SpatialESD: Spatial Ensemble Domain Detection in Spatial Transcriptomics

ABSTRACT Spatial transcriptomics (ST) measures gene expression while preserving spatial context within tissues. One of the key tasks in ST analysis is spatial domain detection, which remains challenging due to the complex structure of ST data and the varying performance of individual clustering methods. To address this, we propose SpatialESD, a Spatial EnSemble Domain detection method that integrates results from different spatial domain detection methods to improve spatial domain detection. SpatialESD captures both direct cooccurrence patterns and multiscale indirect relationships between clusters, improving the robustness and accuracy of spatial domain detection. We evaluated SpatialESD on simulated datasets and multiple 10x Visium spatial transcriptomics datasets, including human brain, breast cancer, and ovarian cancer samples. The results show that SpatialESD consistently outperforms individual methods and the existing EnSDD ensemble method in terms of clustering accuracy and stability. Based on the identified domains, we further detected domain‐specific differentially expressed genes and performed trajectory and cell–cell interaction analyses. These results reveal spatial patterns of gene expression and cellular communication, offering insights into tissue organization and disease mechanisms. Overall, SpatialESD provides a reliable and effective solution for spatial domain detection in ST data and facilitates downstream biological discovery.