Accessible methods for the dynamic time-scale decomposition of biochemical systems

MOTIVATION The growing complexity of biochemical models asks for means to rationally dissect the networks into meaningful and rather independent subnetworks. Such foregoing should ensure an understanding of the system without any heuristics employed. Important for the success of such an approach is its accessibility and the clarity of the presentation of the results. RESULTS In order to achieve this goal, we developed a method which is a modification of the classical approach of time-scale separation. This modified method as well as the more classical approach have been implemented for time-dependent application within the widely used software COPASI. The implementation includes different possibilities for the representation of the results including 3D-visualization. AVAILABILITY The methods are included in COPASI which is free for academic use and available at www.copasi.org. CONTACT irina.surovtsova@bioquant.uni-heidelberg.de SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.

[1]  References , 1971 .

[2]  S. Lam,et al.  The CSP method for simplifying kinetics , 1994 .

[3]  Peter Deuflhard,et al.  Dynamic Dimension Reduction in ODE Models , 1996 .

[4]  B O Palsson,et al.  Mathematical modelling of dynamics and control in metabolic networks. I. On Michaelis-Menten kinetics. , 1984, Journal of theoretical biology.

[5]  Neema Jamshidi,et al.  Description and analysis of metabolic connectivity and dynamics in the human red blood cell. , 2002, Biophysical journal.

[6]  Stephen Gilmore,et al.  Modelling the Influence of RKIP on the ERK Signalling Pathway Using the Stochastic Process Algebra PEPA , 2006, Trans. Comp. Sys. Biology.

[7]  Tamás Turányi,et al.  Time scale and dimension analysis of a budding yeast cell cycle model , 2006, BMC Bioinformatics.

[8]  Habib N. Najm,et al.  Model Reduction and Physical Understanding of Slowly Oscillating Processes: The Circadian Cycle , 2006, Multiscale Model. Simul..

[9]  Thomas Pfeiffer,et al.  Exploring the pathway structure of metabolism: decomposition into subnetworks and application to Mycoplasma pneumoniae , 2002, Bioinform..

[10]  Wolfgang Mackens,et al.  Scientific Computing in Chemical Engineering , 2011 .

[11]  Jason A. Papin,et al.  Analysis of metabolic capabilities using singular value decomposition of extreme pathway matrices. , 2003, Biophysical journal.

[12]  J. Liao,et al.  Control of metabolic pathways by time-scale separation. , 1995, Bio Systems.

[13]  Ursula Kummer,et al.  A New Time-Dependent Complexity Reduction Method for Biochemical Systems , 2005, Trans. Comp. Sys. Biology.

[14]  D. Kell,et al.  Schemes of flux control in a model of Saccharomyces cerevisiae glycolysis. , 2002, European journal of biochemistry.

[15]  Petter Holme,et al.  Subnetwork hierarchies of biochemical pathways , 2002, Bioinform..

[16]  Gene H. Golub,et al.  Matrix computations , 1983 .

[17]  Stefan Schuster,et al.  BIFURCATION ANALYSIS OF CALCIUM OSCILLATIONS: TIME-SCALE SEPARATION, CANARDS, AND FREQUENCY LOWERING , 2001 .

[18]  J Gorecki,et al.  Derivation of a quantitative minimal model from a detailed elementary-step mechanism supported by mathematical coupling analysis. , 2005, The Journal of chemical physics.

[19]  Mudita Singhal,et al.  COPASI - a COmplex PAthway SImulator , 2006, Bioinform..

[20]  Ulrich Maas,et al.  Simplifying chemical kinetics: Intrinsic low-dimensional manifolds in composition space , 1992 .

[21]  Barbara M. Bakker,et al.  Can yeast glycolysis be understood in terms of in vitro kinetics of the constituent enzymes? Testing biochemistry. , 2000, European journal of biochemistry.

[22]  Irina Surovtsova,et al.  Approaches to Complexity Reduction in a Systems Biology Research Environment (SYCAMORE) , 2006, Proceedings of the 2006 Winter Simulation Conference.

[23]  Ulrich Maas,et al.  Intrinsic low-dimensional manifolds of strained and unstrained flames , 1998 .

[24]  Dirk Lebiedz,et al.  Automatic Complexity Analysis and Model Reduction of Nonlinear Biochemical Systems , 2008, CMSB.

[25]  Robert Roskoski Michaelis-Menten Kinetics , 2007 .