Deterministic characterization of phase noise in biomolecular oscillators
Deterministic characterization of phase noise in biomolecular oscillators
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DOI：
10.1088/1478-3975/8/5/055008
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发表时间：
2011-10-01
期刊：
影响因子：
2
通讯作者：
Mehrotra, A.
中科院分区：
文献类型：
--
作者：
Koeppl, H.;Hafner, M.;Mehrotra, A.
除了许多外部扰动之外，由于化学动力学的随机性，细胞振荡器还面临着内在的扰动。生物分子振荡器的参数集不同或结构不同，对这种内在扰动表现出不同的弹性。可以通过集合随机模拟来评估这种弹性。这些计算成本高昂，并且不允许进一步深入了解所观察到的弹性的机械原因。对于稳定状态下运行的反应系统，可以使用线性噪声近似 (LNA) 来确定分子噪声的影响。在这里，我们表明基于 LNA 的方法对于振荡系统失败，并且我们提出了替代方案。它产生随机振荡器的相位扩散系数的渐近表达式。此外，它使我们能够找出振荡系统中每个反应的噪声贡献。我们在果蝇生物钟的单环模型上测试了该方法。我们的结果与通过随机模拟获得的结果一致，计算效率提高了大约三个数量级。
On top of the many external perturbations, cellular oscillators also face intrinsic perturbations due the randomness of chemical kinetics. Biomolecular oscillators, distinct in their parameter sets or distinct in their architecture, show different resilience with respect to such intrinsic perturbations. Assessing this resilience can be done by ensemble stochastic simulations. These are computationally costly and do not permit further insights into the mechanistic cause of the observed resilience. For reaction systems operating at a steady state, the linear noise approximation (LNA) can be used to determine the effect of molecular noise. Here we show that methods based on LNA fail for oscillatory systems and we propose an alternative ansatz. It yields an asymptotic expression for the phase diffusion coefficient of stochastic oscillators. Moreover, it allows us to single out the noise contribution of every reaction in an oscillatory system. We test the approach on the one-loop model of the Drosophila circadian clock. Our results are consistent with those obtained through stochastic simulations with a gain in computational efficiency of about three orders of magnitude.