Orlando David A, Iversen Edwin S, Hartemink Alexander J, Haase Steven B
Program in Computational Biology & Bioinformatics, 102 North Building, Box 90090, Duke University, Durham, North Carolina 27708, USA,
Ann Appl Stat. 2009 Winter;3(4):1521-1541. doi: 10.1214/09-AOAS264.
We present a flexible branching process model for cell population dynamics in synchrony/time-series experiments used to study important cellular processes. Its formulation is constructive, based on an accounting of the unique cohorts in the population as they arise and evolve over time, allowing it to be written in closed form. The model can attribute effects to subsets of the population, providing flexibility not available using the models historically applied to these populations. It provides a tool for in silico synchronization of the population and can be used to deconvolve population-level experimental measurements, such as temporal expression profiles. It also allows for the direct comparison of assay measurements made from multiple experiments. The model can be fit either to budding index or DNA content measurements, or both, and is easily adaptable to new forms of data. The ability to use DNA content data makes the model applicable to almost any organism. We describe the model and illustrate its utility and flexibility in a study of cell cycle progression in the yeast Saccharomyces cerevisiae.
我们提出了一种灵活的分支过程模型,用于在用于研究重要细胞过程的同步/时间序列实验中的细胞群体动态。它的公式是建设性的,基于对群体中独特队列随时间出现和演变的核算,使其能够以封闭形式写出。该模型可以将效应归因于群体的子集,提供了使用历史上应用于这些群体的模型所没有的灵活性。它提供了一种在计算机上对群体进行同步的工具,可用于解卷积群体水平的实验测量,如时间表达谱。它还允许直接比较来自多个实验的测定测量。该模型可以拟合到出芽指数或DNA含量测量值,或两者兼而有之,并且很容易适应新的数据形式。使用DNA含量数据的能力使该模型几乎适用于任何生物体。我们描述了该模型,并在酿酒酵母细胞周期进程的研究中说明了其效用和灵活性。