LoGoPPI enables fast and accurate protein–protein interaction mapping at scale

Graph-based protein function analysis is powerful, but protein-protein interaction (PPI) networks exist for only a small fraction of animal and plant genomes. We present LoGoPPI, which infers PPIs from sequence by combining bi-encoder global protein representation with local residue-level late interaction. LoGoPPI matches or exceeds state-of-the-art PLM-based cross-encoders while achieving orders-of-magnitude faster inference, up to ∼1,500-fold, and its local branch provides residue-level signals associated with interaction interfaces and structurally flexible regions. This efficiency enables practical proteome-wide PPI reconstruction at scales prohibitive for cross-encoder models, potentially extending interactome mapping to tens of thousands of animal and plant species. LoGoPPI thus provides a scalable framework for comparative and functional analysis of protein networks across diverse taxa.