Noise-induced switches in network systems of the genetic toggle switch

Wang, Junwei; Zhang, Jiajun; Yuan, Zhiwen; Zhou, Tianshou

doi:10.1186/1752-0509-1-50

Cited by 88 publications

(79 citation statements)

References 52 publications

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“…The origin of stochasticity can be attributed to internal and external noises. It is well known that noise can have great impacts on biological systems' dynamical properties (Lipshtat et al 2006;Hasty et al 2000;Vilar et al 2002;Rao et al 2002;Wang et al 2007;Li and Li 2008), for example, noise can induce sustained stochastic oscillation even though the corresponding deterministic system only yields steady state . In this paper, we have also studied the effect of extrinsic noise on the dynamic behavior of the MDNFL.…”

Section: Discussionmentioning

confidence: 99%

“…However, cellular processes at the molecular level are inherently stochastic (Balàsi et al 2011). Numerous studies have revealed the importance of stochastic or probabilistic effects in biological systems where the number of molecules is low enough for noise to be important, and the deterministic chemical kinetic descriptions are limited (Lipshtat et al 2006;Hasty et al 2000;Vilar et al 2002;Rao et al 2002;Wang et al 2007;Li and Li 2008). In addition, noise can also have significant effects on the stability and synchronization of genetic regulatory networks as well as neuronal networks (Shi et al 2008;Wang et al 2009;Guo 2011;Wu et al 2012).…”

Section: Stochastic Model and Noise-induced Dynamics For The Mdnflmentioning

confidence: 99%

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Functional characteristics of a double negative feedback loop mediated by microRNAs

2013

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MicroRNAs (miRNAs) are a class of small, noncoding RNAs that play crucial roles in almost all cellular processes. As key post-transcriptional regulators of gene expression, miRNAs mainly induce mRNA degradation or translational repression. Recently computational and experimental studies have identified an abundance of motifs involving miRNAs and transcriptional factors (TFs). Here, we study the functional characteristics of one such motif, a two-node miRNA-mediated double negative feedback loop (MDNFL) in which a TF suppresses an miRNA and the TF itself is negatively regulated by the miRNA. Several examples of this motif are described from the literature. We propose a general computational model for the MDNFL based on biochemical regulations and explore its dynamics by using bifurcation analysis. Our results show that the MDNFL can behave as a bistable switch. This functional feature is in agreement with experimental observations of the widespread appearance of miRNAs in fate decisions such as differentiation during development. Importantly, it is found that under the interplay of a TF and an miRNA, the MDNFL model can behave as switches for wide ranges of parameters even without cooperative binding of the TF. In addition, we also investigate how extrinsic noise affects dynamic behavior of the MDNFL. Interestingly, it is found that when the MDNFL is in the bistable region, by choosing the appropriate extrinsic noise source, the MDNFL system can switch from one steady state to the other and meanwhile the production of either miRNA or protein is amplified significantly. From an engineering perspective, this noisebased switch and amplifier for gene expression is very easy to control. It is hoped that the results presented here would provide a new insight on how gene expression is regulated by miRNAs and further guidance for experiments.

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Section: Discussionmentioning

confidence: 99%

Section: Stochastic Model and Noise-induced Dynamics For The Mdnflmentioning

confidence: 99%

Functional characteristics of a double negative feedback loop mediated by microRNAs

2013

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“…We can describe this model in the following form [16]: (7) 13 illustrated in Fig. 5 indicates the origin of the bistability [15].…”

Section: The the The The Switching Switching Switching Switching Betwmentioning

confidence: 99%

Parallel logic gates in synthetic gene networks induced by non-Gaussian noise

Jin

Zhang

2013

Phys. Rev. E

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“…However, in the case where small numbers of molecules are present, the modeling assumptions that give rise to the mass action ODE are not valid [11,12,22] and the discrete/stochastic effects captured by the CME should not be ignored. For example, the stochastic version of a bi-stable ODE model can account for switching between "almost stable" states [31,35].…”

Section: Introductionmentioning

confidence: 99%

Switching and Diffusion Models for Gene Regulation Networks

Intep¹,

Higham²,

Mao³

2009

Multiscale Model. Simul.

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We analyze a hierarchy of three regimes for modeling gene regulation. The most complete model is a continuous time, discrete state space, Markov jump process. An intermediate 'switch plus diffusion' model takes the form of a stochastic differential equation driven by an independent continuous time Markov switch. In the third 'switch plus ODE' model the switch remains but the diffusion is removed. The latter two models allow for multi-scale simulation where, for the sake of computational efficiency, system components are treated differently according to their abundance. The 'switch plus ODE' regime was proposed by Paszek (Modeling stochasticity in gene regulation: characterization in the terms of the underlying distribution function, Bulletin of Mathematical Biology, 2007), who analyzed the steady state behavior, showing that the mean was preserved but the variance only approximated that of the full model. Here, we show that the tools of stochastic calculus can be used to analyze first and second moments for all time. A technical issue to be addressed is that the state space for the discrete-valued switch is infinite. We show that the new 'switch plus diffusion' regime preserves the biologically relevant measures of mean and variance, whereas the 'switch plus ODE' model uniformly underestimates the variance in the protein level. We also show that, for biologically relevant parameters, the transient behaviour can differ significantly from the steady state, justifying our time-dependent analysis. Extra computational results are also given for a protein dimerization model that is beyond the scope of the current analysis.

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Noise-induced switches in network systems of the genetic toggle switch

Abstract: Background: Bistability, the capacity to achieve two distinct stable steady states in response to a

Cited by 88 publications

References 52 publications

Functional characteristics of a double negative feedback loop mediated by microRNAs

Functional characteristics of a double negative feedback loop mediated by microRNAs

Parallel logic gates in synthetic gene networks induced by non-Gaussian noise

Switching and Diffusion Models for Gene Regulation Networks

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