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An Extended, Boolean Model of the Septation Initiation Network in S.Pombe Provides Insights into Its Regulation.

Chasapi A, Wachowicz P, Niknejad A, Collin P, Krapp A, Cano E, Simanis V, Xenarios I - PLoS ONE (2015)

Bottom Line: In order to describe the qualitative behavior of the system and predict unknown mutant behaviors we decided to adopt a Boolean modeling approach.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.

View Article: PubMed Central - PubMed

Affiliation: Vital-IT Group, Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland.

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.

No MeSH data available.


The extended Boolean SIN model.(A) The initial, prior knowledge network, manually re-constructed from the literature. Purple nodes represent proteins and complexes that take part in the regulation of the SIN, and pink nodes represent AND gates. Blue arrows indicate activation events and orange circles inhibition events. Other logical functions, such as AND, OR and NOT regulatory gates are also encoded in the model. SAC: spindle assembly checkpoint, APC: anaphase-promoting complex, PP: protein phosphatase. (B) The final, optimized model, which uses a 3-node representation of CDK activity. Nodes in green are used as switches, and they are turned on to represent different stages of the cell cycle: interphase, early mitosis and late mitosis. Pink nodes represent AND gates. In the case of the Cdc42p regulatory link towards Byr4p, the regulatory rule can be phrased as “NOT Cdc42p activates Byr4p”.
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pone.0134214.g002: The extended Boolean SIN model.(A) The initial, prior knowledge network, manually re-constructed from the literature. Purple nodes represent proteins and complexes that take part in the regulation of the SIN, and pink nodes represent AND gates. Blue arrows indicate activation events and orange circles inhibition events. Other logical functions, such as AND, OR and NOT regulatory gates are also encoded in the model. SAC: spindle assembly checkpoint, APC: anaphase-promoting complex, PP: protein phosphatase. (B) The final, optimized model, which uses a 3-node representation of CDK activity. Nodes in green are used as switches, and they are turned on to represent different stages of the cell cycle: interphase, early mitosis and late mitosis. Pink nodes represent AND gates. In the case of the Cdc42p regulatory link towards Byr4p, the regulatory rule can be phrased as “NOT Cdc42p activates Byr4p”.

Mentions: The constructed prior knowledge network (PKN) consists of 50 nodes (gene products, proteins and complexes) and 124 directed edges (Fig 2A). The regulatory information is the result of the curation of 67 published scientific papers (S1 table). The most recently published interaction contained in this model is the inhibitory regulation of CDK and Plo1p upon Byr4p recently published by [46].


An Extended, Boolean Model of the Septation Initiation Network in S.Pombe Provides Insights into Its Regulation.

Chasapi A, Wachowicz P, Niknejad A, Collin P, Krapp A, Cano E, Simanis V, Xenarios I - PLoS ONE (2015)

The extended Boolean SIN model.(A) The initial, prior knowledge network, manually re-constructed from the literature. Purple nodes represent proteins and complexes that take part in the regulation of the SIN, and pink nodes represent AND gates. Blue arrows indicate activation events and orange circles inhibition events. Other logical functions, such as AND, OR and NOT regulatory gates are also encoded in the model. SAC: spindle assembly checkpoint, APC: anaphase-promoting complex, PP: protein phosphatase. (B) The final, optimized model, which uses a 3-node representation of CDK activity. Nodes in green are used as switches, and they are turned on to represent different stages of the cell cycle: interphase, early mitosis and late mitosis. Pink nodes represent AND gates. In the case of the Cdc42p regulatory link towards Byr4p, the regulatory rule can be phrased as “NOT Cdc42p activates Byr4p”.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4526654&req=5

pone.0134214.g002: The extended Boolean SIN model.(A) The initial, prior knowledge network, manually re-constructed from the literature. Purple nodes represent proteins and complexes that take part in the regulation of the SIN, and pink nodes represent AND gates. Blue arrows indicate activation events and orange circles inhibition events. Other logical functions, such as AND, OR and NOT regulatory gates are also encoded in the model. SAC: spindle assembly checkpoint, APC: anaphase-promoting complex, PP: protein phosphatase. (B) The final, optimized model, which uses a 3-node representation of CDK activity. Nodes in green are used as switches, and they are turned on to represent different stages of the cell cycle: interphase, early mitosis and late mitosis. Pink nodes represent AND gates. In the case of the Cdc42p regulatory link towards Byr4p, the regulatory rule can be phrased as “NOT Cdc42p activates Byr4p”.
Mentions: The constructed prior knowledge network (PKN) consists of 50 nodes (gene products, proteins and complexes) and 124 directed edges (Fig 2A). The regulatory information is the result of the curation of 67 published scientific papers (S1 table). The most recently published interaction contained in this model is the inhibitory regulation of CDK and Plo1p upon Byr4p recently published by [46].

Bottom Line: In order to describe the qualitative behavior of the system and predict unknown mutant behaviors we decided to adopt a Boolean modeling approach.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.

View Article: PubMed Central - PubMed

Affiliation: Vital-IT Group, Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland.

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.

No MeSH data available.