论文标题

异质细胞种群中空间图案的拓扑数据分析:聚类和分类带有不同的细胞 - 细胞粘附

Topological Data Analysis of Spatial Patterning in Heterogeneous Cell Populations: Clustering and Sorting with Varying Cell-Cell Adhesion

论文作者

Bhaskar, Dhananjay, Zhang, William Y., Volkening, Alexandria, Sandstede, Björn, Wong, Ian Y.

论文摘要

在动物组织形成过程中,不同的细胞类型聚集并分类为分层体系结构。由此产生的空间组织(部分)取决于一种细胞类型与其他细胞类型的粘附强度。但是,这些多细胞空间模式的自动和无监督分类仍然具有挑战性,尤其是考虑到它们的结构多样性和生物学变异性。基于拓扑数据分析的最新发展很有趣,可以揭示组织结构的相似性,但是这些方法在计算上仍然很昂贵。在本文中,我们表明,可以通过持久图像有效地表示从两种相互作用的细胞类型组织的多细胞模式。我们通过自动编码器降低维数的优化组合,结合了层次聚类,可实现高分类的精度,用于具有恒定单元格数的模拟。我们进一步证明,可以将持久性图像标准化以改善由于增殖而导致细胞数量变化的模拟分类。最后,我们系统地考虑合并不同拓扑特征以及有关每种细胞类型的信息以提高分类准确性的重要性。我们设想,基于持久图像的拓扑机器学习将使发育和疾病中发生的复杂组织体系结构的多功能和稳健分类。

Different cell types aggregate and sort into hierarchical architectures during the formation of animal tissues. The resulting spatial organization depends (in part) on the strength of adhesion of one cell type to itself relative to other cell types. However, automated and unsupervised classification of these multicellular spatial patterns remains challenging, particularly given their structural diversity and biological variability. Recent developments based on topological data analysis are intriguing to reveal similarities in tissue architecture, but these methods remain computationally expensive. In this article, we show that multicellular patterns organized from two interacting cell types can be efficiently represented through persistence images. Our optimized combination of dimensionality reduction via autoencoders, combined with hierarchical clustering, achieved high classification accuracy for simulations with constant cell numbers. We further demonstrate that persistence images can be normalized to improve classification for simulations with varying cell numbers due to proliferation. Finally, we systematically consider the importance of incorporating different topological features as well as information about each cell type to improve classification accuracy. We envision that topological machine learning based on persistence images will enable versatile and robust classification of complex tissue architectures that occur in development and disease.

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