title: A logic-based diagram of signalling pathways central to macrophage activation.
abstract: BACKGROUND
  The complex yet flexible cellular response to pathogens is orchestrated by the interaction of multiple signalling and metabolic pathways. The molecular regulation of this response has been studied in great detail but comprehensive and unambiguous diagrams describing these events are generally unavailable. Four key signalling cascades triggered early-on in the innate immune response are the toll-like receptor, interferon, NF-kappaB and apoptotic pathways, which co-operate to defend cells against a given pathogen. However, these pathways are commonly viewed as separate entities rather than an integrated network of molecular interactions.
  
  
  RESULTS
  Here we describe the construction of a logically represented pathway diagram which attempts to integrate these four pathways central to innate immunity using a modified version of the Edinburgh Pathway Notation. The pathway map is available in a number of electronic formats and editing is supported by yEd graph editor software.
  
  
  CONCLUSIONS
  The map presents a powerful visual aid for interpreting the available pathway interaction knowledge and underscores the valuable contribution well constructed pathway diagrams make to communicating large amounts of molecular interaction data. Furthermore, we discuss issues with the limitations and scalability of pathways presented in this fashion, explore options for automated layout of large pathway networks and demonstrate how such maps can aid the interpretation of functional studies.
authors.affiliation: Division of Pathway Medicine, University of Edinburgh, The Chancellor's Building, College of Medicine, 49 Little France Crescent, Edinburgh, EH16 4SB, UK. sobia.raza@ed.ac.uk
authors.forename: Sobia
authors.initials: S
authors.lastname: Raza
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Robertson
authors.forename: Paul A
authors.initials: PA
authors.lastname: Lacaze
authors.forename: David
authors.initials: D
authors.lastname: Page
authors.forename: Anton J
authors.initials: AJ
authors.lastname: Enright
authors.forename: Peter
authors.initials: P
authors.lastname: Ghazal
authors.forename: Tom C
authors.initials: TC
authors.lastname: Freeman
mesh_terms: D000818:Animals; D001296:Audiovisual Aids; D001853:Bone Marrow; D002478:Cells, Cultured; D003196:Computer Graphics; D007113:Immunity, Innate / Q000502:physiology; D007372:Interferons / Q000378:metabolism; D008128:Logic; D008262:Macrophage Activation / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D009000:Monocytes / Q000276:immunology; D016328:NF-kappa B / Q000378:metabolism; D025941:Protein Interaction Mapping / Q000379:methods; D015398:Signal Transduction / Q000276:immunology*; D049490:Systems Biology / Q000379:methods*; D018511:Systems Integration; D051193:Toll-Like Receptors / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000276:immunology / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D051193:Toll-Like Receptors; D007372:Interferons; D048051:p38 Mitogen-Activated Protein Kinases