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活细胞中粒子轨迹的统计分析。

Statistical analysis of particle trajectories in living cells.

作者信息

Briane Vincent, Kervrann Charles, Vimond Myriam

机构信息

Inria Rennes, Serpico Project Team, Campus Universitaire de Beaulieu, 35042 Rennes Cedex, France.

CREST, Ensai, Université Bretagne Loire, Rue Blaise Pascal, 35172 Bruz, France.

出版信息

Phys Rev E. 2018 Jun;97(6-1):062121. doi: 10.1103/PhysRevE.97.062121.

DOI:10.1103/PhysRevE.97.062121
PMID:30011544
Abstract

Recent advances in molecular biology and fluorescence microscopy imaging have made possible the inference of the dynamics of molecules in living cells. Such inference allows us to understand and determine the organization and function of the cell. The trajectories of particles (e.g., biomolecules) in living cells, computed with the help of object tracking methods, can be modeled with diffusion processes. Three types of diffusion are considered: (i) free diffusion, (ii) subdiffusion, and (iii) superdiffusion. The mean-square displacement (MSD) is generally used to discriminate the three types of particle dynamics. We propose here a nonparametric three-decision test as an alternative to the MSD method. The rejection of the null hypothesis, i.e., free diffusion, is accompanied by claims of the direction of the alternative (subdiffusion or superdiffusion). We study the asymptotic behavior of the test statistic under the null hypothesis and under parametric alternatives which are currently considered in the biophysics literature. In addition, we adapt the multiple-testing procedure of Benjamini and Hochberg to fit with the three-decision-test setting, in order to apply the test procedure to a collection of independent trajectories. The performance of our procedure is much better than the MSD method as confirmed by Monte Carlo experiments. The method is demonstrated on real data sets corresponding to protein dynamics observed in fluorescence microscopy.

摘要

分子生物学和荧光显微镜成像技术的最新进展使得推断活细胞中分子的动力学成为可能。这种推断使我们能够理解和确定细胞的组织与功能。借助目标跟踪方法计算出的活细胞中粒子(如生物分子)的轨迹,可以用扩散过程进行建模。考虑三种类型的扩散:(i)自由扩散,(ii)次扩散,以及(iii)超扩散。均方位移(MSD)通常用于区分这三种类型的粒子动力学。我们在此提出一种非参数三决策检验,作为MSD方法的替代方法。原假设(即自由扩散)的拒绝伴随着对备择假设方向(次扩散或超扩散)的断言。我们研究了原假设下以及生物物理文献中当前考虑的参数备择假设下检验统计量的渐近行为。此外,我们调整了Benjamini和Hochberg的多重检验程序以适应三决策检验设置,以便将检验程序应用于一组独立轨迹。如蒙特卡罗实验所证实的,我们程序的性能比MSD方法要好得多。该方法在与荧光显微镜下观察到的蛋白质动力学相对应的真实数据集上得到了验证。

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