabolism* / Q000382:microbiology
chemical_list: D011506:Proteins