Abstract:Effective gene network representation learning is of great importance in bioinformatics to predict/understand the relation of gene profiles and disease phenotypes. Though graph neural networks (GNNs) have been the dominant architecture for analyzing various graph-structured data like social networks, their predicting on gene networks often exhibits subpar performance. In this paper, we formally investigate the gene network representation learning problem and characterize a notion of \textit{universal graph normalization}, where graph normalization can be applied in an universal manner to maximize the expressive power of GNNs while maintaining the stability. We propose a novel UNGNN (Universal Normalized GNN) framework, which leverages universal graph normalization in both the message passing phase and readout layer to enhance the performance of a base GNN. UNGNN has a plug-and-play property and can be combined with any GNN backbone in practice. A comprehensive set of experiments on gene-network-based bioinformatical tasks demonstrates that our UNGNN model significantly outperforms popular GNN benchmarks and provides an overall performance improvement of 16 $\%$ on average compared to previous state-of-the-art (SOTA) baselines. Furthermore, we also evaluate our theoretical findings on other graph datasets where the universal graph normalization is solvable, and we observe that UNGNN consistently achieves the superior performance.