Subgraph Information Bottleneck with Causal Dependency for Stable Molecular Relational Learning

Abstract

Molecular Relational Learning (MRL) is widely applied in molecular sciences. Recent studies attempt to retain molecular core information (e.g., substructures) by Graph Information Bottleneck but primarily focus on information compression without considering the causal dependencies of chemical reactions among substructures. This oversight neglects the core factors that determine molecular relationships, making maintaining stable MRL in distribution-shifted data challenging. To bridge this gap, we propose the Causal Subgraph Information Bottleneck (CausalGIB) for stable MRL. CausalGIB leverages causal dependency to guide substructure representation and integrates subgraph information bottleneck to optimize the core substructure representation, generating stable representations. Specifically, we distinguish causal and confounding substructures by noise injection and substructure interaction based on causal analysis. Furthermore, by minimizing the discrepancy between causal and confounding information within subgraph information bottleneck, CausalGIB captures core substructures composed of causal substructures and aggregates them into molecular representations to improve their stability. Experimental results on nine datasets demonstrate that CausalGIB outperforms state-of-the-art models in two tasks and significantly enhances model’s stability in distribution-shifted data.