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Bioinformatics Advance Access originally published online on April 14, 2008
Bioinformatics 2008 24(11):1374-1380; doi:10.1093/bioinformatics/btn135
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© The Author 2008. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Implementation of a regulatory gene network to simulate the TH1/2 differentiation in an agent-based model of hypersensitivity reactions

Daniele Santoni 1,2,{dagger}, Marco Pedicini 1 and Filippo Castiglione 1,*,{dagger}

1Institute for Computing Applications ‘M. Picone’, National Research Council (CNR), V.le del Policlinico, 137 – 00161 Rome, Italy and 2Department of Genetics and Molecular Biology, University of Rome ‘La Sapienza’, P. le A. Moro 5, 00185 Rome, Italy

*To whom correspondence should be addressed.


  Abstract

Motivation: An unbalanced differentiation of T helper cells from precursor type TH0 to the TH1 or TH2 phenotype in immune responses often leads to a pathological condition. In general, immune reactions biased toward TH1 responses may result in auto-immune diseases, while enhanced TH2 responses may cause allergic reactions. The aim of this work is to integrate a gene network of the TH differentiation in an agent-based model of the hyper-sensitivity reaction. The implementation of such a system introduces a second level of description beyond the mesoscopic level of the inter-cellular interaction of the agent-based model. The intra-cellular level consists in the cell internal dynamics of gene activation and transcription. The gene regulatory network includes genes-related molecules that have been found to be involved in the differentiation process in TH cells.

Results: The simulator reproduces the hallmarks of an IgE-mediated hypersensitive reaction and provides an example of how to combine the mesoscopic level description of immune cells with the microscopic gene-level dynamics.

Availability: The basic version of the simulator of the immune response can be downloaded here: http://www.iac.cnr.it/~filippo/C-ImmSim.html

Contact: f.castiglione{at}iac.cnr.it

Supplementary information: Supplementary data are available at Bioinformatics online.

{dagger} These authors wish it to be known that, in their opinion, the first and third authors should be regarded as joint First Authors.

Associate Editor: Trey Ideker

Received on January 28, 2008; revised on March 14, 2008; accepted on April 9, 2008

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