Dynamical modeling and analysis of large cellular regulatory networks.

Details

Serval ID
serval:BIB_1548FBB8A842
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Dynamical modeling and analysis of large cellular regulatory networks.
Journal
Chaos
Author(s)
Bérenguier D., Chaouiya C., Monteiro P.T., Naldi A., Remy E., Thieffry D., Tichit L.
ISSN
1089-7682 (Electronic)
ISSN-L
1054-1500
Publication state
Published
Issued date
2013
Volume
23
Number
2
Pages
025114
Language
english
Abstract
The dynamical analysis of large biological regulatory networks requires the development of scalable methods for mathematical modeling. Following the approach initially introduced by Thomas, we formalize the interactions between the components of a network in terms of discrete variables, functions, and parameters. Model simulations result in directed graphs, called state transition graphs. We are particularly interested in reachability properties and asymptotic behaviors, which correspond to terminal strongly connected components (or "attractors") in the state transition graph. A well-known problem is the exponential increase of the size of state transition graphs with the number of network components, in particular when using the biologically realistic asynchronous updating assumption. To address this problem, we have developed several complementary methods enabling the analysis of the behavior of large and complex logical models: (i) the definition of transition priority classes to simplify the dynamics; (ii) a model reduction method preserving essential dynamical properties, (iii) a novel algorithm to compact state transition graphs and directly generate compressed representations, emphasizing relevant transient and asymptotic dynamical properties. The power of an approach combining these different methods is demonstrated by applying them to a recent multilevel logical model for the network controlling CD4+ T helper cell response to antigen presentation and to a dozen cytokines. This model accounts for the differentiation of canonical Th1 and Th2 lymphocytes, as well as of inflammatory Th17 and regulatory T cells, along with many hybrid subtypes. All these methods have been implemented into the software GINsim, which enables the definition, the analysis, and the simulation of logical regulatory graphs.
Pubmed
Web of science
Open Access
Yes
Create date
22/08/2013 10:01
Last modification date
20/08/2019 13:44
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