A continuous-time stochastic Boolean model provides a quantitative description of the budding yeast cell cycle

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dc.contributor.authorLaomettachit, Teeraphanen
dc.contributor.authorKraikivski, Pavelen
dc.contributor.authorTyson, John J.en
dc.date.accessioned2022-12-21T14:47:22Zen
dc.date.available2022-12-21T14:47:22Zen
dc.date.issued2022-12-01en
dc.date.updated2022-12-21T02:23:24Zen
dc.description.abstractThe cell division cycle is regulated by a complex network of interacting genes and proteins. The control system has been modeled in many ways, from qualitative Boolean switching-networks to quantitative differential equations and highly detailed stochastic simulations. Here we develop a continuous-time stochastic model using seven Boolean variables to represent the activities of major regulators of the budding yeast cell cycle plus one continuous variable representing cell growth. The Boolean variables are updated asynchronously by logical rules based on known biochemistry of the cell-cycle control system using Gillespie’s stochastic simulation algorithm. Time and cell size are updated continuously. By simulating a population of yeast cells, we calculate statistical properties of cell cycle progression that can be compared directly to experimental measurements. Perturbations of the normal sequence of events indicate that the cell cycle is 91% robust to random ‘flips’ of the Boolean variables, but 9% of the perturbations induce lethal mistakes in cell cycle progression. This simple, hybrid Boolean model gives a good account of the growth and division of budding yeast cells, suggesting that this modeling approach may be as accurate as detailed reaction-kinetic modeling with considerably less demands on estimating rate constants.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier20302 (Article number)en
dc.identifier.doihttps://doi.org/10.1038/s41598-022-24302-6en
dc.identifier.eissn2045-2322en
dc.identifier.issn2045-2322en
dc.identifier.issue1en
dc.identifier.orcidKraikivski, Pavel [0000-0001-7742-0140]en
dc.identifier.other10.1038/s41598-022-24302-6 (PII)en
dc.identifier.pmid36434030en
dc.identifier.urihttp://hdl.handle.net/10919/112967en
dc.identifier.volume12en
dc.language.isoenen
dc.publisherSpringer Natureen
dc.relation.urihttps://www.ncbi.nlm.nih.gov/pubmed/36434030en
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectBioengineeringen
dc.subjectRare Diseasesen
dc.subject.meshSaccharomycetalesen
dc.subject.meshCell Cycleen
dc.subject.meshCell Divisionen
dc.subject.meshModels, Biologicalen
dc.subject.meshCell Cycle Checkpointsen
dc.titleA continuous-time stochastic Boolean model provides a quantitative description of the budding yeast cell cycleen
dc.title.serialScientific Reportsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherArticleen
dcterms.dateAccepted2022-11-14en
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Scienceen
pubs.organisational-group/Virginia Tech/Science/Dean of Scienceen

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