Physical understanding of complex multiscale biochemical models via algorithmic simplification: Glycolysis in Saccharomyces cerevisiae

Kourdis, PD; Steuer, R; Goussis, DA

dc.contributor.author	Kourdis, PD	en
dc.contributor.author	Steuer, R	en
dc.contributor.author	Goussis, DA	en
dc.date.accessioned	2014-03-01T01:34:18Z
dc.date.available	2014-03-01T01:34:18Z
dc.date.issued	2010	en
dc.identifier.issn	0167-2789	en
dc.identifier.uri	https://dspace.lib.ntua.gr/xmlui/handle/123456789/20683
dc.subject	Computational singular perturbations	en
dc.subject	Dynamical systems	en
dc.subject	Glycolytic oscillations	en
dc.subject	Model reduction	en
dc.subject.classification	Mathematics, Applied	en
dc.subject.classification	Physics, Multidisciplinary	en
dc.subject.classification	Physics, Mathematical	en
dc.subject.other	Biochemical functions	en
dc.subject.other	Biochemical model	en
dc.subject.other	Cellular reactions	en
dc.subject.other	Computational singular perturbation	en
dc.subject.other	Computational singular perturbations	en
dc.subject.other	Coupled reaction	en
dc.subject.other	Full-scale models	en
dc.subject.other	Glycolytic oscillations	en
dc.subject.other	Large-scale models	en
dc.subject.other	Linear chain	en
dc.subject.other	Low-dimensional manifolds	en
dc.subject.other	Model reduction	en
dc.subject.other	Model reduction techniques	en
dc.subject.other	Multiscales	en
dc.subject.other	Oscillatory regimes	en
dc.subject.other	Redox status	en
dc.subject.other	Saccharomyces cerevisiae	en
dc.subject.other	Time-scales	en
dc.subject.other	Wide spectrum	en
dc.subject.other	Yeast cell	en
dc.subject.other	Dynamical systems	en
dc.subject.other	Models	en
dc.subject.other	Perturbation techniques	en
dc.subject.other	Redox reactions	en
dc.subject.other	Yeast	en
dc.subject.other	Pathology	en
dc.title	Physical understanding of complex multiscale biochemical models via algorithmic simplification: Glycolysis in Saccharomyces cerevisiae	en
heal.type	journalArticle	en
heal.identifier.primary	10.1016/j.physd.2010.06.004	en
heal.identifier.secondary	http://dx.doi.org/10.1016/j.physd.2010.06.004	en
heal.language	English	en
heal.publicationDate	2010	en
heal.abstract	Large-scale models of cellular reaction networks are usually highly complex and characterized by a wide spectrum of time scales, making a direct interpretation and understanding of the relevant mechanisms almost impossible. We address this issue by demonstrating the benefits provided by model reduction techniques. We employ the Computational Singular Perturbation (CSP) algorithm to analyze the glycolytic pathway of intact yeast cells in the oscillatory regime. As a primary object of research for many decades, glycolytic oscillations represent a paradigmatic candidate for studying biochemical function and mechanisms. Using a previously published full-scale model of glycolysis, we show that, due to fast dissipative time scales, the solution is asymptotically attracted on a low dimensional manifold. Without any further input from the investigator, CSP clarifies several long-standing questions in the analysis of glycolytic oscillations, such as the origin of the oscillations in the upper part of glycolysis, the importance of energy and redox status, as well as the fact that neither the oscillations nor cell-cell synchronization can be understood in terms of glycolysis as a simple linear chain of sequentially coupled reactions. (C) 2010 Elsevier B.V. All rights reserved.	en
heal.publisher	ELSEVIER SCIENCE BV	en
heal.journalName	Physica D: Nonlinear Phenomena	en
dc.identifier.doi	10.1016/j.physd.2010.06.004	en
dc.identifier.isi	ISI:000281367300005	en
dc.identifier.volume	239	en
dc.identifier.issue	18	en
dc.identifier.spage	1798	en
dc.identifier.epage	1817	en