Bayesian inference for ion-channel gating mechanisms directly from single-channel recordings, using Markov chain Monte Carlo
Bayesian inference for ion-channel gating mechanisms directly from single-channel recordings, using Markov chain Monte Carlo
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DOI：
10.1098/rspa.1999.0432
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发表时间：
1999-08-08
影响因子：
3.5
通讯作者：
O'Hagan, A
中科院分区：
文献类型：
--
作者：
Ball, FG;Cai, Y;O'Hagan, A
单离子通道的门控机制通常由有限状态空间连续时间马尔可夫链建模。膜片钳技术使实验者能够记录流经单离子通道的电流。在实践中，电流被噪声和低通滤波破坏，并且以通常非常短的采样间隔采样。我们提出了一种方法，用于执行贝叶斯推理的参数管理的基础单通道门控机制和记录过程中，直接从这样的单通道记录。我们的程序使用称为马尔可夫链蒙特卡罗，这涉及到构建一个马尔可夫链的平衡分布是由未知参数的后验分布给定的观测数据的技术。然后，对马尔可夫链的模拟使研究人员能够估计所需的后验分布。除了提供一种估计用于对单通道门控机制以及开放和闭合电导水平的平均值和方差进行建模的底层马尔可夫链的转移速率的方法之外，我们的马尔可夫链蒙特卡罗模拟的输出还可以用于估计单通道特性，例如开放和闭合逗留时间的平均长度，并重建未观察到的量子信号，该量子信号指示信道是打开还是关闭。主要从离子通道文献的几个数值例子说明了该理论。
The gating mechanism of a single-ion channel is usually modelled by a finite-state-space continuous-time Markov chain. The patch-clamp technique enables the experimenter to record the current flowing across a single-ion channel. In practice, the current is corrupted by noise and low-pass filtering, and is sampled with a typically very short sampling interval. We present a method for performing Bayesian inference about parameters governing the underlying single-channel gating mechanism and the recording process, directly from such single-channel recordings. Our procedure uses a technique known as Markov chain Monte Carlo, which involves constructing a Markov chain whose equilibrium distribution is given by the posterior distribution of the unknown parameters given the observed data. Simulation of that Markov chain then enables the investigator to estimate the required posterior distribution. As well as providing a method of estimating the transition rates of the underlying Markov chain used to model the single-channel gating mechanism and the means and variances of open and closed conductance levels, the output from our Markov chain Monte Carlo simulations can also be used to estimate single-channel properties, such as the mean lengths of open and closed sojourn times, and to reconstruct the unobserved quantal signal which indicates whether the channel is open or closed. The theory is illustrated by several numerical examples taken mainly from the ion-channel literature.