Timing robustness in the budding and fission yeast cell cycles.

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 di...

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Autores principales:	Karan Mangla, David L Dill, Mark A Horowitz
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d314093f11a04492bdbb34c6767abaf5
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spelling	oai:doaj.org-article:d314093f11a04492bdbb34c6767abaf52021-11-25T06:26:13ZTiming robustness in the budding and fission yeast cell cycles.1932-620310.1371/journal.pone.0008906https://doaj.org/article/d314093f11a04492bdbb34c6767abaf52010-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20126540/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Robustness 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.Karan ManglaDavid L DillMark A HorowitzPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 2, p e8906 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Karan Mangla David L Dill Mark A Horowitz Timing robustness in the budding and fission yeast cell cycles.
description	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.
format	article
author	Karan Mangla David L Dill Mark A Horowitz
author_facet	Karan Mangla David L Dill Mark A Horowitz
author_sort	Karan Mangla
title	Timing robustness in the budding and fission yeast cell cycles.
title_short	Timing robustness in the budding and fission yeast cell cycles.
title_full	Timing robustness in the budding and fission yeast cell cycles.
title_fullStr	Timing robustness in the budding and fission yeast cell cycles.
title_full_unstemmed	Timing robustness in the budding and fission yeast cell cycles.
title_sort	timing robustness in the budding and fission yeast cell cycles.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/d314093f11a04492bdbb34c6767abaf5
work_keys_str_mv	AT karanmangla timingrobustnessinthebuddingandfissionyeastcellcycles AT davidldill timingrobustnessinthebuddingandfissionyeastcellcycles AT markahorowitz timingrobustnessinthebuddingandfissionyeastcellcycles
_version_	1718413771524800512

Timing robustness in the budding and fission yeast cell cycles.

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