An Ensemble Matrix Completion Model for Predicting Potential Drugs Against SARS-CoV-2

Abstract

Because of the catastrophic outbreak of global coronavirus disease 2019 (COVID-19) and its strong infectivity and possible persistence, computational repurposing of existing approved drugs will be a promising strategy that facilitates rapid clinical treatment decisions and provides reasonable justification for subsequent clinical trials and regulatory reviews. Since the effects of a small number of conditionally marketed vaccines need further clinical observation, there is still an urgent need to quickly and effectively repurpose potentially available drugs before the next disease peak. In this work, we have manually collected a set of experimentally confirmed virus-drug associations through the publicly published database and literature, consisting of 175 drugs and 95 viruses, as well as 933 virus-drug associations. Then, because the samples are extremely sparse and unbalanced, negative samples cannot be easily obtained. We have developed an ensemble model, EMC-Voting, based on matrix completion and weighted soft voting, a semi-supervised machine learning model for computational drug repurposing. Finally, we have evaluated the prediction performance of EMC-Voting by fivefold crossing-validation and compared it with other baseline classifiers and prediction models. The case study for the virus SARS-COV-2 included in the dataset demonstrates that our model achieves the outperforming AUPR value of 0.934 in virus-drug association's prediction.

Keywords: SARS-CoV-2; computational drug repurposing; matrix completion; virus-drug association prediction; weighted voting ensemble model.

FIGURE 1

Flowchart of our work.

FIGURE 2

The ROC curve of EMC-voting by one time fivefold cross-validation.

FIGURE 3

Comparison of performance of different prediction models by Accuracy and F1 scores.

FIGURE 4

The results by 20 times fivefold CV. (A) ROC curve. (B) Precision-Recall curve.