An Extended,Boolean Model of the Septation Initiation Network in S.Pombe Provides Insights into Its Regulation |
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| Authors: | Anastasia Chasapi Paulina Wachowicz Anne Niknejad Philippe Collin Andrea Krapp Elena Cano Viesturs Simanis Ioannis Xenarios |
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| Institution: | 1. Vital-IT Group, Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland.; 2. Cell cycle control laboratory, Ecole Polytechnique Fédérale de Lausanne (EPFL), SV-ISREC, Lausanne, Switzerland.; 3. Swiss-Prot Group, Swiss Institute of Bioinformatics (SIB), Geneva, Switzerland.; Cancer Research UK London Research Institute, UNITED KINGDOM, |
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| Abstract: | Cytokinesis in fission yeast is controlled by the Septation Initiation Network (SIN), a protein kinase signaling network using the spindle pole body as scaffold. In order to describe the qualitative behavior of the system and predict unknown mutant behaviors we decided to adopt a Boolean modeling approach. In this paper, we report the construction of an extended, Boolean model of the SIN, comprising most SIN components and regulators as individual, experimentally testable nodes. The model uses CDK activity levels as control nodes for the simulation of SIN related events in different stages of the cell cycle. The model was optimized using single knock-out experiments of known phenotypic effect as a training set, and was able to correctly predict a double knock-out test set. Moreover, the model has made in silico predictions that have been validated in vivo, providing new insights into the regulation and hierarchical organization of the SIN. |
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