ABSTRACT
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.
Subject(s)
Algorithms , Drug Repositioning , Drug Development , Proteins/chemistry , Binding SitesABSTRACT
Modeling the information of social contagion processes has recently attracted a substantial amount of interest from researchers due to its wide applicability in network science, multi-agent-systems, information science, and marketing. Unlike in biological spreading, the existence of a reinforcement effect in social contagion necessitates considering the complexity of individuals in the systems. Although many studies acknowledged the heterogeneity of the individuals in their adoption of information, there are no studies that take into account the individuals' uncertainty during their adoption decision-making. This resulted in less than optimal modeling of social contagion dynamics in the existence of phase transition in the final adoption size versus transmission probability. We employed the Inverse Born Problem (IBP) to represent probabilistic entities as complex probability amplitudes in edge-based compartmental theory, and demonstrated that our novel approach performs better in the prediction of social contagion dynamics through extensive simulations on random regular networks.
