Drug repositioning with adaptive graph convolutional networks.

MOTIVATION: Drug repositioning is an effective strategy to identify new indications for existing drugs, providing the quickest possible transition from bench to bedside. With the rapid development of deep learning, graph convolutional networks (GCNs) have been widely adopted for drug repositioning tasks. However, prior GCNs based methods exist limitations in deeply integrating node features and topological structures, which may hinder the capability of GCNs. RESULTS: In this study, we propose an adaptive GCNs approach, termed AdaDR, for drug repositioning by deeply integrating node features and topological structures. Distinct from conventional graph convolution networks, AdaDR models interactive information between them with adaptive graph convolution operation, which enhances the expression of model. Concretely, AdaDR simultaneously extracts embeddings from node features and topological structures and then uses the attention mechanism to learn adaptive importance weights of the embeddings. Experimental results show that AdaDR achieves better performance than multiple baselines for drug repositioning. Moreover, in the case study, exploratory analyses are offered for finding novel drug-disease associations. AVAILABILITY AND IMPLEMENTATION: The soure code of AdaDR is available at: https://github.com/xinliangSun/AdaDR.

BACPI: a bi-directional attention neural network for compound-protein interaction and binding affinity prediction.

MOTIVATION: The identification of compound-protein interactions (CPIs) is an essential step in the process of drug discovery. The experimental determination of CPIs is known for a large amount of funds and time it consumes. Computational model has therefore become a promising and efficient alternative for predicting novel interactions between compounds and proteins on a large scale. Most supervised machine learning prediction models are approached as a binary classification problem, which aim to predict whether there is an interaction between the compound and the protein or not. However, CPI is not a simple binary on-off relationship, but a continuous value reflects how tightly the compound binds to a particular target protein, also called binding affinity. RESULTS: In this study, we propose an end-to-end neural network model, called BACPI, to predict CPI and binding affinity. We employ graph attention network and convolutional neural network (CNN) to learn the representations of compounds and proteins and develop a bi-directional attention neural network model to integrate the representations. To evaluate the performance of BACPI, we use three CPI datasets and four binding affinity datasets in our experiments. The results show that, when predicting CPIs, BACPI significantly outperforms other available machine learning methods on both balanced and unbalanced datasets. This suggests that the end-to-end neural network model that predicts CPIs directly from low-level representations is more robust than traditional machine learning-based methods. And when predicting binding affinities, BACPI achieves higher performance on large datasets compared to other state-of-the-art deep learning methods. This comparison result suggests that the proposed method with bi-directional attention neural network can capture the important regions of compounds and proteins for binding affinity prediction. AVAILABILITY AND IMPLEMENTATION: Data and source codes are available at https://github.com/CSUBioGroup/BACPI.

NEDD: a network embedding based method for predicting drug-disease associations.

BACKGROUND: Drug discovery is known for the large amount of money and time it consumes and the high risk it takes. Drug repositioning has, therefore, become a popular approach to save time and cost by finding novel indications for approved drugs. In order to distinguish these novel indications accurately in a great many of latent associations between drugs and diseases, it is necessary to exploit abundant heterogeneous information about drugs and diseases. RESULTS: In this article, we propose a meta-path-based computational method called NEDD to predict novel associations between drugs and diseases using heterogeneous information. First, we construct a heterogeneous network as an undirected graph by integrating drug-drug similarity, disease-disease similarity, and known drug-disease associations. NEDD uses meta paths of different lengths to explicitly capture the indirect relationships, or high order proximity, within drugs and diseases, by which the low dimensional representation vectors of drugs and diseases are obtained. NEDD then uses a random forest classifier to predict novel associations between drugs and diseases. CONCLUSIONS: The experiments on a gold standard dataset which contains 1933 validated drug-disease associations show that NEDD produces superior prediction results compared with the state-of-the-art approaches.

StackCPA: A stacking model for compound-protein binding affinity prediction based on pocket multi-scale features.

Accurately predicting compound-protein binding affinity is a crucial task in drug discovery. Computational models offer the advantages of short time, low cost and safety compared to traditional drug development. Pocket is the key binding region of the protein, which provides invaluable information for drug repositioning and drug design. In this study, we propose an ensemble learning model, called StackCPA, to predict the compound-protein binding affinity. The model integrates multi-scale features of protein pocket and compound through a transfer learning strategy. The protein pocket is described in a fine-grained way by atomic level, residue level and subdomain level. The proposed model StackCPA is evaluated on three binding affinity benchmark datasets. The experiment results show that StackCPA achieves the best performance on all the three datasets in comparison with other state-of-the-art deep learning models. The ablation study shows that the protein pocket can provide sufficient information for affinity prediction and its multi-scale features enable the model to further improve the prediction performance. In addition, the case study for epidermal growth factor receptor erbB1 (EGFR) indicates that StackCPA could serve as an effective tool for drug repurposing. Source codes and data of StackCPA are available at https://github.com/CSUBioGroup/StackCPA.

A Medical Assistive Robot for Telehealth Care During the COVID-19 Pandemic: Development and Usability Study in an Isolation Ward.

BACKGROUND: The COVID-19 pandemic is affecting the mental and emotional well-being of patients, family members, and health care workers. Patients in the isolation ward may have psychological problems due to long-term hospitalization, the development of the epidemic, and the inability to see their families. A medical assistive robot (MAR), acting as an intermediary of communication, can be deployed to address these mental pressures. OBJECTIVE: CareDo, a MAR with telepresence and teleoperation functions, was developed in this work for remote health care. The aim of this study was to investigate its practical performance in the isolation ward during the pandemic. METHODS: Two systems were integrated into the CareDo robot. For the telepresence system, a web real-time communications solution is used for the multiuser chat system and a convolutional neural network is used for expression recognition. For the teleoperation system, an incremental motion mapping method is used for operating the robot remotely. A clinical trial of this system was conducted at First Affiliated Hospital, Zhejiang University. RESULTS: During the clinical trials, tasks such as video chatting, emotion detection, and medical supplies delivery were performed via the CareDo robot. Seven voice commands were set for performing system wakeup, video chatting, and system exiting. Durations from 1 to 3 seconds of common commands were set to improve voice command detection. The facial expression was recorded 152 times for a patient in 1 day for the psychological intervention. The recognition accuracy reached 95% and 92.8% for happy and neutral expressions, respectively. CONCLUSIONS: Patients and health care workers can use this MAR in the isolation ward for telehealth care during the COVID-19 pandemic. This can be a useful approach to break the chains of virus transmission and can also be an effective way to conduct remote psychological intervention.