Reliable prediction of short linear motifs in the human proteome

Short linear motifs (SLiMs) are small interaction modules within intrinsically disordered regions of proteins that interact with specific domains, and thereby regulate numerous biological processes. Their limited sequence information leads to frequent false positive hits in computational and experimental SLiM identification methods. We present SLiMMine, a deep learning-based method to identify SLiMs in the human proteome. By refining the annotations of known motif classes, we created a high-quality training dataset. Using protein embeddings and neural networks, SLiMMine reliably predicts novel SLiM candidates in known classes, eliminates ~80% of the pattern matching-based hits as false-positives, furthermore, it also functions as a discovery tool to find uncharacterized SLiMs based on optimal sequence environment. Finally, narrowing the broad interactor-domain definitions of known SLiM classes to specific human proteins enables more precise linking of predicted SLiMs to known protein-protein interactions. SLiMMine is available as a user-friendly, multipurpose web server at https://slimmine.pbrg.hu/ .