EssSubgraph improves performance and generalizability of mammalian essential gene prediction with large networks.

Predicting essential genes is important for understanding the minimal genetic requirements of organisms, identifying disease-associated genes, and discovering potential drug targets. Wet-lab experiments for identifying essential genes are time-consuming and labor-intensive. Although various machine learning methods have been developed for essential gene prediction, both systematic testing with large collections of gene knockout data and rigorous benchmarking for efficient methods are very limited to date. Furthermore, current graph-based approaches require learning the entire gene interaction networks, leading to high computational costs, especially for large-scale networks. To address these issues, we propose EssSubgraph, an inductive representation learning method that integrates graph-structured network data with omics features for training graph neural networks. We used comprehensive lists of human essential genes distilled from the latest collection of knockout datasets for benchmarking. When applied to essential gene prediction with multiple types of biological networks, EssSubgraph achieved superior performance compared to existing graph-based and other models. The performance is more stable than other methods with respect to network structure and gene feature perturbations. Because of its inductive nature, EssSubgraph also enables predicting gene functions using dynamical networks with unseen nodes and it is scalable with respect to network sizes. Finally, EssSubgraph has better performance in cross-species essential gene prediction compared to other methods. Our results show that EssSubgraph effectively combines networks and omics data for accurate essential gene identification while maintaining computational efficiency. The source code and datasets used in this study are freely available at https://github.com/wenmm/EssSubgraph .