Pre-training with Graph Transformers

Graphs are a central representation in biomedical research, capturing molecular interaction networks, gene regulatory circuits, cell--cell communication maps, and knowledge graphs. Despite their importance, currently there is not a broadly reusable foundation model available for graph analysis comparable to those that have transformed language and vision. Existing graph neural networks are typically trained on a single dataset and learn representations specific only to that graph's node features, topology, and label space, limiting their ability to transfer across domains. This lack of generalization is particularly problematic in biology and medicine, where networks vary substantially across cohorts, assays, and institutions. Here we introduce a graph foundation model designed to learn transferable structural representations that are not specific to specific node identities or feature schemes. Our approach leverages feature-agnostic graph properties, including degree statistics, centrality measures, community structure indicators, and diffusion-based signatures, and encodes them as structural prompts. These prompts are integrated with a message-passing backbone to embed diverse graphs into a shared representation space. The model is pretrained once on heterogeneous graphs and subsequently reused on unseen datasets with minimal adaptation. Across multiple benchmarks, our pretrained model matches or exceeds strong supervised baselines while demonstrating superior zero-shot and few-shot generalization on held-out graphs. On the SagePPI benchmark, supervised fine-tuning of the pretrained backbone achieves a mean ROC-AUC of 95.5%, a gain of 21.8% over the best supervised message-passing baseline. The proposed technique thus provides a unique approach toward reusable, foundation-scale models for graph-structured data in biomedical and network science applications.

Accurate prediction of absorption, distribution, metabolism, and excretion (ADME) properties is critical to drug discovery, but remains challenging because ADME endpoints are noisy, interdependent, and often data-limited. We propose a molecular graph-transformer pretraining framework that combines chemistry-specific self-supervision with contrastive mutual information machine learning (cMIM). Our method encodes molecular graphs into latent variables, reconstructs SMILES strings from the graph-derived latent codes, and augments the contrastive objective with domain-specific self-supervised chemistry tasks. Rather than treating these tasks as auxiliary regularizers with separately tuned loss weights, we formulate reconstruction, contrastive discrimination, and chemistry-specific supervision as unit-weighted log-probability factors in a single probabilistic latent-variable objective. For fine-tuning, we propose a multi-task GNN readout architecture with task-specific multilayer perceptron heads, preserving shared representation learning while mitigating negative transfer and improving the modeling of heterogeneous, nonlinear task relationships. Across Biogen, ExpansionRX, and ChEMBL-MT, the resulting Contrastive KERMT pretraining improves over the KERMT baseline by 7.6%, 9.9%, and 9.5% respectively (averaged over significantly-improved endpoints). Adding ADME-adjacent molecules to the pretraining corpus further improves transfer, and the contrastive component sharpens chemically meaningful latent neighborhoods.

Graph transformers are the state-of-the-art for learning from graph-structured data and are empirically known to avoid several pitfalls of message-passing architectures. However, there is limited theoretical analysis on why these models perform well in practice. In this work, we prove that attention-based architectures have structural benefits over graph convolutional networks in the context of node-level prediction tasks. Specifically, we study the neural network gaussian process limits of graph transformers (GAT, Graphormer, Specformer) with infinite width and infinite heads, and derive the node-level and edge-level kernels across the layers. Our results characterise how the node features and the graph structure propagate through the graph attention layers. As a specific example, we prove that graph transformers structurally preserve community information and maintain discriminative node representations even in deep layers, thereby preventing oversmoothing. We provide empirical evidence on synthetic and real-world graphs that validate our theoretical insights, such as integrating informative priors and positional encoding can improve performance of deep graph transformers.