The applicability of drug molecules in various clinical scenarios is significantly influenced by a diverse range of molecular properties. By leveraging self-supervised conditions such as atom attributes and interatomic bonds, existing advanced molecular foundation models can generate expressive representations of these molecules. However, such models often overlook the fixed association patterns within molecules that influence physiological or chemical properties. In this paper, we introduce a novel association pattern-aware message passing method, which can serve as an effective yet general plug-and-play plugin, thereby enhancing the atom representations generated by molecular foundation models without requiring additional pretraining. Additionally, molecular property-specific pattern libraries are constructed to collect the generated interpretable common patterns that bind to these properties. Extensive experiments conducted on 11 benchmark molecular property prediction tasks across 8 advanced molecular foundation models demonstrate significant superiority of the proposed method, with performance improvements of up to approximately 20%. Furthermore, a property-specific pattern library is tailored for blood-brain barrier penetration, which has undergone corresponding mechanistic validation.

Machine-learned interactions between drugs and human protein targets play a crucial role in efficient and accurate drug discovery. However, the drug-target mechanism of action (DTMoA) prediction is actually a multi-class classification problem, which follows a long-tailed class distribution. Existing methods simply address whether the drugs and targets can interact and rarely consider these deep mechanisms. In this paper, we introduce TED-DTMoA, a novel DTMoA prediction framework that incorporates the divide-and-conquer strategy with tri-comparison options. Specifically, to reduce the learning difficulty of tail classes, we propose an expertise-based divide-and-conquer decision approach that combines the results of multiple independent expertise models for sub-tasks decomposed from the original prediction task. In addition, to enhance the discrimination of similar mechanism classes, we devise a tri-comparison learning strategy that defines the sub-task as the classification of triple options, such as expanding the classification task for classes A and B to include an extra “Neither of them” option. Extensive experiments conducted on various DTMoA datasets quantitatively demonstrate the proposed method achieves an approximately 13% performance improvement compared with advanced baselines. Moreover, our method exhibits an obvious superiority on the tail classes. Further analysis of the evolvability and generalization reveals the significant potential to be deployed in real-world scenes.

Deep learning-based methods significantly advance the exploration of associations among triple-wise biological entities (e.g., drug-target protein-adverse reaction), thereby facilitating drug discovery and safeguarding human health. However, existing researches only focus on entity-centric information mapping and aggregation, neglecting the crucial role of potential association patterns among different entities. To address the above limitation, we propose a novel association pattern-aware fusion method for biological entity relationship prediction, which effectively integrates the related association pattern information into entity representation learning. Additionally, to enhance the missing information of the low-order message passing, we devise a bind-relation module that considers the strong bind of low-order entity associations. Extensive experiments conducted on three biological datasets quantitatively demonstrate that the proposed method achieves about 4%-23% hit@1 improvements compared with state-of-the-art baselines. Furthermore, the interpretability of association patterns is elucidated in detail, thus revealing the intrinsic biological mechanisms and promoting it to be deployed in real-world scenarios. Our data and code are available at https://github.com/hry98kki/PatternBERP.

The ability of molecular property prediction is of great significance to drug discovery. However, molecular property prediction is essentially a few-shot problem, making it a challenge in deep learning applications in this scenario. Although some deep learning models, such as meta-learning, have been used in few-shot molecular property prediction, they neglect the relationships among different properties. In this paper, we introduce a chemical property relation modeling technique for generating the property relation map, which can guide the few-shot molecular property prediction with positively related properties. Some molecules sharing common properties are firstly picked out. Then, multiple property-aware graph neural networks are trained for extracting molecular representations from those molecules. Next, the Spearman's correlation is adopted to calculate the property relations with the property-aware matrix, which is built by calculating the pairwise similarity of the above molecular representations for each pair of properties. In the few-shot molecular property prediction task, the meta-learning strategy is adopted to learn common prediction knowledge from the meta-training categories, which are provided by the property relations. Extensive experiments on two public few-shot molecular property datasets demonstrate that the positively related properties are beneficial for the target property prediction, while negatively related properties have negative effects. With the guidance of positively related properties, the proposed method outperforms various state-of-the-art methods.