SpaMOAL: A spatial multi-omics graph contrastive learning method for spatial domains identification

Abstract Recent advances in spatial multi-omics technologies have opened new avenues for characterizing tissue architecture and function in situ , by simultaneously providing multimodal and complementary information—such as spatially resolved transcriptomic, epigenomic, and proteomic features. Current computational approaches face substantial challenges such as effective integration of multi-omics molecular information with spatial information and corresponding high-resolution histology images. To address this challenge, we proposed SpaMOAL ( Spa tially M ulti- O mics graph contr A stive L earning), a graph-based contrastive learning approach for spatial domain identification. SpaMOAL learns clustering-friendly representations from spatial multi-omics data by integrating spatial coordinates, histological image features and molecular profiles, enabling accurate delineation of spatial tissue domains. Benchmarking across multiple recent paired spatial multi-omics datasets demonstrated that SpaMOAL consistently outperforms existing methods. By enabling accurate spatial domain delineation, SpaMOAL provides a powerful framework for interpreting tissue organization and cellular microenvironments.