Multi-omics Sampling-based Graph Transformer for Synthetic Lethality Prediction

Abstract

Synthetic lethality (SL) prediction is used to identify if the co-mutation of two genes results in cell death. The prevalent strategy is to abstract SL prediction as an edge classification task on gene nodes within SL data and achieve it through graph neural networks (GNNs). However, GNNs suffer from limitations in their message passing mechanisms, including over-smoothing and over-squashing issues. Moreover, harnessing the information of non-SL gene relationships within large-scale multi-omics data to facilitate SL prediction poses a non-trivial challenge. To tackle these issues, we propose a new multi-omics sampling-based graph transformer for SL prediction (MSGT-SL). Concretely, we introduce a shallow multi-view GNN to acquire local structural patterns from both SL and multi-omics data. Further, we input gene features that encode multi-view information into the standard self-attention to capture long-range dependencies. Notably, starting with batch genes from SL data, we adopt parallel random walk sampling across multiple omics gene graphs encompassing them. Such sampling effectively and modestly incorporates genes from omics in a structure-aware manner before using self-attention. We showcase the effectiveness of MSGT-SL on real-world SL tasks, demonstrating the empirical benefits gained from the graph transformer and multi-omics data.