ProtEx: A Retrieval-Augmented Approach for Protein Function Prediction

Abstract

Mapping a protein sequence to its underlying biological function is a critical problem of increasing importance in biology. In this work, we propose ProtEx, a retrieval-augmented approach for protein function prediction that leverages exemplars from a database to improve accuracy and robustness and enable generalization to unseen classes. Our approach relies on a novel multi-sequence pretraining task, and a fine-tuning strategy that effectively conditions predictions on retrieved exemplars. Our method achieves state-of-the-art results across multiple datasets and settings for predicting Enzyme Commission (EC) numbers, Gene Ontology (GO) terms, and Pfam families. Our ablations and analysis highlight the impact of conditioning predictions on exemplar sequences, especially for classes and sequences less well represented in the training data.