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

Anastasia Chasapi; Paulina Wachowicz; Anne Niknejad; Philippe Collin; Andrea Krapp; Elena Cano; Viesturs Simanis; Ioannis Xenarios

doi:10.1371/journal.pone.0134214

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

PLoS One. 2015 Aug 5;10(8):e0134214. doi: 10.1371/journal.pone.0134214. eCollection 2015.

Authors

Anastasia Chasapi¹, Paulina Wachowicz², Anne Niknejad¹, Philippe Collin², Andrea Krapp², Elena Cano², Viesturs Simanis², Ioannis Xenarios³

Affiliations

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 Vital-IT Group, Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland; Swiss-Prot Group, Swiss Institute of Bioinformatics (SIB), Geneva, 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cytokinesis / genetics*
Gene Expression Regulation, Fungal*
Gene Regulatory Networks / genetics*
Models, Genetic*
Mutation
Reproducibility of Results
Schizosaccharomyces / genetics*
Schizosaccharomyces / metabolism
Schizosaccharomyces pombe Proteins / genetics*
Schizosaccharomyces pombe Proteins / metabolism
Signal Transduction / genetics

Substances

Schizosaccharomyces pombe Proteins

Grants and funding

This work was funded by a SINERGIA grant from the Swiss National Science Foundation (CRSII3_132392), a Swiss National Science Foundation grant to VS (31003A_138176) and PC (109454) and State Secretariat for Research and Innovation (SEFRI) for IX and AN. PC contributed to the study while being affiliated to VS's research group, before his association with his current affiliation with the Horizon Discovery Group. The Horizon Discovery Group had no funding role, and no input into the design or execution of the study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.