DisConST: Deciphering Spatial Domains Using Distribution-aware Contrastive Learning for Spatial Transcriptomics

Spatial transcriptomics (ST) is a cutting-edge technology that provides comprehensive insights into gene expression patterns from a spatial perspective. A key research focus within this field is spatial domain identification, which is essential for exploring tissue organization, biological development, and disease mechanisms. Although methods have been developed, they still face challenges in modeling the gene expression information together with the spatial locations, resulting in suboptimal accuracy. We introduce DisConST (Distribution-aware Contrastive Learning for Spatial Transcriptomics), a novel deep-learning method designed to improve spatial domain detection within spatial transcriptomics datasets. DisConST addresses key challenges, such as the high dropout rates and the complex integration of spatial and gene expression data, by incorporating contrastive learning strategies that are aware of the underlying data distributions. It employs the zero-inflated negative binomial (ZINB) distribution, along with graph contrastive learning, to generate more informative latent representations. These representations efficiently integrate spatial positions, transcriptomic profiles, and cell-type proportions within spots. We validated DisConST across diverse ST datasets of tissues, organs, and embryos from various sequencing platforms in both normal and disease states. Our results consistently demonstrated that DisConST achieves superior spatial domain recognition accuracy compared to existing state-of-the-art methods. Furthermore, our experiments highlighted the utility of DisConST in advancing research on tissue organization, embryonic development, and tumor immune microenvironment dissection. The source code for DisConST is freely available at https://github.com/Zhenpm/DisConST/.