EMPDTA: An End-to-End Multimodal Representation Learning Framework with Pocket Online Detection for Drug-Target Affinity Prediction.

Accurately predicting drug-target interactions is a critical yet challenging task in drug discovery. Traditionally, pocket detection and drug-target affinity prediction have been treated as separate aspects of drug-target interaction, with few methods combining these tasks within a unified deep learning system to accelerate drug development. In this study, we propose EMPDTA, an end-to-end framework that integrates protein pocket prediction and drug-target affinity prediction to provide a comprehensive understanding of drug-target interactions. The EMPDTA framework consists of three main modules: pocket online detection, multimodal representation learning for affinity prediction, and multi-task joint training. The performance and potential of the proposed framework have been validated across diverse benchmark datasets, achieving robust results in both tasks. Furthermore, the visualization results of the predicted pockets demonstrate accurate pocket detection, confirming the effectiveness of our framework.

DRTerHGAT: A drug repurposing method based on the ternary heterogeneous graph attention network.

Drug repurposing is an effective method to reduce the time and cost of drug development. Computational drug repurposing can quickly screen out the most likely associations from large biological databases to achieve effective drug repurposing. However, building a comprehensive model that integrates drugs, proteins, and diseases for drug repurposing remains challenging. This study proposes a drug repurposing method based on the ternary heterogeneous graph attention network (DRTerHGAT). DRTerHGAT designs a novel protein feature extraction process consisting of a large-scale protein language model and a multi-task autoencoder, so that protein features can be extracted accurately and efficiently from amino acid sequences. The ternary heterogeneous graph of drug-protein-disease comprehensively considering the relationships among the three types of nodes, including three homogeneous and three heterogeneous relationships. Based on the graph and the extracted protein features, the deep features of the drugs and the diseases are extracted by graph convolutional networks (GCN) and heterogeneous graph node attention networks (HGNA). In the experiments, DRTerHGAT is proven superior to existing advanced methods and DRTerHGAT variants. DRTerHGAT's powerful ability for drug repurposing is also demonstrated in Alzheimer's disease.

MSFF-MA-DDI: Multi-Source Feature Fusion with Multiple Attention blocks for predicting Drug-Drug Interaction events.

The interaction of multiple drugs could lead to severe events, which cause medical injuries and expenses. Accurate prediction of drug-drug interaction (DDI) events can help clinicians make effective decisions and establish appropriate therapy programs. However, there exist two issues worthy of further consideration. (i) The global features of drug molecules should be paid attention to, rather than just their local characteristics. (ii) The fusion of multi-source features should also be studied to capture the comprehensive features of the drug. This study designs a Multi-Source Feature Fusion framework with Multiple Attention blocks named MSFF-MA-DDI that utilizes multimodal data for DDI event prediction. MSFF-MA-DDI can (i) encode global correlations between long-distance atoms in drug molecular sequences by a self-attention layer based on a position embedding block and (ii) fuse drug sequence features and heterogeneous features (chemical substructure, target, and enzyme) through a multi-head attention block to better represent the features of drugs. Experiments on real-world datasets show that MSFF-MA-DDI can achieve performance that is close to or even better than state-of-the-art models. Especially in cold start scenarios, the model can achieve the best performance. The effectiveness of the model is also supported by the case study on nervous system drugs. The source codes and data are available at https://github.com/BioCenter-SHU/MSFF-MA-DDI.

Small molecule drug and biotech drug interaction prediction based on multi-modal representation learning.

BACKGROUND: Drug-drug interactions (DDIs) occur when two or more drugs are taken simultaneously or successively. Early detection of adverse drug interactions can be essential in preventing medical errors and reducing healthcare costs. Many computational methods already predict interactions between small molecule drugs (SMDs). As the number of biotechnology drugs (BioDs) increases, so makes the threat of interactions between SMDs and BioDs. However, few computational methods are available to predict their interactions. RESULTS: Considering the structural specificity and relational complexity of SMDs and BioDs, a novel multi-modal representation learning method called Multi-SBI is proposed to predict their interactions. First, multi-modal features are used to adequately represent the heterogeneous structure and complex relationships of SMDs and BioDs. Second, an undersampling method based on Positive-unlabeled learning (PU-sampling) is introduced to obtain negative samples with high confidence from the unlabeled data set. Finally, both learned representations of SMD and BioD are fed into DNN classifiers to predict their interaction events. In addition, we also conduct a retrospective analysis. CONCLUSIONS: Our proposed multi-modal representation learning method can extract drug features more comprehensively in heterogeneous drugs. In addition, PU-sampling can effectively reduce the noise in the sampling procedure. Our proposed method significantly outperforms other state-of-the-art drug interaction prediction methods. In a retrospective analysis of DrugBank 5.1.0, 14 out of the 20 predictions with the highest confidence were validated in the latest version of DrugBank 5.1.8, demonstrating that Multi-SBI is a valuable tool for predicting new drug interactions through effectively extracting and learning heterogeneous drug features.

TP-DDI: A Two-Pathway Deep Neural Network for Drug-Drug Interaction Prediction.

Adverse drug-drug interactions (DDIs) can severely damage the body. Thus, it is essential to accurately predict DDIs. DDIs are complex processes in which many factors can cause interactions. Rather than merely considering one or two of the factors, we design a two-pathway drug-drug interaction framework named TP-DDI that uses multimodal data for DDI prediction. TP-DDI effectively explores the combined effect of a topological structure-based pathway and a biomedical object similarity-based pathway to obtain multimodal drug representations. For the topology-based pathway, we focus on drug chemistry structures through the self-attention mechanism, which can capture hidden critical relationships, especially between pairs of atoms at remote topological distances. For the similarity-based pathway, our model can emphasize useful biomedical objects according to the channel weights. Finally, the fusion of multimodal data provides a holistic view of DDIs by learning the complementary features. On a real-world dataset, experiments show that TP-DDI can achieve better performance than the state-of-the-art models. Moreover, we can find the most critical substructures with certain interpretability in the newly predicted DDIs.