DGAT: A Dual-Graph Attention Network for Inferring Spatial Protein Landscapes from Transcriptomics

Spatial transcriptomics (ST) technologies provide genome-wide mRNA profiles in tissue context but lack direct protein-level measurements, which are critical for interpreting cellular function and microenvironmental organization. We present DGAT (Dual-Graph Attention Network), a deep learning framework that imputes spatial protein expression from transcriptomics-only ST data by learning RNA-protein relationships from spatial CITE-seq datasets. DGAT constructs heterogeneous graphs integrating transcriptomic, proteomic, and spatial information, encoded using graph attention networks. Task-specific decoders reconstruct mRNA and predict protein abundance from a shared latent representation. Benchmarking across public and in-house datasets-including tonsil, breast cancer, glioblastoma, and malignant mesothelioma-demonstrates that DGAT outperforms existing methods in protein imputation accuracy. Applied to ST datasets lacking protein measurements, DGAT reveals spatially distinct cell states, immune phenotypes, and tissue architectures not evident from transcriptomics alone. DGAT enables proteome-level insights from transcriptomics-only data, bridging a critical gap in spatial omics and enhancing functional interpretation in cancer, immunology, and precision medicine.