title: In silico prediction of protein-protein interactions in human macrophages.
abstract: BACKGROUND
  Protein-protein interaction (PPI) network analyses are highly valuable in deciphering and understanding the intricate organisation of cellular functions. Nevertheless, the majority of available protein-protein interaction networks are context-less, i.e. without any reference to the spatial, temporal or physiological conditions in which the interactions may occur. In this work, we are proposing a protocol to infer the most likely protein-protein interaction (PPI) network in human macrophages.
  
  
  RESULTS
  We integrated the PPI dataset from the Agile Protein Interaction DataAnalyzer (APID) with different meta-data to infer a contextualized macrophage-specific interactome using a combination of statistical methods. The obtained interactome is enriched in experimentally verified interactions and in proteins involved in macrophage-related biological processes (i.e. immune response activation, regulation of apoptosis). As a case study, we used the contextualized interactome to highlight the cellular processes induced upon Mycobacterium tuberculosis infection.
  
  
  CONCLUSIONS
  Our work confirms that contextualizing interactomes improves the biological significance of bioinformatic analyses. More specifically, studying such inferred network rather than focusing at the gene expression level only, is informative on the processes involved in the host response. Indeed, important immune features such as apoptosis are solely highlighted when the spotlight is on the protein interaction level.
authors.affiliation: LIVGM + Laboratory of Medical Parasitology, Biotechnology and Biomolecules, Institut Pasteur de Tunis, Avenue Jugurtha, Tunis, Tunisia. souiai@gmail.com.
authors.forename: Oussema
authors.initials: O
authors.lastname: Souiai
authors.forename: Fatma
authors.initials: F
authors.lastname: Guerfali
authors.forename: Slimane
authors.initials: S
authors.lastname: Ben Miled
authors.forename: Christine
authors.initials: C
authors.lastname: Brun
authors.forename: Alia
authors.initials: A
authors.lastname: Benkahla
mesh_terms: D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D019295:Computational Biology; D003198:Computer Simulation; D030562:Databases, Protein; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D018448:Models, Immunological; D058977:Molecular Sequence Annotation; D009169:Mycobacterium tuberculosis / Q000502:physiology; D025941:Protein Interaction Mapping; D015398:Signal Transduction