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Identifying Kinetic Constants by the Intrinsic Properties of Markov Chain

机译:通过马尔可夫链的本质属性识别动力学常数。

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The process underlying the opening and closing of ion channels in biological can be modelled kinetically as a time-homogeneous Markov chain. How to identify the kinetic constants (transition rates) that measure the 'speed' to jump from one state to another plays a very important role in ion channels. Maximum likelihood method is widely employed for estimating the kinetic constants. However it leads to the non-identifiability since the joint probability distributions could be the same to models with different generator matrices, and the estimation could be very rough since it involves the estimating of some latent variables. Here we develop a totally different approach to supply a gap. Our algorithms employ the intrinsic properties of the Markov process and all calculations are simply reduced to the estimation of their PDFs (probability density functions) of lifetime and death-time of observable states. Once we have them, all subsequent calculations are then automatic and exact. In the current paper, four classical mechanisms: star-graph, line,star-graph branch and (reversible) cyclic chain, are considered to single-ion channels. It is found that all kinetic constants are uniquely determined by the PDFs of their lifetime and death-time for partially (a few) observable states. Numerical examples are included to demonstrate the application of our approach to data.
机译:生物学中离子通道打开和关闭的过程可以动力学建模为时间均质的马尔可夫链。如何识别测量“速度”从一种状态跃迁到另一种状态的动力学常数(转变速率)在离子通道中起着非常重要的作用。最大似然法被广泛用于估计动力学常数。但是,由于联合概率分布对于具有不同生成器矩阵的模型可能是相同的,因此它导致了不可识别性,并且由于涉及一些潜在变量的估计,因此估计可能非常粗糙。在这里,我们开发了一种完全不同的方法来弥补差距。我们的算法利用了马尔可夫过程的内在特性,所有计算都简化为对可观察状态的寿命和死亡时间的PDF(概率密度函数)的估计。一旦有了它们,所有随后的计算都将是自动且精确的。在本文中,单离子通道被认为是四个经典机制:星图,线,星图分支和(可逆)循环链。已发现,对于部分(少数)可观察状态,所有动力学常数均由其寿命和死亡时间的PDF唯一确定。包含了一些数字示例,以演示我们的数据方法的应用。

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