DTI-MvSCA: An Anti-Over-Smoothing Multi-View Framework With Negative Sample Selection for Predicting Drug-Target Interactions

Predicting potential drug-target interactions (DTIs) facilitates to accelerate drug discovery and reduce development cost. Current deep learning-based methods exhibit high-performance predictions, but three challenges remain: first, the absence of negative DTIs severely limits the model performance. Moreover, existing graph neural networks are beset with the scalability due to the model complexity and graph size. More importantly, most methods focus on learning the topological features while ignoring node features during DTI representation learning. To solve the limitations, here, we develop a multi-view neural network framework called DTI-MvSCA for DTI identification. This framework begins with constructing a drug-protein pair (DPP) network with matrix operation-based negative DTI selection, and then learns the DPP representations through a <underline xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><b>M</b></u>ulti-<bold xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><u>v</u></b>iew neural network, finally classifies each DPP based on multilayer perceptron. Particularly, the multi-view neural network integrates graph topological feature learning based on the self-attention mechanism and <bold xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><u>S</u></b>HADOW graph attention network, node feature learning based on 1D <underline xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><b>C</b></u>onvolutional neural network, and the <bold xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><u>A</u></b>ttention mechanism. An in-depth experiment on DrugBank V3.0 and V5.0 showed that DTI-MvSCA obtained precise and robust predictions against five state-of-the-art baseline methods. Furthermore, visualizing the feature distributions of the selected negative DTIs exhibits a more distinguishable and clearer boundary. In summary, DTI-MvSCA provides a useful deep learning tool to investigate potential DTIs.