Large-scale predicting protein functions through heterogeneous feature fusion

As the volume of protein sequence and structure data grows rapidly, the functions of the overwhelming majority of proteins cannot be experimentally determined. Automated annotation of protein function at a large scale is becoming increasingly important. Existing computational prediction methods are typically based on expanding the relatively small number of experimentally determined functions to large collections of proteins with various clues, including sequence homology, protein-protein interaction, gene co-expression, etc. Although there has been some progress in protein function prediction in recent years, the development of accurate and reliable solutions still has a long way to go. Here we exploit AlphaFold predicted three-dimensional structural information, together with other non-structural clues, to develop a large-scale approach termed PredGO to annotate Gene Ontology (GO) functions for proteins. We use a pre-trained language model, geometric vector perceptrons and attention mechanisms to extract heterogeneous features of proteins and fuse these features for function prediction. The computational results demonstrate that the proposed method outperforms other state-of-the-art approaches for predicting GO functions of proteins in terms of both coverage and accuracy. The improvement of coverage is because the number of structures predicted by AlphaFold is greatly increased, and on the other hand, PredGO can extensively use non-structural information for functional prediction. Moreover, we show that over 205 000 ($\sim $100%) entries in UniProt for human are annotated by PredGO, over 186 000 ($\sim $90%) of which are based on predicted structure. The webserver and database are available at http://predgo.denglab.org/.