Predicting peptide-mediated interactions on a genome-wide scale.

We describe a method to predict protein-protein interactions (PPIs) formed between structured domains and short peptide motifs. We take an integrative approach based on consensus patterns of known motifs in databases, structures of domain-motif complexes from the PDB and various sources of non-structural evidence. We combine this set of clues using a Bayesian classifier that reports the likelihood of an interaction and obtain significantly improved prediction performance when compared to individual sources of evidence and to previously reported algorithms. Our Bayesian approach was integrated into PrePPI, a structure-based PPI prediction method that, so far, has been limited to interactions formed between two structured domains. Around 80,000 new domain-motif mediated interactions were predicted, thus enhancing PrePPI's coverage of the human protein interactome.