Deformation-based nuclear morphometry: Capturing nuclear shape variation in HeLa cells
Deformation-based nuclear morphometry: Capturing nuclear shape variation in HeLa cells
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DOI：
10.1002/cyto.a.20506
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发表时间：
2008-04-01
期刊：
影响因子：
3.7
通讯作者：
Murphy, Robert F.
中科院分区：
文献类型：
--
作者：
Rohde, Gustavo K.;Ribeiro, Alexandre J. S.;Murphy, Robert F.
核形状分布的经验表征是一个重要的未解决的问题，在生物学和医学中有许多应用。许多遗传性疾病和癌症具有核形态的改变，并且用于表征形态的方法可以帮助诊断和基本理解这些疾病。自动化方法已被用于测量与细胞核的大小和形状相关的特征，并且这些特征的统计分析通常假设基本的欧几里得（线性）向量空间来执行。我们讨论的困难与分析的核形状的事实，形状空间是非线性的，并展示方法表征核形状和形状分布的基础上的空间变换，映射一个核到另一个。通过结合大变形度规映射与多维标度，我们提供了一个灵活的方法来阐明核形状分布的内在非线性自由度。更具体地说，我们展示了核形状插值和计算平均核形状的方法。我们还提供了一种方法，用于估计的自由参数的数量，有助于形状，以及可视化最具代表性的形状变化的核分布内的方法。所提出的方法可以完全自动化，是独立的图像的维数，并可以处理复杂的形状。示出了通过分析HeLa细胞的两组图像获得的结果。除了确定在正常的HeLa细胞核的变化模式，核纤层蛋白A/C对核形态的影响进行了定量描述。C 2007国际分析细胞学学会。
The empirical characterization of nuclear shape distributions is an important unsolved problem with many applications in biology and medicine. Numerous genetic diseases and cancers have alterations in nuclear morphology, and methods for characterization of morphology could aid in both diagnoses and fundamental understanding of these disorders. Automated approaches have been used to measure features related to the size and shape of the cell nucleus, and statistical analysis of these features has often been performed assuming an underlying Euclidean (linear) vector space. We discuss the difficulties associated with the analysis of nuclear shape in light of the fact that shape spaces are nonlinear, and demonstrate methods for characterizing nuclear shapes and shape distributions based on spatial transformations that map one nucleus to another. By combining large deformation metric mapping with multidimensional scaling we offer a flexible approach for elucidating the intrinsic nonlinear degrees of freedom of a distribution of nuclear shapes. More specifically, we demonstrate approaches for nuclear shape interpolation and computation of mean nuclear shape. We also provide a method for estimating the number of free parameters that contribute to shape as well as an approach for visualizing most representative shape variations within a distribution of nuclei. The proposed methodology can be completely automated, is independent of the dimensionality of the images, and can handle complex shapes. Results obtained by analyzing two sets of images of HeLa cells are shown. In addition to identifying the modes of variation in normal HeLa nuclei, the effects of lamin A/C on nuclear morphology are quantitatively described. C 2007 international Society for Analytical Cytology.