Quantifying Robustness of Yeast Cell Cycle Network: The Funneled Energy Landscape Perspectives

¹ State University of New York at Stony Brook

^* To whom correspondence should be addressed. E-mail: jin.wang.1{at}stonybrook.edu.

Submitted on August 4, 2006
Revised on September 21, 2006
Accepted on 12 December 2006

	Abstract

We study the origin of robustness of yeast cell cycle cellular network through uncovering its underlying energy landscape. This is realized from the information of the steady steady probabilities by solving a discrete set of kinetic master equations for the network. We discovered that the potential landscape of yeast cell cycle network is funnelled towards the global minimum, G1 state. The ratio of the energy gap between G1 and average versus roughness of the landscape termed as robustness ratio (RR) becomes a quantitative measure of the robustness and stability for the network. The funnelled landscape is quite robust against random perturbations from the inherent wiring or connections of the network. There exists a global phase transition between the more sensitive response or less self degradation phase leading to underlying funneled global landscape with large RR, and insensitive response or more self degradation phase leading to shallower underlying landscape of the network with small RR. Furthermore, we show the more robust landscape also leads to less dissipation cost of the network. Funnelled landscape is a realization of Darwinian principle of natural selection at cellular network level. It provides an optimal criterion for network wiring connections and design.

Key Words: Cell Cycle Cellular Network, Energy Landscape, Funnel, Network Design, Robustness

This article has been cited by other articles:

				J. Wang, L. Xu, and E. Wang Potential landscape and flux framework of nonequilibrium networks: Robustness, dissipation, and coherence of biochemical oscillations PNAS, August 26, 2008; 105(34): 12271 - 12276. [Abstract] [Full Text] [PDF]

				S. Lapidus, B. Han, and J. Wang Intrinsic noise, dissipation cost, and robustness of cellular networks: The underlying energy landscape of MAPK signal transduction PNAS, April 22, 2008; 105(16): 6039 - 6044. [Abstract] [Full Text] [PDF]