Representing perturbed dynamics in biological network models.
We study the dynamics of gene activities in relatively small size biological networks (up to a few tens of nodes), e.g., the activities of cell-cycle proteins during the mitotic cell-cycle progression. Using the framework of deterministic discrete dynamical models, we characterize the dynamical modifications in response to structural perturbations in the network connectivities. In particular, we focus on how perturbations affect the set of fixed points and sizes of the basins of attraction. Our approach uses two analytical measures: the basin entropy H and the perturbation size Delta , a quantity that reflects the distance between the set of fixed points of the perturbed network and that of the unperturbed network. Applying our approach to the yeast-cell-cycle network introduced by Li [Proc. Natl. Acad. Sci. U.S.A. 101, 4781 (2004)] provides a low-dimensional and informative fingerprint of network behavior under large classes of perturbations. We identify interactions that are crucial for proper network function, and also pinpoint functionally redundant network connections. Selected perturbations exemplify the breadth of dynamical responses in this cell-cycle model.
Stoll
Gautier
G
NCCR Molecular Oncology, chemin des Boveresses 155, 1066 Epalinges, Switzerland. Gautier.stoll@curie.fr
Rougemont
Jacques
J
Naef
Felix
F
D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000502:physiology*; D003198:Computer Simulation; D005786:Gene Expression Regulation / Q000502:physiology; D007700:Kinetics; D008954:Models, Biological; D015233:Models, Statistical; D012441:Saccharomyces cerevisiae / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D018797:Cell Cycle Proteins; D029701:Saccharomyces cerevisiae Proteins