Spatial domains identification in spatial transcriptomics by domain knowledge-aware and subspace-enhanced graph contrastive learning

Spatial transcriptomics (ST) technologies have emerged as an effective tool to identify the spatial architecture of the tissue, facilitating a comprehensive understanding of organ function and 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. To this end, we propose a graph contrastive learning framework, GRAS4T, which combines contrastive learning and subspace module to accurately distinguish different spatial domains by capturing 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 images prior, preserving information crucial for the clustering task. Experimental results on 8 ST datasets from 5 different platforms show that GRAS4T outperforms five state-of-the-art competing methods in spatial domain identification. 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.