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Comparative Study of Circadian Oscillatory Network Models of Drosophila

Comparative Study of Circadian Oscillatory Network Models of Drosophila The circadian clock of Drosophila is a model pathway for research in biological clock mechanisms, both with traditional experimental approaches and with emerging systems biology approaches utilizing mathematical modeling and in silico computer simulation. Dynamic diurnal oscillations are achieved by the complex interaction of components as a system, and mathematical reconstruction has proven to be an invaluable means of understanding such systematic behavior. In this study, we implemented eight published models of the Drosophila circadian clock in Systems Biology Markup Language (SBML) for comparative systems biology studies using E-Cell Simulation Environment version 3, to examine the system-level requirements for the clock mechanism to be robust, by calculating the period and amplitude sensitivity coefficients with simulation experiments. While all models were generally robust as determined by the network topology of the oscillatory feedback loop structure, existing models place relatively strong emphasis on transcription regulation, although this is a limitation on robustness. We suggest that more comprehensive modeling including protein phosphorylation, polymerization, and nuclear transport with regard to amplitude sensitivity will be necessary for understanding the light entrainment and temperature compensation of circadian clocks. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Artificial Life MIT Press

Comparative Study of Circadian Oscillatory Network Models of Drosophila

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Publisher
MIT Press
Copyright
© 2008 Massachusetts Institute of Technology
Subject
Articles
ISSN
1064-5462
eISSN
1530-9185
DOI
10.1162/artl.2008.14.1.29
pmid
18171129
Publisher site
See Article on Publisher Site

Abstract

The circadian clock of Drosophila is a model pathway for research in biological clock mechanisms, both with traditional experimental approaches and with emerging systems biology approaches utilizing mathematical modeling and in silico computer simulation. Dynamic diurnal oscillations are achieved by the complex interaction of components as a system, and mathematical reconstruction has proven to be an invaluable means of understanding such systematic behavior. In this study, we implemented eight published models of the Drosophila circadian clock in Systems Biology Markup Language (SBML) for comparative systems biology studies using E-Cell Simulation Environment version 3, to examine the system-level requirements for the clock mechanism to be robust, by calculating the period and amplitude sensitivity coefficients with simulation experiments. While all models were generally robust as determined by the network topology of the oscillatory feedback loop structure, existing models place relatively strong emphasis on transcription regulation, although this is a limitation on robustness. We suggest that more comprehensive modeling including protein phosphorylation, polymerization, and nuclear transport with regard to amplitude sensitivity will be necessary for understanding the light entrainment and temperature compensation of circadian clocks.

Journal

Artificial LifeMIT Press

Published: Jan 1, 2008

Keywords: Systems biology; circadian rhythm; Drosophila ; mathematical models; cell simulation

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