Reference-Informed Spatial Domain Detection Using Weak Supervision for Spatial Transcriptomics

One of the key objectives in spatial transcriptomics (ST) studies is to map the complex organization and functions of tissues. We introduce GraphScrDom, a reference-informed and weakly supervised contrastive learning model that uniquely integrates expert-provided manual annotations (i.e., scribbles) on spatial grids or histology images with cell type–specific gene expression profiles derived from reference single-cell RNA-seq data to perform tissue segmentation. With only limited scribble annotations, GraphScrDom consistently outperforms existing methods across various ST platforms and at both bulk and single-cell resolutions, as evaluated by six widely used metrics, demonstrating strong generalizability and robustness. Additionally, we have developed an integrative software toolkit that includes an interactive annotation interface and a model training module for spatial domain detection, providing a unified and user-friendly framework to facilitate spatial domain analysis.