Background: Drug-drug interactions (DDIs) are a major concern in patients' medication. It's unfeasible to identify all potential DDIs using experimental methods which are time-consuming and expensive. Computational methods provide an effective strategy, however, facing challenges due to the lack of experimentally verified negative samples. Results: To address this problem, we propose a novel positive-unlabeled learning method named DDI-PULearn for large-scale drug-drug-interaction predictions. DDI-PULearn first generates seeds of reliable negatives via OCSVM (one-class support vector machine) under a high-recall constraint and via the cosine-similarity based KNN (k-nearest neighbors) as well. Then trained with all the labeled positives (i.e., the validated DDIs) and the generated seed negatives, DDI-PULearn employs an iterative SVM to identify a set of entire reliable negatives from the unlabeled samples (i.e., the unobserved DDIs). Following that, DDI-PULearn represents all the labeled positives and the identified negatives as vectors of abundant drug properties by a similarity-based method. Finally, DDI-PULearn transforms these vectors into a lower-dimensional space via PCA (principal component analysis) and utilizes the compressed vectors as input for binary classifications. The performance of DDI-PULearn is evaluated on simulative prediction for 149,878 possible interactions between 548 drugs, comparing with two baseline methods and five state-of-the-art methods. Related experiment results show that the proposed method for the representation of DDIs characterizes them accurately. DDI-PULearn achieves superior performance owing to the identified reliable negatives, outperforming all other methods significantly. In addition, the predicted novel DDIs suggest that DDI-PULearn is capable to identify novel DDIs. Conclusions: The results demonstrate that positive-unlabeled learning paves a new way to tackle the problem caused by the lack of experimentally verified negatives in the computational prediction of DDIs.
CITATION STYLE
Zheng, Y., Peng, H., Zhang, X., Zhao, Z., Gao, X., & Li, J. (2019). DDI-PULearn: A positive-unlabeled learning method for large-scale prediction of drug-drug interactions. BMC Bioinformatics, 20. https://doi.org/10.1186/s12859-019-3214-6
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