Isoform Function Prediction Based on Heterogeneous Graph Attention Networks

Isoforms refer to different mRNA molecules transcribed from the same gene, which can be translated into proteins with varying structures and functions. Predicting the functions of isoforms is an essential topic in bioinformatics as it can provide valuable insights into the intricate mechanisms of gene regulation and biological processes. Conventionally, gene function labels are standardized in Gene Ontology (GO) terms. However, traditional methods for predicting isoform function are largely limited by the absence of isoform-specific labels, sparse annotations, and the vast number of GO terms. To address these issues, we propose HANIso, a deep learning-based method for isoform function prediction. HANIso leverages a pretrained protein language model to extract features from protein sequences. It also integrates heterogeneous information, such as isoform sequence features, GO annotations, and isoform interaction data, using a Heterogeneous Graph Attention Network (HAN). This allows the model to learn the importance of different sources of information and their semantic relationships through the attention mechanism. Our method can predict function labels at both the gene level and isoform level. We conduct experiments on two species datasets, and the results demonstrate that our method outperforms existing methods on both AUROC and AUPRC. HANIso has the potential to overcome the limitations of traditional methods and provide a more accurate and comprehensive understanding of isoform function.