Autoencoder-based drug-virus association prediction with reliable negative sample selection: A case study with...

Emergence of viruses cause unprecedented challenges and thus leading to wide-ranging consequences today. The world has faced massive disruptions like COVID-19 and continues to suffer in terms of public health and world economy. Fighting with this emergence of viruses and its reemergence plays a critical role in the health care industry. Identification of novel virus-drug associations is a vital step in drug discovery. Prediction and prioritization of novel virus-drug associations through computational approaches is an alternative and best choice considering the cost and risk of biological experiments. This study proposes a method, KR-AEVDA that relies on k-nearest neighbor based reliable negative sample selection and autoencoder based feature extraction to explore promising virus-drug associations for further experimental validation. The method analyzes complex relationships among drugs and viruses by investigating similarity and association data between drugs and viruses. It generates feature vectors from the similarity data, and reliable negative samples are extracted through an effective distance-based algorithm from the unlabeled samples in the dataset. Then high level features are extracted via an autoencoder and is fed to an ensemble classifier for inferring novel associations. Experimental results on three different datasets showed that KR-AEVDA reliably attained better performance than other state-of-the-art methods. Molecular docking is carried out between the top-predicted drugs and the crystal structure of the SARS-CoV-2's main protease to further validate the predictions. Case studies for SARS-CoV-2 illustrate the effectiveness of KR-AEVDA in identifying potential virus-drug associations.