Identifying parameter regions for multistationarity

被引:62
作者
Conradi, Carsten [1 ]
Feliu, Elisenda [2 ]
Mincheva, Maya [3 ]
Wiuf, Carsten [2 ]
机构
[1] HTW Berlin, Life Sci Engn, Berlin, Germany
[2] Univ Copenhagen, Dept Math Sci, Copenhagen, Denmark
[3] Northern Illinois Univ, Dept Math Sci, De Kalb, IL USA
关键词
CHEMICAL-REACTION NETWORKS; MASS-ACTION; MULTIPLE EQUILIBRIA; PERSISTENCE; MULTISTABILITY; DIFFERENTIATION; OSCILLATIONS; BISTABILITY; ELIMINATION; INJECTIVITY;
D O I
10.1371/journal.pcbi.1005751
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Mathematical modelling has become an established tool for studying the dynamics of biological systems. Current applications range from building models that reproduce quantitative data to identifying systems with predefined qualitative features, such as switching behaviour, bistability or oscillations. Mathematically, the latter question amounts to identifying parameter values associated with a given qualitative feature. We introduce a procedure to partition the parameter space of a parameterized system of ordinary differential equations into regions for which the system has a unique or multiple equilibria. The procedure is based on the computation of the Brouwer degree, and it creates a multivariate polynomial with parameter depending coefficients. The signs of the coefficients determine parameter regions with and without multistationarity. A particular strength of the procedure is the avoidance of numerical analysis and parameter sampling. The procedure consists of a number of steps. Each of these steps might be addressed algorithmically using various computer programs and available software, or manually. We demonstrate our procedure on several models of gene transcription and cell signalling, and show that in many cases we obtain a complete partitioning of the parameter space with respect to multistationarity.
引用
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页数:25
相关论文
共 63 条
[1]   A Petri net approach to the study of persistence in chemical reaction networks [J].
Angeli, David ;
De Leenheer, Patrick ;
Sontag, Eduardo D. .
MATHEMATICAL BIOSCIENCES, 2007, 210 (02) :598-618
[2]  
[Anonymous], 1990, An introduction to nonlinear analysis
[3]   Graph-theoretic criteria for injectivity and unique equilibria in general chemical reaction systems [J].
Banaji, Murad ;
Craciun, Gheorghe .
ADVANCES IN APPLIED MATHEMATICS, 2010, 44 (02) :168-184
[4]  
Ben-Israel A., 1964, J. Math. Anal. Appl, V9, P303, DOI [DOI 10.1016/0022-247X(64)90045-9, 10.1016/0022-247X(64)90045-9]
[5]   Geometry and topology of parameter space: investigating measures of robustness in regulatory networks [J].
Chaves, Madalena ;
Sengupta, Anirvan ;
Sontag, Eduardo D. .
JOURNAL OF MATHEMATICAL BIOLOGY, 2009, 59 (03) :315-358
[6]   Subnetwork analysis reveals dynamic features of complex (bio)chemical networks [J].
Conradi, Carsten ;
Flockerzi, Dietrich ;
Raisch, Jorg ;
Stelling, Jorg .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (49) :19175-19180
[7]   Graph-theoretic analysis of multistationarity using degree theory [J].
Conradi, Carsten ;
Mincheva, Maya .
MATHEMATICS AND COMPUTERS IN SIMULATION, 2017, 133 :76-90
[8]   Catalytic constants enable the emergence of bistability in dual phosphorylation [J].
Conradi, Carsten ;
Mincheva, Maya .
JOURNAL OF THE ROYAL SOCIETY INTERFACE, 2014, 11 (95)
[9]   Multistationarity in mass action networks with applications to ERK activation [J].
Conradi, Carsten ;
Flockerzi, Dietrich .
JOURNAL OF MATHEMATICAL BIOLOGY, 2012, 65 (01) :107-156
[10]   Switching in Mass Action Networks Based on Linear Inequalities [J].
Conradi, Carsten ;
Flockerzi, Dietrich .
SIAM JOURNAL ON APPLIED DYNAMICAL SYSTEMS, 2012, 11 (01) :110-134