Spatial Domains Identification in Spatial Transcriptomics Using Modality-Aware and Subspace-Enhanced Graph Contrastive Learning.

Spatial transcriptomics (ST) technologies have emerged as an effective tool to identify the spatial architecture of tissues, facilitating a comprehensive understanding of organ function and the tissue microenvironment. Spatial domain identification is the first and most critical step in ST data analysis, which requires thoughtful utilization of tissue microenvironment and morphological priors. Here, we propose a graph contrastive learning framework, GRAS4T, which combines contrastive learning and a subspace analysis model to accurately distinguish different spatial domains by capturing the tissue microenvironment through self-expressiveness of spots within the same domain. To uncover the pertinent features for spatial domain identification, GRAS4T employs a graph augmentation based on histological image priors, preserving structural information crucial for the clustering task. Experimental results on eight ST datasets from five different platforms show that GRAS4T outperforms five state-of-the-art competing methods. Significantly, GRAS4T excels at separating distinct tissue structures and unveiling more detailed spatial domains. GRAS4T combines the advantages of subspace analysis and graph representation learning with extensibility, making it an ideal framework for ST domain identification.