Noise can induce bimodality

Although this method can visually amplify the bimodal distribution as the conventional log scale representation does, it was confirmed via personal communication that the bimodality robustly appears in the wide range of input doses 0.

Second, we consider cell-to-cell variability in the activation threshold. Figure 2a-c shows that unimodal distributions were obtained in a log-scale of x. For the same distributions in x, we introduced cell-to-cell variability in the activation threshold following a normal distribution Figure 2d , resulting in bimodal distributions in y Figure 2f.

When shown in a linear scale, some bimodal distributions still persisted for example, the red line in Figure 2f ; graph not shown. Variability in the activation threshold enhances bimodality in the output signal y. The simulation details are exactly the same except that the sample size was 10 4 and, for the Gamma distribution, the value of a was refer to Figure 1 legend. The variability in the activation threshold and the saturation level was generated from normal distributions.

From these simulations, we can conclude that the variability in the input signal and the activation threshold both individually enhanced bimodality in the output signal.

If the input signal and the threshold can be assumed to fluctuate independently due to the fact that they can be processed through sufficiently different biological systems, then the presence of the variability in both will enhance the bimodality further.

Finally, we can consider the variability in the saturation levels of the response curves. Thus, the variability in the saturation level did not have any significant effect on bimodality. The lesson from this work, and one that we see more and more often, is that the interaction of noise and the underlying deterministic dynamics can result in non-intuitive behavior. We are only beginning to understand how noise is exploited by nature [ 4 ] and furthermore by system designers like synthetic biologists [ 5 ], but the influence of noise is likely to be subtle and counter-intuitive to our normal deterministic view of the world.

BMC Syst Biol. PLoS Comp Biol. Download references. You can also search for this author in PubMed Google Scholar. Correspondence to Kyung Hyuk Kim.

This article is published under license to BioMed Central Ltd. Reprints and Permissions. Kim, K. In search of noise-induced bimodality. BMC Biol 10, 89 Download citation. Received : 20 September Accepted : 06 November Published : 07 November Noise induced bimodality in genetic circuits with monostable positive feedback Abstract: The expression of individual genes can be maintained through positive feedback loop mechanisms. If genes are expressed in bursts, then feedback either affects the frequency with which bursts occur or their size.

Here we use a tractable hybrid modelling framework to evaluate how noncooperative positive feedback in burst frequency or burst size impacts the protein-level distribution. We confirm the results of previous studies that noncooperative positive feedback in burst frequency can support bimodal distributions. Intriguingly, bimodal distributions are unavailable in the case of feedback in burst size in the hybrid framework. For more information, access www. AAAS, founded in , has evolved into the world's largest multidisciplinary scientific society with nearly , members and subscribers.

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