Unsupervised Spatially Embedded Deep Representation of Spatial Transcriptomics

TLDR

Spatial transcriptomics enables dissection of tissue heterogeneity and mapping of inter‑cellular communication, but optimal integration of transcriptomic and spatial data is essential to fully exploit these datasets. This study introduces SEDR, an unsupervised spatially embedded deep representation that jointly models transcriptomic and spatial information. SEDR constructs a low‑dimensional latent representation of gene expression with a deep autoencoder and embeds it with spatial coordinates via a variational graph autoencoder. When applied to human dorsolateral prefrontal cortex data, SEDR improved clustering accuracy, accurately reconstructed prenatal cortical development trajectories, and proved effective for batch integration; on breast cancer data it uncovered heterogeneous tumor sub‑regions, revealing a pro‑inflammatory core and an outer macrophage‑rich ring that promotes immune suppression.

Abstract

Abstract Spatial transcriptomics enable us to dissect tissue heterogeneity and map out inter-cellular communications. Optimal integration of transcriptomics data and associated spatial information is essential towards fully exploiting the data. We present SEDR, an unsupervised spatially embedded deep representation of both transcript and spatial information. The SEDR pipeline uses a deep autoencoder to construct a low-dimensional latent representation of gene expression, which is then simultaneously embedded with the corresponding spatial information through a variational graph autoencoder. We applied SEDR on human dorsolateral prefrontal cortex data and achieved better clustering accuracy, and correctly retraced the prenatal cortex development order with trajectory analysis. We also found the SEDR representation to be eminently suited for batch integration. Applying SEDR to human breast cancer data, we discerned heterogeneous sub-regions within a visually homogenous tumor region, identifying a tumor core with pro-inflammatory microenvironment and an outer ring region enriched with tumor associated macrophages which drives an immune suppressive microenvironment.