Analysis of spliceosome dynamics by maximum likelihood fitting of dwell time distributions
Analysis of spliceosome dynamics by maximum likelihood fitting of dwell time distributions
复制标题
通过驻留时间分布的最大似然拟合分析剪接体动力学
DOI：
10.1016/j.ymeth.2018.11.014
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发表时间：
2019
期刊：
影响因子：
4.8
通讯作者：
Hoskins, Aaron A.
中科院分区：
文献类型：
--
作者：
Kaur, Harpreet;Jamalidinan, Fatemehsadat;Condon, Samson G.F.;Senes, Alessandro;Hoskins, Aaron A.
共定位单分子方法可以提供大量关于生物分子组装的有序性和动力学的信息。这些已被广泛用于体外剪接体组装途径的研究。这些实验的关键是结合时间的测量-多分子相互作用的停留时间或结合事件之间的时间。通过分析数百个这样的时间，已经获得了许多新的见解剪接体组装的动力学途径。结合时间的集合通常绘制为直方图，并且可以使用各种方法拟合动力学模型。在这里，我们描述了使用最大似然方法来拟合驻留时间分布，而无需分箱。此外，我们讨论了几个方面的分析这些分布直方图和陷阱，可以遇到，如果不正确的装箱直方图使用。我们在AGATHA软件包中自动化了停留时间分布的最大似然拟合的几个方面。
Colocalization single-molecule methods can provide a wealth of information concerning the ordering and dynamics of biomolecule assembly. These have been used extensively to study the pathways of spliceosome assemblyin vitro. Key to these experiments is the measurement of binding times—either the dwell times of a multi-molecular interaction or times in between binding events. By analyzing hundreds of these times, many new insights into the kinetic pathways governing spliceosome assembly have been obtained. Collections of binding times are often plotted as histograms and can be fit to kinetic models using a variety of methods. Here, we describe the use of maximum likelihood methods to fit dwell time distributions without binning. In addition, we discuss several aspects of analyzing these distributions with histograms and pitfalls that can be encountered if improperly binned histograms are used. We have automated several aspects of maximum likelihood fitting of dwell time distributions in the AGATHA software package.