拴系粒子实验中DNA成环动力学的扩散隐马尔可夫模型表征
Diffusive hidden Markov model characterization of DNA looping dynamics in tethered particle experiments
摘要：
在许多生物化学过程中，蛋白质在远处与DNA结合，通过底层DNA中的环紧密结合。例如，一些基因调控蛋白的功能依赖于这种DNA环相互作用。我们提出了一种新的技术，用于表征在体外循环形成的动力学，观察使用拴系粒子的方法，并将其应用于循环由λ阻遏物诱导的实验数据。我们的方法使用修改后的（扩散）隐马尔可夫分析，直接结合所观察到的拴系珠的布朗运动。我们将使用我们的方法发现的循环寿命（我们发现在一定范围的采样频率上是一致的）与通过传统的阈值交叉分析获得的循环寿命进行比较（这可能取决于原始数据在时域中的过滤方式）。我们的方法不涉及任何时间过滤，可以检测循环行为的突然变化。例如，我们展示了我们的方法如何识别长寿命的、动力学上不同的状态之间的转换，否则这些状态很难识别。
英文摘要：
In many biochemical processes, proteins bound to DNA at distant sites are brought into close proximity by loops in the underlying DNA. For example, the function of some gene-regulatory proteins depends on such DNA looping interactions. We present a new technique for characterizing the kinetics of loop formation in vitro, as observed using the tethered particle method, and apply it to experimental data on looping induced by lambda repressor. Our method uses a modified (diffusive) hidden Markov analysis that directly incorporates the Brownian motion of the observed tethered bead. We compare looping lifetimes found with our method (which we find are consistent over a range of sampling frequencies) to those obtained via the traditional threshold-crossing analysis (which can vary depending on how the raw data are filtered in the time domain). Our method does not involve any time filtering and can detect sudden changes in looping behavior. For example, we show how our method can identify transitions between long-lived, kinetically distinct states that would otherwise be difficult to discern.
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