Statistical method for comparing the level of intracellular organization between cells
Statistical method for comparing the level of intracellular organization between cells
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DOI：
10.1073/pnas.1212277109
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发表时间：
2013-03-12
影响因子：
11.1
通讯作者：
Marshall, Wallace F.
中科院分区：
文献类型：
--
作者：
Apte, Zachary S.;Marshall, Wallace F.
分析复杂涌现行为的系统级方法需要对微观和宏观尺度上的行为变化进行定量表征。在这里，我们考虑的问题，细胞的组织和描述的统计方法，定量比较不同群体的类似的物理对象，如细胞之间的内部组织。这种比较是通过几个分析步骤来实现的。从细胞的三维或二维图像开始，对图像进行分割以识别单个细胞。记录内部感兴趣点的位置，例如细胞器或蛋白质。为了定义每个单元中的内部点的配置，对各个单元进行有界Voronoi细分：将单元的有界体积或区域细分为由内部感兴趣点的位置确定的子体积。一种统计方法被应用于产生一个度量的相似性程度的人口之间的组织。我们应用这种方法来测试中心粒是否在全球细胞组织中发挥作用，使用突变体的绿色衣藻莱因哈德与已知的改变中心粒的数量，结构和位置作为模型系统。比较突变群体和野生型群体揭示了突变株的组织程度的显着差异。这些计算和实验结果为先前的观察研究提供了统计支持，并支持中心粒在产生或维持全球细胞组织中发挥作用的观点。我们的研究结果证实，这种方法可以用来灵敏地比较细胞内组织的程度和类型。
Systems level approaches to analyzing complex emergent behavior require quantitative characterization of alterations of behavior on both the microscale and macroscale. Here we consider the problem of cellular organization and describe a statistical methodology for quantitative comparison of the internal organization between different populations of similar physical objects, such as cells. This comparison is achieved with several steps of analysis. Starting with three-dimensional or two-dimensional images of cells, images are segmented to identify individual cells. Locations of internal points of interest, such as organelles or proteins, are recorded. To define the configuration of internal points in each cell, the individual cells are subjected to bounded Voronoi tessellation: subdividing the bounded volume or area of the cell into subvolumes determined by the locations of the internal points of interest. A statistical methodology is applied to yield a metric for similarity in degree of organization between populations. We applied this methodology to test whether centrioles play a role in global cellular organization, using mutants of the green alga Chlamydomonas reinhardtii with known alterations in centriole number, structure, and position as a model system. Comparing mutant populations and wild-type populations revealed a dramatic difference in the degree of organization in the mutant strains. These computational and experimental results provide statistical support for prior observational studies and support the idea that centrioles play a role in generating or maintaining global cellular organization. Our results confirm that this method can be used to sensitively compare the extent and type of organization within cells.