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Bioinformatics Advance Access published online on August 7, 2006
Bioinformatics, doi:10.1093/bioinformatics/btl432
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© The Author (2006). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received May 10, 2006
Revised July 27, 2006
Accepted August 3, 2006

Article

Few crucial links assure checkpoint efficiency in the yeast cell-cycle network

Gautier Stoll 1, Jacques Rougemont 2, and Félix Naef 3 *

1 Swiss Institute of Experimental Cancer Research (ISREC) and NCCR Molecular Oncology, CH-1066 Epalinges, Switzerland
2 Swiss Institute of Bioinformatics (SIB), CH-1015 Lausanne, Switzerland
3 Swiss Institute of Experimental Cancer Research (ISREC) and NCCR Molecular Oncology, CH-1066 Epalinges, Switzerland; Ecole Polytechnique Fédérale de Lausanne (EPFL), School of Life Sciences, CH-1015 Lausanne, Switzerland; Swiss Institute of Bioinformatics (SIB), CH-1015 Lausanne, Switzerland


  Abstract

Motivation: The ability of cells to complete mitosis with high fidelity relies on elaborate checkpoint mechanisms. We study S and M phase checkpoint responses in silico in the budding yeast with a stochastic dynamical model for the cell-cycle. We aim to provide an unbiased functional classification of network interactions that reflect the contribution of each link to checkpoint efficiency in the presence of cellular fluctuations.

Results: We developed an algorithm BNetDyn to compute stochastic dynamical trajectories for an input gene network and its structural perturbations. User specified output measures like the mutual information between trigger and output nodes are then evaluated on the stationary state of the Markov process. Systematic perturbations of the yeast cell cycle model by Li et al. classify each link according to its effect on checkpoint efficiencies and stabilities of the main cell-cycle phases. This points to the crosstalk in the cascades downstream of the SBF/MBF transcription activator complexes as determinant for checkpoint optimality; a finding that consistently reflects recent experiments. Finally our stochastic analysis emphasizes how dynamical stability in the yeast cell-cycle network crucially relies on backward inhibitory circuits next to forward induction.

Availability: C++ source code and network models can be downloaded at http://www.vital-it.ch/Software/.

Associate Editor: Thomas Lengauer
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