Nonlinear dependencies of biochemical reactions for context-specific signaling dynamics.
Sci Rep
; 2: 616, 2012.
Article
en En
| MEDLINE
| ID: mdl-22943002
ABSTRACT
Mathematical modeling can provide unique insights and predictions about a signaling pathway. Parameter variations allow identification of key reactions that govern signaling features such as the response time that may have a direct impact on the functional outcome. The effect of varying one parameter, however, may depend on values of another. To address the issue, we performed multi-parameter variations of an experimentally validated mathematical model of NF-κB regulatory network, and analyzed the inter-relationships of the parameters in shaping key dynamic features. We find that nonlinear dependencies are ubiquitous among parameters. Such phenomena may underlie the emergence of cell type-specific behaviors from essentially the same molecular network. Our results from a multivariate ensemble of models highlight the hypothesis that cell type specificity in signaling phenotype can arise from quantitatively altered strength of reactions in the pathway, in the absence of tissue-specific factors that re-wire the network for a new topology.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Simulación por Computador
/
Transducción de Señal
/
Dinámicas no Lineales
/
Modelos Biológicos
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Sci Rep
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos