ProtNote: a multimodal method for protein-function annotation.

Abstract

Understanding the protein sequence-function relationship is essential for advancing protein biology and engineering. However, <1% of known protein sequences have human-verified functions. While deep-learning methods have demonstrated promise for protein-function prediction, current models are limited to predicting only those functions on which they were trained. Here, we introduce ProtNote, a multimodal deep-learning model that leverages free-form text to enable both supervised and zero-shot protein-function prediction. ProtNote not only maintains near state-of-the-art performance for annotations in its training set but also generalizes to unseen and novel functions in zero-shot test settings. ProtNote demonstrates superior performance in the prediction of novel Gene Ontology annotations and Enzyme Commission numbers compared to baseline models by capturing nuanced sequence-function relationships that unlock a range of biological use cases inaccessible to prior models. We envision that ProtNote will enhance protein-function discovery by enabling scientists to use free text inputs without restriction to predefined labels-a necessary capability for navigating the dynamic landscape of protein biology. The code is available on GitHub: https://github.com/microsoft/protnote; model weights, datasets, and evaluation metrics are provided via Zenodo: https://zenodo.org/records/13897920.