Identifying suitable reaction conditions is critical for chemical synthesis, as they directly affect yield, selectivity, and transformation feasibility. While recent methods have shown promising results, most approaches either encode reactants and products independently or rely on rule-based reaction graphs, both of which constrain the ability of the model to capture condition-relevant structural transformations. In this work, we propose TRACE, a transformation-aware graph refinement framework for reaction condition prediction. TRACE constructs atom-level joint graphs that integrate both reactant and product structures to represent condition-relevant transformations. A structure-aware encoder enriches atom features with local chemical context, followed by a dynamic interaction refinement module that adaptively infers task-specific edges. To further guide the model toward condition-relevant patterns, a mechanism regularized graph encoder incorporates reaction center information, enabling more accurate modeling of transformation mechanisms. Experiments on benchmark datasets show that TRACE achieves state-of-the-art performance across multiple condition types. The integration of transformation-aware refinement leads to improvements in prediction accuracy and generalization, while maintaining robust performance in challenging and realistic synthesis planning scenarios.

Inductive Knowledge Graph Completion (KGC) aims to infer missing facts between newly emerged entities within knowledge graphs (KGs), posing a significant challenge. While recent studies have shown promising results in inferring such entities through knowledge subgraph reasoning, they suffer from (i) the semantic inconsistencies of similar relations, and (ii) noisy interactions inherent in KGs due to the presence of unconvincing knowledge for emerging entities. To address these challenges, we propose a Semantic Structure-aware Denoising Network (S2DN) for inductive KGC. Our goal is to learn adaptable general semantics and reliable structures to distill consistent semantic knowledge while preserving reliable interactions within KGs. Specifically, we introduce a semantic smoothing module over the enclosing subgraphs to retain the universal semantic knowledge of relations. We incorporate a structure refining module to filter out unreliable interactions and offer additional knowledge, retaining robust structure surrounding target links. Extensive experiments conducted on three benchmark KGs demonstrate that S2DN surpasses the performance of state-of-the-art models. These results demonstrate the effectiveness of S2DN in preserving semantic consistency and enhancing the robustness of filtering out unreliable interactions in contaminated KGs.

Identifying drug-drug interactions (DDIs) is critical for ensuring drug safety and advancing drug development, a topic that has garnered significant research interest. While existing methods have made considerable progress, approaches relying solely on known DDIs face a key challenge when applied to drugs with limited data: insufficient exploration of the space of unlabeled pairwise drugs. To address these issues, we innovatively introduce S$^2$VM, a Self-supervised Visual pretraining framework for pair-wise Molecules, to fully fuse structural representations and explore the space of drug pairs for DDI prediction. S$^2$VM incorporates the explicit structure and correlations of visual molecules, such as the positional relationships and connectivity between functional substructures. Specifically, we blend the visual fragments of drug pairs into a unified input for joint encoding and then recover molecule-specific visual information for each drug individually. This approach integrates fine-grained structural representations from unlabeled drug pair data. By using visual fragments as anchors, S$^2$VM effectively captures the spatial information of local molecular components within visual molecules, resulting in more comprehensive embeddings of drug pairs. Experimental results show that S$^2$VM achieves state-of-the-art performance on widely used benchmarks, with Macro-F1 score improvements of 4.21% and 3.31%, respectively. Further extensive results and theoretical analysis demonstrate the effectiveness of S$^2$VM for both few-shot and novel drugs.

Molecular interaction prediction plays a crucial role in forecasting unknown interactions between molecules, such as drug-target interaction (DTI) and drug-drug interaction (DDI), which are essential in the field of drug discovery and therapeutics. Although previous prediction methods have yielded promising results by leveraging the rich semantics and topological structure of biomedical knowledge graphs (KGs), they have primarily focused on enhancing predictive performance without addressing the presence of inevitable noise and inconsistent semantics. This limitation has hindered the advancement of KG-based prediction methods. To address this limitation, we propose BioKDN (BiomedicalKnowledge GraphDenoisingNetwork) for robust molecular interaction prediction. BioKDN refines the reliable structure of local subgraphs by denoising noisy links in a learnable manner, providing a general module for extracting task-relevant interactions. To enhance the reliability of the refined structure, BioKDN maintains consistent and robust semantics by smoothing relations around the target interaction. By maximizing the mutual information between reliable structure and smoothed relations, BioKDN emphasizes informative semantics to enable precise predictions. Experimental results on real-world datasets show that BioKDN surpasses state-of-the-art models in DTI and DDI prediction tasks, confirming the effectiveness and robustness of BioKDN in denoising unreliable interactions within contaminated KGs.

MOTIVATION: Adverse drug-drug interactions (DDIs) are crucial for drug research and mainly cause morbidity and mortality. Thus, the identification of potential DDIs is essential for doctors, patients and the society. Existing traditional machine learning models rely heavily on handcraft features and lack generalization. Recently, the deep learning approaches that can automatically learn drug features from the molecular graph or drug-related network have improved the ability of computational models to predict unknown DDIs. However, previous works utilized large labeled data and merely considered the structure or sequence information of drugs without considering the relations or topological information between drug and other biomedical objects (e.g. gene, disease and pathway), or considered knowledge graph (KG) without considering the information from the drug molecular structure. RESULTS: Accordingly, to effectively explore the joint effect of drug molecular structure and semantic information of drugs in knowledge graph for DDI prediction, we propose a multi-scale feature fusion deep learning model named MUFFIN. MUFFIN can jointly learn the drug representation based on both the drug-self structure information and the KG with rich bio-medical information. In MUFFIN, we designed a bi-level cross strategy that includes cross- and scalar-level components to fuse multi-modal features well. MUFFIN can alleviate the restriction of limited labeled data on deep learning models by crossing the features learned from large-scale KG and drug molecular graph. We evaluated our approach on three datasets and three different tasks including binary-class, multi-class and multi-label DDI prediction tasks. The results showed that MUFFIN outperformed other state-of-the-art baselines. AVAILABILITY AND IMPLEMENTATION: The source code and data are available at https://github.com/xzenglab/MUFFIN.