UniMatch: Universal Matching from Atom to Task for Few-Shot Drug Discovery

Abstract

Drug discovery is crucial for identifying candidate drugs for various diseases. However, its low success rate often results in a scarcity of annotations, posing a few-shot learning problem. Existing methods primarily focus on single-scale features, overlooking the hierarchical molecular structures that determine different molecular properties. To address these issues, we introduce Universal Matching Networks (UniMatch), a dual matching framework that integrates explicit hierarchical molecular matching with implicit task-level matching via meta- learning, bridging multi-level molecular representations and task-level generalization. Specifically, our approach explicitly captures structural features across multiple levels—atoms, substructures, and molecules—via hierarchical pooling and matching, facilitating precise molecular representation and comparison. Additionally, we employ a meta-learning strategy for implicit task-level matching, allowing the model to capture shared patterns across tasks and quickly adapt to new ones. This unified matching framework ensures effective molecular alignment while leveraging shared meta-knowledge for fast adaptation. Our experimental results demonstrate that UniMatch outperforms state-of-the-art methods on the MoleculeNet and FS-Mol benchmarks, achieving improvements of 2.87% in AUROC and 6.52% in ∆AUPRC. UniMatch also shows excellent generalization ability on the Meta-MolNet benchmark.