Subnetwork analysis reveals dynamic features of complex (bio)chemical networks

被引:78
作者
Conradi, Carsten
Flockerzi, Dietrich
Raisch, Jorg
Stelling, Jorg
机构
[1] Max Planck Inst Dynam Complex Tech Syst, D-39106 Magdeburg, Germany
[2] Tech Univ Berlin, Fachgebeit Regelungssyst, D-10587 Berlin, Germany
[3] Swiss Fed Inst Technol, Swiss Fes Bioinformat, CH-8092 Zurich, Switzerland
[4] Swiss Fed Inst Technol, Inst Computat Sci, CH-8092 Zurich, Switzerland
关键词
reaction network; structure; elementary flux mode; bistability;
D O I
10.1073/pnas.0705731104
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
In analyzing and mathematical modeling of complex (bio)chemical reaction networks, formal methods that connect network structure and dynamic behavior are needed because often, quantitative knowledge of the networks is very limited. This applies to many important processes in cell biology. Chemical reaction network theory allows for the classification of the potential network behavior-for instance, with respect to the existence of multiple steady states-but is computationally limited to small systems. Here, we show that by analyzing subnetworks termed elementary flux modes, the applicability of the theory can be extended to more complex networks. For an example network inspired by cell cycle control in budding yeast, the approach allows for model discrimination, identification of key mechanisms for multistationarity, and robustness analysis. The presented methods will be helpful in modeling and analyzing other complex reaction networks.
引用
收藏
页码:19175 / 19180
页数:6
相关论文
共 26 条
[1]   Bifurcation analysis of a model of the budding yeast cell cycle [J].
Battogtokh, D ;
Tyson, JJ .
CHAOS, 2004, 14 (03) :653-661
[2]   Interlinked fast and slow positive feedback loops drive reliable cell decisions [J].
Brandman, O ;
Ferrett, JE ;
Li, R ;
Meyer, T .
SCIENCE, 2005, 310 (5747) :496-498
[3]   STOICHIOMETRIC NETWORK ANALYSIS [J].
CLARKE, BL .
CELL BIOPHYSICS, 1988, 12 :237-253
[4]   Using chemical reaction network theory to discard a kinetic mechanism hypothesis [J].
Conradi, C ;
Saez-Rodriguez, J ;
Gilles, ED ;
Raisch, J .
IEE PROCEEDINGS SYSTEMS BIOLOGY, 2005, 152 (04) :243-248
[5]  
CONRADI C, 2006, P 5 MATH MOD
[6]   Understanding bistability in complex enzyme-driven reaction networks [J].
Craciun, Gheorghe ;
Tang, Yangzhong ;
Feinberg, Martin .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (23) :8697-8702
[7]   How catalytic mechanisms reveal themselves in multiple steady-state data: I. Basic principles [J].
Ellison, P ;
Feinberg, M .
JOURNAL OF MOLECULAR CATALYSIS A-CHEMICAL, 2000, 154 (1-2) :155-167
[8]  
ELLISON P, 1998, THESIS U ROCHESTER R
[10]   CHEMICAL-REACTION NETWORK STRUCTURE AND THE STABILITY OF COMPLEX ISOTHERMAL REACTORS .1. THE DEFICIENCY-ZERO AND DEFICIENCY-ONE THEOREMS [J].
FEINBERG, M .
CHEMICAL ENGINEERING SCIENCE, 1987, 42 (10) :2229-2268