GREmLN: A Cellular Graph Structure Aware Transcriptomics Foundation Model

The ever-increasing availability of large-scale single-cell profiles presents an opportunity to develop foundation models to capture cell properties and behavior. However, standard language models such as transformers benefit from sequentially structured data with well defined absolute or relative positional relationships, while single cell RNA data have orderless gene features. Molecular-interaction graphs, such as protein-protein interaction (PPI) networks or gene regulatory networks (GRN), offer graph structure-based models that effectively encode both non-local gene token dependencies, as well as potential causal relationships. We introduce GREmLN (Gene Regulatory Embedding-based Large Neural model), a foundation model that leverages graph signal processing to embed gene token graph structure directly within its attention mechanism, producing biologically informed single cell specific gene embeddings. Our model faithfully captures transcriptomic landscapes and achieves superior performance relative to state-of-the-art baselines on cell type annotation, graph structure understanding, and fine-tuned reverse perturbation prediction tasks. It offers a unified and interpretable framework for learning high-capacity foundational representations that capture complex long-range regulatory dependencies from high-dimensional single-cell transcriptomic data. The quality of network inference is not a focus of this study. Our framework applies to all graph-structured priors.