Jinxia Wang, Yuying Huo, Rui Zhao, Yan Pan, Jianqiang Wu, Han Wang, Xiangyu Li
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 (Spatially Multi-Omics graph contrAstive Learning), 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 from mouse and human 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.