Optimizing OOD Detection in Molecular Graphs: A Novel Approach with Diffusion Models

Despite the recent progress of molecular representation learning, its effectiveness is assumed on the close-world assumptions that training and testing graphs are from identical distribution. The open-world test dataset is often mixed with out-of-distribution (OOD) samples, where the deployed models will struggle to make accurate predictions. The misleading estimations of molecules' properties in drug screening or design can result in the tremendous waste of wet-lab resources and delay the discovery of novel therapies. Traditional detection methods need to trade off OOD detection and in-distribution (ID) classification performance since they share the same representation learning model. In this work, we propose to detect OOD molecules by adopting an auxiliary diffusion model-based framework, which compares similarities between input molecules and reconstructed graphs. Due to the generative bias towards reconstructing ID training samples, the similarity scores of OOD molecules will be much lower to facilitate detection. Although it is conceptually simple, extending this vanilla framework to practical detection applications is still limited by two significant challenges. First, the popular similarity metrics based on Euclidian distance fail to consider the complex graph structure. Second, the generative model involving iterative denoising steps is notoriously time-consuming especially when it runs on the enormous pool of drugs. To address these challenges, our research pioneers an approach of Prototypical Graph Reconstruction for Molecular OOd Detection, dubbed as PGR-MOOD. Specifically, PGR-MOOD hinges on three innovations: i) An effective metric to comprehensively quantify the matching degree of input and reconstructed molecules according to their discrete edges and continuous node features; ii) A creative graph generator to construct a list of prototypical graphs that are in line with ID distribution but away from OOD one; iii) An efficient and scalable OOD detector to compare the similarity between test samples and pre-constructed prototypical graphs and omit the generative process on every new molecule. Extensive experiments on ten benchmark datasets and six baselines are conducted to demonstrate our superiority: PGR-MOOD achieves more than 8% of average improvement in terms of detection AUC and AUPR accompanied by the reduced cost of testing time and memory consumption. The anonymous code is in: https://github.com/se7esx/PGR-MOOD.