Journal Article

Model-based analysis of interferon-β induced signaling pathway

Jaroslaw Smieja, Mohammad Jamaluddin, Allan R. Brasier and Marek Kimmel

in Bioinformatics

Volume 24, issue 20, pages 2363-2369
Published in print October 2008 | ISSN: 1367-4803
Published online August 2008 | e-ISSN: 1460-2059 | DOI:
Model-based analysis of interferon-β induced signaling pathway

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Motivation: Interferon-β induced JAK-STAT signaling pathways contribute to mucosal immune recognition and an anti-viral state. Though the main molecular mechanisms constituting these pathways are known, neither the detailed structure of the regulatory network, nor its dynamics has yet been investigated. The objective of this work is to build a mathematical model for the pathway that would serve two purposes: (1) to reproduce experimental results in simulation of both early and late response to Interferon-β stimulation and (2) to explain experimental phenomena generating new hypotheses about regulatory mechanisms that cannot yet be tested experimentally.

Results: Experimentally determined time dependent changes in the major components of this pathway were used to build a mathematical model describing pathway dynamics in the form of ordinary differential equations. The experimental results suggested existence of unknown negative control mechanisms that were tested numerically using the model. Together, experimental and numerical data show that the epithelial JAK-STAT pathway might be subjected to previously unknown dynamic negative control mechanisms: (1) activation of dormant phosphatases and (2) inhibition of nuclear import of IRF1.

Availability: The model, written in Matlab, is available online at


Supplementary information: Supplementary data are available at Bioinformatics online.

Journal Article.  5768 words.  Illustrated.

Subjects: Bioinformatics and Computational Biology

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