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Open Access Highly Accessed Research article

A logic-based diagram of signalling pathways central to macrophage activation

Sobia Raza1, Kevin A Robertson13, Paul A Lacaze1, David Page1, Anton J Enright2, Peter Ghazal13* and Tom C Freeman1*

Author Affiliations

1 Division of Pathway Medicine, University of Edinburgh, The Chancellor's Building, College of Medicine, 49 Little France Crescent, Edinburgh, EH16 4SB, UK

2 Computation and Functional Genomics Laboratory, Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK

3 Centre for Systems Biology, University of Edinburgh, Darwin Building, King's Building Campus, Mayfield Road, Edinburgh, EH9 3JU, UK

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BMC Systems Biology 2008, 2:36  doi:10.1186/1752-0509-2-36

Published: 23 April 2008

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-κB 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.

Conclusion

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.