Dimensionality reduction for visualizing spatially resolved profiling data using SpaSNE

Abstract

Background: Spatially resolved profiling technologies to quantify transcriptomes, epigenomes, and proteomes have been emerging as groundbreaking methods for comprehensive molecular characterizations. Dimensionality reduction and visualization is an essential step to analyze and interpret spatially resolved profiling data. However, state-of-the-art dimensionality reduction methods for single-cell sequencing data, such as the t-distributed stochastic neighbor embedding (t-SNE) and uniform manifold approximation and projection (UMAP), were not tailored for spatially resolved profiling data. Results: Here we developed a spatially resolved t-SNE (SpaSNE) method to integrate both spatial and molecular information. We applied it to a variety of public spatially resolved profiling datasets that were generated from 3 experimental platforms and consisted of cells from different diseases, tissues, and cell types. To compare the performances of SpaSNE, t-SNE, and UMAP, we applied them to 4 spatially resolved profiling datasets obtained from 3 distinct experimental platforms (Visium, STARmap, and MERFISH) on both diseased and normal tissues. Comparisons between SpaSNE and these state-of-the-art approaches reveal that SpaSNE achieves more accurate and meaningful visualization that better elucidates the underlying spatial and molecular data structures. Conclusions: This work demonstrates the broad application of SpaSNE for reliable and robust interpretation of cell types based on both molecular and spatial information, which can set the foundation for many subsequent analysis steps, such as differential gene expression and trajectory or pseudotime analysis on the spatially resolved profiling data.