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Visualizing Spatial Bulk and Single Cell Assays in Anatomical Images

Abstract

Visualizing spatial assay data in anatomical images is vital for understanding biological processes in cell, tissue, and organ organizations. Technologies requiring this functionality include traditional one-at-a-time assays, and bulk and single-cell omics experiments, including transcript, protein and metabolite profiling. To address this need, this Ph.D. project developed the \textit{spatialHeatmap} software environment. As an integrated multipurpose visualization and analysis toolbox, \textit{spatialHeatmap} provides flexible solutions for these needs by allowing users to visualize spatial biological data in adequately formatted anatomical images from public collections or custom images, and extend them with a series of large scale data mining graphics. \textit{spatialHeatmap} colors the spatial features (\textit{e.g.} tissues) annotated in the images according to the quantitative abundance levels of measured biomolecules (\textit{e.g.} mRNAs) using a color key. This core functionality of the package is called a spatial heatmap (SHM) plot. Single-cell data can be co-visualized in composite plots that combine SHMs with embedding plots of high-dimensional data. The resulting spatial context information is essential for gaining insights into the tissue-level organization of single-cell data, or vice versa. Functionalities for integrated visualization of cellular compositions of bulk data with deconvolution algorithms are also included. Alternatively, a new co-clustering method automates the association of unlabeled single-cell data with the corresponding source tissues. Spatially resolved single-cell data from more recently developed spatial sequencing technologies can also be co-visualized with the corresponding anatomical SHMs. Additional core functionalities include large-scale identification of biomolecules with spatially selective abundance patterns, and clusters of biomolecules sharing similar abundance profiles.

\textit{spatialHeatmap} is a new software for visualizing spatial assay data in anatomical images with extensions for large-scale data mining and co-visualization of single-cell data. It integrates many novel functionalities into a generic spatial visualization toolbox that is flexible, extensible, and object-oriented by design. A graphical and a command-line interface are provided to support the needs of both non-expert and computational users, respectively. It is distributed as a free, open-source Bioconductor package (\href{https://bioconductor.org/packages/release/bioc/html/spatialHeatmap.html}{https://bioconductor.org/packages/ spatialHeatmap}) that users can install on personal computers, shared servers, or cloud systems. Because of its rich functionalities and broad applicability, \textit{spatialHeatmap} is expected to be widely adopted by the spatial biology community.

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