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  From Binary to Multivalued to Continuous Models: The Iac Operon as a Case Study

Franke, R., Theis, F., & Klamt, S. (2010). From Binary to Multivalued to Continuous Models: The Iac Operon as a Case Study. Journal of Integrative Bioinformatics, 7(1), 151. doi:10.2390/biecoll-jib-2010-151.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0013-912A-F Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002C-8B96-F
Genre: Journal Article

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534138_jib_2010.pdf (Publisher version), 984KB
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 Creators:
Franke, R.1, Author
Theis, F.J.1, Author
Klamt, S.2, Author              
Affiliations:
1Helmholtz Centre for Infection Research,Department of Chemical Biology, Braunschweig, GermanyHelmholtz Centre MunichInstitute for Bioinformatics and Systems BiologyGerman Research Center for Environmental HealthNeuherberg, Germany, ou_persistent22              
2Analysis and Redesign of Biological Networks, Max Planck Institute for Dynamics of Complex Technical Systems, Max Planck Society, ou_1738139              

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 Abstract: Using the lac operon as a paradigmatic example for a gene regulatory system in prokaryotes, we demonstrate how qualitative knowledge can be initially captured using simple discrete (Boolean) models and then stepwise refined to multivalued logical models and finally to continuous (ODE) models. At all stages, signal transduction and transcriptional regulation is integrated in the model description. We first show the potential benefit of a discrete binary approach and discuss then problems and limitations due to indeterminacy arising in cyclic networks. These limitations can be partially circumvented by using multilevel logic as generalization of the Boolean framework enabling one to formulate a more realistic model of the lac operon. Ultimately a dynamic description is needed to fully appreciate the potential dynamic behavior that can be induced by regulatory feedback loops. As a very promising method we show how the use of multivariate polynomial interpolation allows transformation of the logical network into a system of ordinary differential equations (ODEs), which then enables the analysis of key features of the dynamic behavior. [accessed 2013 July 2nd]

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Language(s): eng - English
 Dates: 2010
 Publication Status: Published in print
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 Rev. Method: Peer
 Identifiers: eDoc: 534138
DOI: 10.2390/biecoll-jib-2010-151
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Title: Journal of Integrative Bioinformatics
Source Genre: Journal
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Pages: - Volume / Issue: 7 (1) Sequence Number: - Start / End Page: 151 Identifier: -