Luke Braithwaite | Searcharxiv

arXiv2025

Topotein: Topological Deep Learning for Protein Representation Learning

Protein representation learning (PRL) is crucial for understanding structure-function relationships, yet current sequence- and graph-based methods fail to capture the hierarchical organization inherent in protein structures. We introduce Topotein, a comprehensive framework that applies topological deep learning to PRL through the novel Protein Combinatorial Complex (PCC) and Topology-Complete Perceptron Network (TCPNet). Our PCC represents proteins at multiple hierarchical levels -- from residues to secondary structures to complete proteins -- while preserving geometric information at each level. TCPNet employs SE(3)-equivariant message passing across these hierarchical structures, enabling more effective capture of multi-scale structural patterns. Through extensive experiments on four PRL tasks, TCPNet consistently outperforms state-of-the-art geometric graph neural networks. Our approach demonstrates particular strength in tasks such as fold classification which require understanding of secondary structure arrangements, validating the importance of hierarchical topological features for protein analysis.

cs.LG↗

arXiv2024

Heterogeneous Sheaf Neural Networks

Heterogeneous graphs, whose nodes and edges can belong to different types and feature spaces, arise in many real-world domains, including biology, recommendation, social networks, and computer systems. Existing heterogeneous graph neural networks typically handle this heterogeneity at the architectural level through relation-specific modules, meta-path machinery or type-aware attention, which often leads to increasingly specialised parameter-heavy designs. In this work, we propose HetSheaf, a framework for learning heterogeneous graphs through cellular sheaves. Instead of encoding heterogeneity solely in the architecture, HetSheaf represents it directly in the underlying data structure by assigning type-aware local feature spaces and learning restriction maps conditioned on node features, node types, and edge types. To support graph-level prediction, we further introduce SheafPool, a universal stalk-space readout that aggregates node representations while being invariant to local changes of basis, thereby making graph classification with sheaf networks well-defined and achieving an F1 Score up to 42 percentage points higher than mean pooling. Across a diverse suite of benchmarks (node classification, link prediction and graph classification). HetSheaf consistently achieves up to 2 percentage points higher performance (up to 94.97% Macro F1 Score on node classification and up to 99.62% on link prediction) on the Heterogeneous Graph Benchmark (HGB) framework against homogeneous (GCN, GAT, GIN, GraphSAGE), heterogeneous (R-GCN, HAT, HGT) and type-agnostic sheaf baselines, while reducing the number of parameters by up to 10$\times$.

cs.LG↗