GraphIsoFun: a graph neural network based approach for splice isoform function prediction

Alternative splicing has a significant impact in the process of gene regulation and it greatly raises the complexity of protein species and functions. At present, the gene function has been extensively studied, and there are multiple public databases of gene function annotations. Due to the high cost and the large number of isoforms, it is currently impossible to conduct extensive experimental analysis on isoform functions. Functions at the level of splicing isoforms remain largely unknown. Computational prediction provides an alternative to functional annotation of splice isoforms. Here we present GraphIsoFun, a novel computational approach to predict isoform function by integrating both gene and isoform-level expression information with graph neural network. It first constructs a heterogeneous co-expression network with both genes and isoforms being nodes. This network integrates the rich association between isoforms and genes, and provides a bridge for connecting isoform and gene functions. Then GraphIsoFun uses the graph neural network to mine the information of the co-expression network and obtains the final prediction score of isoforms for each function. The experiments on multiple datasets show that GraphIsoFun surpasses existing methods based on different evaluation indicators.