In this study, we introduce an interpretable graph-based deep learning prediction model, AttentionSiteDTI, which utilizes protein binding sites along with a self-attention mechanism to address the problem of drug–target interaction prediction. Our proposed model is inspired by sentence classification models in the field of Natural Language Processing, where the drug–target complex is treated as a sentence with relational meaning between its biochemical entities a.k.a. protein pockets and drug molecule. AttentionSiteDTI enables interpretability by identifying the protein binding sites that contribute the most toward the drug–target interaction. Results on three benchmark datasets show improved performance compared with the current state-of-the-art models. More significantly, unlike previous studies, our model shows superior performance, when tested on new proteins (i.e. high generalizability). Through multidisciplinary collaboration, we further experimentally evaluate the practical potential of our proposed approach. To achieve this, we first computationally predict the binding interactions between some candidate compounds and a target protein, then experimentally validate the binding interactions for these pairs in the laboratory. The high agreement between the computationally predicted and experimentally observed (measured) drug–target interactions illustrates the potential of our method as an effective pre-screening tool in drug repurposing applications.

At the time of this study, the SARS-CoV-2 virus that caused the COVID-19 pandemic has spread significantly across the world. Considering the uncertainty about policies, health risks, financial difficulties, etc. the online media, especially the Twitter platform, is experiencing a high volume of activity related to this pandemic. Among the hot topics, the polarized debates about unconfirmed medicines for the treatment and prevention of the disease have attracted significant attention from online media users. In this work, we present a stance data set, COVID-CQ, of user-generated content on Twitter in the context of COVID-19. We investigated more than 14 thousand tweets and manually annotated the tweet initiators’ opinions regarding the use of “chloroquine” and “hydroxychloroquine” for the treatment or prevention of COVID-19. To the best of our knowledge, COVID-CQ is the first data set of Twitter users’ stances in the context of the COVID-19 pandemic, and the largest Twitter data set on users’ stances towards a claim, in any domain. We have made this data set available to the research community via the Mendeley Data repository. We expect this data set to be useful for many research purposes, including stance detection, evolution and dynamics of opinions regarding this outbreak, and changes in opinions in response to the exogenous shocks such as policy decisions and events.

Drug-target interaction (DTI) prediction through in vitro methods is expensive and time-consuming. On the other hand, computational methods can save time and money while enhancing drug discovery efficiency. Most of the computational methods frame DTI prediction as a binary classification task. One important challenge is that the number of negative interactions in all DTI-related datasets is far greater than the number of positive interactions, leading to the class imbalance problem. As a result, a classifier is trained biased towards the majority class (negative class), whereas the minority class (interacting pairs) is of interest. This class imbalance problem is not widely taken into account in DTI prediction studies, and the few previous studies considering balancing in DTI do not focus on the imbalance issue itself. Additionally, they do not benefit from deep learning models and experimental validation. In this study, we propose a computational framework along with experimental validations to predict drug-target interaction using an ensemble of deep learning models to address the class imbalance problem in the DTI domain. The objective of this paper is to mitigate the bias in the prediction of DTI by focusing on the impact of balancing and maintaining other involved parameters at a constant value. Our analysis shows that the proposed model outperforms unbalanced models with the same architecture trained on the BindingDB both computationally and experimentally. These findings demonstrate the significance of balancing, which reduces the bias towards the negative class and leads to better performance. It is important to note that leaning on computational results without experimentally validating them and by relying solely on AUROC and AUPRC metrics is not credible, particularly when the testing set remains unbalanced.

While research into drug–target interaction (DTI) prediction is fairly mature, generalizability and interpretability are not always addressed in the existing works in this field. In this paper, we propose a deep learning (DL)-based framework, called BindingSite-AugmentedDTA, which improves drug–target affinity (DTA) predictions by reducing the search space of potential-binding sites of the protein, thus making the binding affinity prediction more efficient and accurate. Our BindingSite-AugmentedDTA is highly generalizable as it can be integrated with any DL-based regression model, while it significantly improves their prediction performance. Also, unlike many existing models, our model is highly interpretable due to its architecture and self-attention mechanism, which can provide a deeper understanding of its underlying prediction mechanism by mapping attention weights back to protein-binding sites. The computational results confirm that our framework can enhance the prediction performance of seven state-of-the-art DTA prediction algorithms in terms of four widely used evaluation metrics, including concordance index, mean squared error, modified squared correlation coefficient ($r^2_m$) and the area under the precision curve. We also contribute to three benchmark drug–traget interaction datasets by including additional information on 3D structure of all proteins contained in those datasets, which include the two most commonly used datasets, namely Kiba and Davis, as well as the data from IDG-DREAM drug-kinase binding prediction challenge. Furthermore, we experimentally validate the practical potential of our proposed framework through in-lab experiments. The relatively high agreement between computationally predicted and experimentally observed binding interactions supports the potential of our framework as the next-generation pipeline for prediction models in drug repurposing.

Sinus of Valsalva aneurysm is a rare congenital or acquired aortic root anomaly. The aneurysm has the potential to compress the adjacent structures or rupture to other cardiac chambers with fatal consequences. Patients might be asymptomatic or present with nonspecific cardiac symptoms. Once the diagnosis is made, prompt surgical repair is generally required. Here, we present a young woman with frequent syncope who was found to have a giant sinus of Valsalva aneurysm as the underlying etiology.