Dataset Information

DDI-PULearn: a positive-unlabeled learning method for large-scale prediction of drug-drug interactions.

ABSTRACT:

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.

SUBMITTER: Zheng Y

PROVIDER: S-EPMC6929327 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Publications

DDI-PULearn: a positive-unlabeled learning method for large-scale prediction of drug-drug interactions.

Zheng Yi Y Peng Hui H Zhang Xiaocai X Zhao Zhixun Z Gao Xiaoying X Li Jinyan J

BMC bioinformatics 20191224 Suppl 19

<h4>Background</h4>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.<h4>Results</h4>To address this problem, we propose a novel positive-unlabeled learning method named DDI-PULearn for large-scale drug-drug-interaction p ...[more]

PMID: 31870276

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Project description:MotivationProtein phosphorylation is a post-translational modification that underlines various aspects of cellular signaling. A key step to reconstructing signaling networks involves identification of the set of all kinases and their substrates. Experimental characterization of kinase substrates is both expensive and time-consuming. To expedite the discovery of novel substrates, computational approaches based on kinase recognition sequence (motifs) from known substrates, protein structure, interaction and co-localization have been proposed. However, rarely do these methods take into account the dynamic responses of signaling cascades measured from in vivo cellular systems. Given that recent advances in mass spectrometry-based technologies make it possible to quantify phosphorylation on a proteome-wide scale, computational approaches that can integrate static features with dynamic phosphoproteome data would greatly facilitate the prediction of biologically relevant kinase-specific substrates.ResultsHere, we propose a positive-unlabeled ensemble learning approach that integrates dynamic phosphoproteomics data with static kinase recognition motifs to predict novel substrates for kinases of interest. We extended a positive-unlabeled learning technique for an ensemble model, which significantly improves prediction sensitivity on novel substrates of kinases while retaining high specificity. We evaluated the performance of the proposed model using simulation studies and subsequently applied it to predict novel substrates of key kinases relevant to insulin signaling. Our analyses show that static sequence motifs and dynamic phosphoproteomics data are complementary and that the proposed integrated model performs better than methods relying only on static information for accurate prediction of kinase-specific substrates.Availability and implementationExecutable GUI tool, source code and documentation are freely available at https://github.com/PengyiYang/KSP-PUEL.Contactpengyi.yang@nih.gov or jothi@mail.nih.govSupplementary informationSupplementary data are available at Bioinformatics online.

Dataset Information

DDI-PULearn: a positive-unlabeled learning method for large-scale prediction of drug-drug interactions.

Background

Results

Conclusions

Publications

DDI-PULearn: a positive-unlabeled learning method for large-scale prediction of drug-drug interactions.

Similar Datasets

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