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Noise in Gene Regulatory Networks

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4 Author(s)
Lestas, I. ; Cambridge Univ., Cambridge ; Paulsson, J. ; Ross, N.E. ; Vinnicombe, G.

Life processes in single cells and at the molecular level are inherently stochastic. Quantifying the noise is, however, far from trivial, as a major contribution comes from intrinsic fluctuations, arising from the randomness in the times between discrete jumps. It is shown in this paper how a noise-filtering setup with an operator theoretic interpretation can be relevant for analyzing the intrinsic stochasticity in jump processes described by master equations. Such interpretation naturally exists in linear noise approximations, but it also provides an exact description of the jump process when the transition rates are linear. As an important example, it is shown in this paper how, by addressing the proximity of the underlying dynamics in an appropriate topology, a sequence of coupled birth-death processes, which can be relevant in gene expression, tends to a pure delay; this implies important limitations in noise suppression capabilities. Despite the exactness, in a linear regime, of the analysis of noise in conjunction with the network dynamics, we emphasize in this paper the importance of also analyzing dynamic behavior when transition rates are highly nonlinear; otherwise, steady-state solutions can be misinterpreted. The examples are taken from systems with macroscopic models leading to bistability. It is discussed that bistability in the deterministic mass action kinetics and bimodality in the steady-state solution of the master equation neither always imply one another nor do they necessarily lead to efficient switching behaviours: the underlying dynamics need to be taken into account. Finally, we explore some of these issues in relation to a model of the lac operation.

Published in:

Automatic Control, IEEE Transactions on  (Volume:53 ,  Issue: Special Issue )