A weighted bilinear neural collaborative filtering approach for drug repositioning.

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Abstract

Drug repositioning is an efficient and promising strategy for traditional drug discovery and development. Many research efforts are focused on utilizing deep-learning approaches based on a heterogeneous network for modeling complex drug-disease associations. Similar to traditional latent factor models, which directly factorize drug-disease associations, they assume the neighbors are independent of each other in the network and thus tend to be ineffective to capture localized information. In this study, we propose a novel neighborhood and neighborhood interaction-based neural collaborative filtering approach (called DRWBNCF) to infer novel potential drugs for diseases. Specifically, we first construct three networks, including the known drug-disease association network, the drug-drug similarity and disease-disease similarity networks (using the nearest neighbors). To take the advantage of localized information in the three networks, we then design an integration component by proposing a new weighted bilinear graph convolution operation to integrate the information of the known drug-disease association, the drug’s and disease’s neighborhood and neighborhood interactions into a unified representation. Lastly, we introduce a prediction component, which utilizes the multi-layer perceptron optimized by the α-balanced focal loss function and graph regularization to model the complex drug-disease associations. Benchmarking comparisons on three datasets verified the effectiveness of DRWBNCF for drug repositioning. Importantly, the unknown drug-disease associations predicted by DRWBNCF were validated against clinical trials and three authoritative databases and we listed several new DRWBNCF-predicted potential drugs for breast cancer (e.g. valrubicin and teniposide) and small cell lung cancer (e.g. valrubicin and cytarabine).© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected].