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Introducing spatial information into predictive NF-kappa B modelling - an agent-based approach

Pogson, M., Holcombe, M., Smallwood, R. and Qwarnstrom, E. (2008) Introducing spatial information into predictive NF-kappa B modelling - an agent-based approach. Plos One , 3 (6). Art No.e2367 . ISSN 1932-6203

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Nature is governed by local interactions among lower-level sub-units, whether at the cell, organ, organism, or colony level. Adaptive system behaviour emerges via these interactions, which integrate the activity of the sub-units. To understand the system level it is necessary to understand the underlying local interactions. Successful models of local interactions at different levels of biological organisation, including epithelial tissue and ant colonies, have demonstrated the benefits of such 'agent-based' modelling [1-4]. Here we present an agent-based approach to modelling a crucial biological system the intracellular NF-kappa B signalling pathway. The pathway is vital to immune response regulation, and is fundamental to basic survival in a range of species [5-7]. Alterations in pathway regulation underlie a variety of diseases, including atherosclerosis and arthritis. Our modelling of individual molecules, receptors and genes provides a more comprehensive outline of regulatory network mechanisms than previously possible with equation-based approaches [8]. The method also permits consideration of structural parameters in pathway regulation; here we predict that inhibition of NF-kappa B is directly affected by actin filaments of the cytoskeleton sequestering excess inhibitors, therefore regulating steady-state and feedback behaviour.

Item Type: Article
Copyright, Publisher and Additional Information: © 2008 Pogson et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Institution: The University of Sheffield
Academic Units: The University of Sheffield > Faculty of Engineering (Sheffield) > Department of Computer Science (Sheffield)
Depositing User: Miss Anthea Tucker
Date Deposited: 20 Jan 2010 11:29
Last Modified: 05 Jun 2014 01:25
Published Version: http://dx.doi.org/10.1371/journal.pone.0002367
Status: Published
Publisher: Public Library Science
Refereed: Yes
Identification Number: 10.1371/journal.pone.0002367
URI: http://eprints.whiterose.ac.uk/id/eprint/10304

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