Timing robustness in the budding and fission yeast cell cycles.

Handle URI:
http://hdl.handle.net/10754/596850
Title:
Timing robustness in the budding and fission yeast cell cycles.
Authors:
Mangla, Karan; Dill, David L; Horowitz, Mark A
Abstract:
Robustness of biological models has emerged as an important principle in systems biology. Many past analyses of Boolean models update all pending changes in signals simultaneously (i.e., synchronously), making it impossible to consider robustness to variations in timing that result from noise and different environmental conditions. We checked previously published mathematical models of the cell cycles of budding and fission yeast for robustness to timing variations by constructing Boolean models and analyzing them using model-checking software for the property of speed independence. Surprisingly, the models are nearly, but not totally, speed-independent. In some cases, examination of timing problems discovered in the analysis exposes apparent inaccuracies in the model. Biologically justified revisions to the model eliminate the timing problems. Furthermore, in silico random mutations in the regulatory interactions of a speed-independent Boolean model are shown to be unlikely to preserve speed independence, even in models that are otherwise functional, providing evidence for selection pressure to maintain timing robustness. Multiple cell cycle models exhibit strong robustness to timing variation, apparently due to evolutionary pressure. Thus, timing robustness can be a basis for generating testable hypotheses and can focus attention on aspects of a model that may need refinement.
Citation:
Mangla K, Dill DL, Horowitz MA (2010) Timing Robustness in the Budding and Fission Yeast Cell Cycles. PLoS ONE 5: e8906. Available: http://dx.doi.org/10.1371/journal.pone.0008906.
Publisher:
Public Library of Science (PLoS)
Journal:
PLoS ONE
Issue Date:
1-Feb-2010
DOI:
10.1371/journal.pone.0008906
PubMed ID:
20126540
PubMed Central ID:
PMC2813865
Type:
Article
ISSN:
1932-6203
Sponsors:
This research has been funded in part by a King Abdullah University of Science and Technology (KAUST) research grant under the KAUST-Stanford Academic Excellence Alliance program, and by a seed grant from the Stanford University Department of Computer Science. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Any opinions, findings, and conclusions or recommendations expressed in this paper are those of the authors and do not necessarily reflect the views of any of the funders.
Appears in Collections:
Publications Acknowledging KAUST Support

Full metadata record

DC FieldValue Language
dc.contributor.authorMangla, Karanen
dc.contributor.authorDill, David Len
dc.contributor.authorHorowitz, Mark Aen
dc.date.accessioned2016-02-21T09:35:22Zen
dc.date.available2016-02-21T09:35:22Zen
dc.date.issued2010-02-01en
dc.identifier.citationMangla K, Dill DL, Horowitz MA (2010) Timing Robustness in the Budding and Fission Yeast Cell Cycles. PLoS ONE 5: e8906. Available: http://dx.doi.org/10.1371/journal.pone.0008906.en
dc.identifier.issn1932-6203en
dc.identifier.pmid20126540en
dc.identifier.doi10.1371/journal.pone.0008906en
dc.identifier.urihttp://hdl.handle.net/10754/596850en
dc.description.abstractRobustness of biological models has emerged as an important principle in systems biology. Many past analyses of Boolean models update all pending changes in signals simultaneously (i.e., synchronously), making it impossible to consider robustness to variations in timing that result from noise and different environmental conditions. We checked previously published mathematical models of the cell cycles of budding and fission yeast for robustness to timing variations by constructing Boolean models and analyzing them using model-checking software for the property of speed independence. Surprisingly, the models are nearly, but not totally, speed-independent. In some cases, examination of timing problems discovered in the analysis exposes apparent inaccuracies in the model. Biologically justified revisions to the model eliminate the timing problems. Furthermore, in silico random mutations in the regulatory interactions of a speed-independent Boolean model are shown to be unlikely to preserve speed independence, even in models that are otherwise functional, providing evidence for selection pressure to maintain timing robustness. Multiple cell cycle models exhibit strong robustness to timing variation, apparently due to evolutionary pressure. Thus, timing robustness can be a basis for generating testable hypotheses and can focus attention on aspects of a model that may need refinement.en
dc.description.sponsorshipThis research has been funded in part by a King Abdullah University of Science and Technology (KAUST) research grant under the KAUST-Stanford Academic Excellence Alliance program, and by a seed grant from the Stanford University Department of Computer Science. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Any opinions, findings, and conclusions or recommendations expressed in this paper are those of the authors and do not necessarily reflect the views of any of the funders.en
dc.publisherPublic Library of Science (PLoS)en
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en
dc.subject.meshModels, Biologicalen
dc.titleTiming robustness in the budding and fission yeast cell cycles.en
dc.typeArticleen
dc.identifier.journalPLoS ONEen
dc.identifier.pmcidPMC2813865en
dc.contributor.institutionStanford University, Palo Alto, United Statesen
dc.contributor.institutionStanford University, Palo Alto, United Statesen
kaust.grant.programAcademic Excellence Alliance (AEA)en

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