JBHI Journal 2026 Journal Article
GraphSTAR: Proximal Operator-Based Graph Neural Network Enhanced by Dynamic Graph Aggregation for Spatial Transcriptomics
- Junyu Li
- Jingquan Yan
- Yi Liao
- Wenxiong Liao
- Ye Liu
- Hongmin Cai
Spatial transcriptomics technologies carry out advanced sequencing analysis of molecular profiles with a spatial context, providing multi-source information essential for elucidating biological regulatory mechanisms. Nonetheless, it poses challenges in the integration of raw spatial coordinates with high-dimensional gene expression profiles in their native feature space. While spatial-aware methods effectively aggregate molecular information from local spatial neighborhoods, they fail to explore the long-range relationships associated with gene expression data. To address this issue, this paper introduces a novel approach termed GraphSTAR that encodes both spatial and gene expression data into undirected graphs, characterizing the local spatial proximity and global transcriptional similarity, respectively. Through a graph aggregation process, GraphSTAR integrates these diverse data sources within a joint graph structure, effectively modeling both local neighborhood relationships and long-range functional associations. Subsequently, a reassembled graph neural network is established by incorporating the graph aggregation into the feed-forward propagation using proximal operators, progressively refining spatial-informed latent representation to decipher spatial expression patterns of genes. Extensive experiments on benchmark datasets demonstrate that GraphSTAR outperforms state-of-the-art methods in both spatial domain identification and cell-type annotation tasks.