Abstract
Advancements in spatial transcriptomics have transformed our understanding of organ function and tissue microenvironment. However, accurately identifying spatial domains to depict genome heterogeneity and cellular interactions remains a challenge. In this study, we propose EnSDD (Ensemble-learning for Spatial Domain Detection), a method that ingeniously integrates eight state-of-the-art spatial domain detection methods to automatically identify spatial domains. A key innovation of EnSDD is its dynamic weighting mechanism within the ensemble learning process, which optimizes the contribution of each base model and provides a performance evaluation metric without the need for ground truth data. By leveraging the spatial domains identified through EnSDD, we incorporate the detection of domain-specific spatially variable genes and the spatial distribution of cell types, thereby providing deeper insights into tissue heterogeneity. We validate EnSDD across diverse spatial transcriptomics datasets from various tissue organizational structures. Our results demonstrate that EnSDD significantly enhances spatial domain identification accuracy, identifies genes with spatial expression patterns, and reveals domain-specific cell type enrichment patterns, offering invaluable insights into tissue spatial heterogeneity and regionalization.