DualNetGO: a dual network model for protein function prediction via effective feature selection

Protein-protein interaction (PPI) networks are crucial for automatically annotating protein functions. As multiple PPI networks exist for the same set of proteins that capture properties from different aspects, it is a challenging task to effectively utilize these heterogeneous networks. Recently, several deep learning models have combined PPI networks from all evidence, or concatenated all graph embeddings for protein function prediction. However, the lack of a judicious selection procedure prevents the effective harness of information from different PPI networks, as these networks vary in densities, structures, and noise levels. Consequently, combining protein features indiscriminately could increase the noise level, leading to decreased model performance.

We develop DualNetGO, a dual-network model comprised of a Classifier and a Selector, to predict protein functions by effectively selecting features from different sources including graph embeddings of PPI networks, protein domain, and subcellular location information. Evaluation of DualNetGO on human and mouse datasets in comparison with other network-based models shows at least 4.5%, 6.2%, and 14.2% improvement on Fmax in BP, MF, and CC gene ontology categories, respectively, for human, and 3.3%, 10.6%, and 7.7% improvement on Fmax for mouse. We demonstrate the generalization capability of our model by training and testing on the CAFA3 data, and show its versatility by incorporating Esm2 embeddings. We further show that our model is insensitive to the choice of graph embedding method and is time- and memory-saving. These results demonstrate that combining a subset of features including PPI networks and protein attributes selected by our model is more effective in utilizing PPI network information than only using one kind of or concatenating graph embeddings from all kinds of PPI networks.

The source code of DualNetGO and some of the experiment data are available at: https://github.com/georgedashen/DualNetGO.