Spage2vec: Unsupervised representation of localized spatial gene expression signatures

Investigations of spatial cellular composition of tissue architectures revealed by multiplexed in situ RNA detection often rely on inaccurate cell segmentation or prior biological knowledge from complementary single‐cell sequencing experiments. Here, we present spage2vec, an unsupervised segmentation‐free approach for decrypting the spatial transcriptomic heterogeneity of complex tissues at subcellular resolution. Spage2vec represents the spatial transcriptomic landscape of tissue samples as a graph and leverages a powerful machine learning graph representation technique to create a lower dimensional representation of local spatial gene expression. We apply spage2vec to mouse brain data from three different in situ transcriptomic assays and to a spatial gene expression dataset consisting of hundreds of individual cells. We show that learned representations encode meaningful biological spatial information of re‐occurring localized gene expression signatures involved in cellular and subcellular processes. DATABASE: Spatial gene expression data are available in Zenodo database at https://doi.org/10.5281/zenodo.3897401. Source code for reproducing analysis results and figures is available in Zenodo database at http://www.doi.org/10.5281/zenodo.4030404.