Open Access Green as soon as Postprint is submitted to ZB.
Effective parameters determining the information flow in hierarchical biological systems.
Bull. Math. Biol. 73, 706-725 (2011)
Signaling networks are abundant in higher organisms. They play pivotal roles, e.g., during embryonic development or within the immune system. In this contribution, we study the combined effect of the various kinetic parameters on the dynamics of signal transduction. To this end, we consider hierarchical complex systems as prototypes of signaling networks. For given topology, the output of these networks is determined by an interplay of the single parameters. For different kinetics, we describe this by algebraic expressions, the so-called effective parameters.When modeling switch-like interactions by Heaviside step functions, we obtain these effective parameters recursively from the interaction graph. They can be visualized as directed trees, which allows us to easily determine the global effect of single kinetic parameters on the system's behavior. We provide evidence that these results generalize to sigmoidal Hill kinetics.In the case of linear activation functions, we again show that the algebraic expressions can be immediately inferred from the topology of the interaction network. This allows us to transform time-consuming analytic solutions of differential equations into a simple graph-theoretic problem. In this context, we also discuss the impact of our work on parameter estimation problems. An issue is that even the fitting of identifiable effective parameters often turns out to be numerically ill-conditioned. We demonstrate that this fitting problem can be reformulated as the problem of fitting exponential sums, for which robust algorithms exist.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Times Cited
Scopus
Cited By
Cited By
Altmetric
1.873
1.083
2
4
Annotations
Special Publikation
Hide on homepage
Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Effective parameters; Signaling networks; Parameter estimation; Piecewise linear ODEs; Signaling networks
Language
english
Publication Year
2011
Prepublished in Year
2010
HGF-reported in Year
2010
ISSN (print) / ISBN
0092-8240
e-ISSN
1522-9602
Journal
Bulletin of Mathematical Biology
Quellenangaben
Volume: 73,
Issue: 4,
Pages: 706-725
Publisher
Springer
Publishing Place
New York, NY [u.a.)
Reviewing status
Peer reviewed
POF-Topic(s)
30505 - New Technologies for Biomedical Discoveries
Research field(s)
Enabling and Novel Technologies
PSP Element(s)
G-503700-001
PubMed ID
21181504
Scopus ID
79953124142
Erfassungsdatum
2010-12-31