Model-based analysis of interferon-β induced signaling pathway

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

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2363-2369
Number of pages7
JournalBioinformatics
Volume24
Issue number20
DOIs
StatePublished - Oct 2008

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Computational Theory and Mathematics
  • Computer Science Applications
  • Computational Mathematics
  • Statistics and Probability

Cite this

Smieja, J., Jamaluddin, M., Brasier, A. R., & Kimmel, M. (2008). Model-based analysis of interferon-β induced signaling pathway. Bioinformatics, 24(20), 2363-2369. https://doi.org/10.1093/bioinformatics/btn400