A Robust Drug-Target Interaction Prediction Framework with Capsule Network and Transfer Learning.

Drug-target interactions (DTIs) are considered a crucial component of drug design and drug discovery. To date, many computational methods were developed for drug-target interactions, but they are insufficiently informative for accurately predicting DTIs due to the lack of experimentally verified negative datasets, inaccurate molecular feature representation, and ineffective DTI classifiers. Therefore, we address the limitations of randomly selecting negative DTI data from unknown drug-target pairs by establishing two experimentally validated datasets and propose a capsule network-based framework called CapBM-DTI to capture hierarchical relationships of drugs and targets, which adopts pre-trained bidirectional encoder representations from transformers (BERT) for contextual sequence feature extraction from target proteins through transfer learning and the message-passing neural network (MPNN) for the 2-D graph feature extraction of compounds to accurately and robustly identify drug-target interactions. We compared the performance of CapBM-DTI with state-of-the-art methods using four experimentally validated DTI datasets of different sizes, including human (Homo sapiens) and worm (Caenorhabditis elegans) species datasets, as well as three subsets (new compounds, new proteins, and new pairs). Our results demonstrate that the proposed model achieved robust performance and powerful generalization ability in all experiments. The case study on treating COVID-19 demonstrates the applicability of the model in virtual screening.

ABT-MPNN: an atom-bond transformer-based message-passing neural network for molecular property prediction.

Graph convolutional neural networks (GCNs) have been repeatedly shown to have robust capacities for modeling graph data such as small molecules. Message-passing neural networks (MPNNs), a group of GCN variants that can learn and aggregate local information of molecules through iterative message-passing iterations, have exhibited advancements in molecular modeling and property prediction. Moreover, given the merits of Transformers in multiple artificial intelligence domains, it is desirable to combine the self-attention mechanism with MPNNs for better molecular representation. We propose an atom-bond transformer-based message-passing neural network (ABT-MPNN), to improve the molecular representation embedding process for molecular property predictions. By designing corresponding attention mechanisms in the message-passing and readout phases of the MPNN, our method provides a novel architecture that integrates molecular representations at the bond, atom and molecule levels in an end-to-end way. The experimental results across nine datasets show that the proposed ABT-MPNN outperforms or is comparable to the state-of-the-art baseline models in quantitative structure-property relationship tasks. We provide case examples of Mycobacterium tuberculosis growth inhibitors and demonstrate that our model's visualization modality of attention at the atomic level could be an insightful way to investigate molecular atoms or functional groups associated with desired biological properties. The new model provides an innovative way to investigate the effect of self-attention on chemical substructures and functional groups in molecular representation learning, which increases the interpretability of the traditional MPNN and can serve as a valuable way to investigate the mechanism of action of drugs.

Dynamic graph neural network with adaptive edge attributes for air quality prediction: A case study in China.

Air quality prediction is a typical Spatiotemporal modeling problem, which always uses different components to handle spatial and temporal dependencies in complex systems separately. Previous models based on time series analysis and recurrent neural network (RNN) methods have only modeled time series while ignoring spatial information. Previous graph convolution neural networks (GCNs) based methods usually require providing spatial correlation graph structure of observation sites in advance. The correlations among these sites and their strengths are usually calculated using prior information. However, due to the limitations of human cognition, limited prior information cannot reflect the real station-related structure or bring more effective information for accurate prediction. To this end, we propose a novel Dynamic Graph Neural Network with Adaptive Edge Attributes (DGN-AEA) on the message passing network, which generates the adaptive bidirected dynamic graph by learning the edge attributes as model parameters. Unlike prior information to establish edges, our method can obtain adaptive edge information through end-to-end training without any prior information. Thus reducing the complexity of the problem. Besides, the hidden structural information between the stations can be obtained as model by-products, which can help make some subsequent decision-making analyses. Experimental results show that our model received state-of-the-art performance than other baselines.