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Topological Data Analysis of Spatial Patterning in Heterogeneous Cell Populations: Clustering and Sorting With Varying Cell-Cell Adhesion
Dhananjay Bhaskar, William Y. Zhang, Alexandria Volkening, Björn Sandstede, Ian Y. Wong
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.
From Topological Analyses to Functional Modeling: The Case of Hippocampus
Topological data analyses are widely used for describing and conceptualizing large volumes of neurobiological data, e.g., for quantifying spiking outputs of large neuronal ensembles and thus understanding the functions of the corresponding networks. Below we discuss an approach in which convergent topological analyses produce insights into how information may be processed in mammalian hippocampus—a brain part that plays a key role in learning and memory. The resulting functional model provides a unifying framework for integrating spiking data at different timescales and following the course of spatial learning at different levels of spatiotemporal granularity. This approach allows accounting for contributions from various physiological phenomena into spatial cognition—the neuronal spiking statistics, the effects of spiking synchronization by different brain waves, the roles played by synaptic efficacies and so forth. In particular, it is possible to demonstrate that networks with plastic and transient synaptic architectures can encode stable cognitive maps, revealing the characteristic timescales of memory processing.