ProtLink is a multispecies heterogeneous graph transformer for protein–protein interaction prediction. The model combines ESM-2 protein sequence embeddings with species-specific PPI context and orthogroup relationships across 516 species, enabling evolutionary information to propagate across species while preserving species-specific interaction structure.

This release uses a 2-layer, 4-head HGT encoder with an MLP link decoder. Protein features are derived from esm2_t33_650m using mean-pooled final-layer residue embeddings. The model is evaluated on human–human PPI prediction, with non-human PPI and protein–orthogroup edges used as graph context.

For the released seed-0 run, ProtLink achieves:

The classification threshold is selected on the validation set by maximizing F1 over the precision–recall curve and is then fixed for test evaluation.

A successful run constructs the exact released HGT + MLP decoder and performs load_state_dict(..., strict=True).

inference.py expects the same heterogeneous graph schema used in training. Save the inference HeteroData object as inference_graph.pt, then run:

The two integers are protein node indices in that graph.

HGT inference is graph-conditioned. The model weights alone do not contain the protein ESM-2 features, PPI context edges, or protein-to-orthogroup membership edges. Those must be reconstructed with the same indexing/schema as training.