Analysis of single-molecule FRET trajectories using hidden Markov modeling
Analysis of single-molecule FRET trajectories using hidden Markov modeling
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DOI：
10.1529/biophysj.106.082487
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发表时间：
2006-09-01
影响因子：
3.4
通讯作者：
Ha, Taekjip
中科院分区：
文献类型：
--
作者：
McKinney, Sean A.;Joo, Chirlmin;Ha, Taekjip
单分子荧光共振能量转移（FRET）轨迹的分析已成为一个重要的生物物理学的兴趣。在推导时间分组数据系统的各种状态之间的转换率时，研究人员依赖于简单但通常是任意的方法从FRET轨迹中提取速率。虽然这些方法已被证明是令人满意的情况下，良好的分离，低噪声，两个或三个状态的系统，它们变得不太可靠时，应用到一个系统的更大的复杂性。我们已经开发了一种分析方案，将单分子时间分组FRET轨迹作为隐马尔可夫过程，允许仅基于概率来确定状态的最可能的FRET值分布及其相互转换率，同时确定每个轨迹的基本状态的最可能的时间序列。结合转移密度图和贝叶斯信息准则，我们还可以确定系统中存在的不同状态的数量以及状态到状态的转移概率。在这里，我们提出的算法，并测试其局限性与各种模拟数据和以前报道的霍利迪交界处的数据。然后将该算法应用于DNA构建体上的三个RecA单体的结合和解离的分析。
The analysis of single-molecule fluorescence resonance energy transfer ( FRET) trajectories has become one of significant biophysical interest. In deducing the transition rates between various states of a system for time-binned data, researchers have relied on simple, but often arbitrary methods of extracting rates from FRET trajectories. Although these methods have proven satisfactory in cases of well-separated, low-noise, two-or three-state systems, they become less reliable when applied to a system of greater complexity. We have developed an analysis scheme that casts single- molecule time-binned FRET trajectories as hidden Markov processes, allowing one to determine, based on probability alone, the most likely FRET-value distributions of states and their interconversion rates while simultaneously determining the most likely time sequence of underlying states for each trajectory. Together with a transition density plot and Bayesian information criterion we can also determine the number of different states present in a system in addition to the state-to-state transition probabilities. Here we present the algorithm and test its limitations with various simulated data and previously reported Holliday junction data. The algorithm is then applied to the analysis of the binding and dissociation of three RecA monomers on a DNA construct.