Uncovering operational interactions in genetic networks using asynchronous Boolean dynamics.
Biological networks of large dimensions, with their diagram of interactions, are often well represented by a Boolean model with a family of logical rules. The state space of a Boolean model is finite, and its asynchronous dynamics are fully described by a transition graph in the state space. In this context, a model reduction method will be developed for identifying the active or operational interactions responsible for a given dynamic behaviour. The first step in this procedure is the decomposition of the asynchronous transition graph into its strongly connected components, to obtain a "reduced" and hierarchically organized graph of transitions. The second step consists of the identification of a partial graph of interactions and a sub-family of logical rules that remain operational in a given region of the state space. This model reduction method and its usefulness are illustrated by an application to a model of programmed cell death. The method identifies two mechanisms used by the cell to respond to death-receptor stimulation and decide between the survival and apoptotic pathways.
Tournier
L
L
INRIA Sophia, COMORE Team, 2004, Route des lucioles, B.P. 93, F-06902 Sophia-Antipolis Cedex, France. laurent.tournier@curie.fr
Chaves
M
M
D000465:Algorithms; D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D003198:Computer Simulation; D053263:Gene Regulatory Networks; D008957:Models, Genetic; D016328:NF-kappa B / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics
D016328:NF-kappa B