Dataset Information

Comparison of Target Features for Predicting Drug-Target Interactions by Deep Neural Network Based on Large-Scale Drug-Induced Transcriptome Data.

ABSTRACT: Uncovering drug-target interactions (DTIs) is pivotal to understand drug mode-of-action (MoA), avoid adverse drug reaction (ADR), and seek opportunities for drug repositioning (DR). For decades, in silico predictions for DTIs have largely depended on structural information of both targets and compounds, e.g., docking or ligand-based virtual screening. Recently, the application of deep neural network (DNN) is opening a new path to uncover novel DTIs for thousands of targets. One important question is which features for targets are most relevant to DTI prediction. As an early attempt to answer this question, we objectively compared three canonical target features extracted from: (i) the expression profiles by gene knockdown (GEPs); (ii) the protein-protein interaction network (PPI network); and (iii) the pathway membership (PM) of a target gene. For drug features, the large-scale drug-induced transcriptome dataset, or the Library of Integrated Network-based Cellular Signatures (LINCS) L1000 dataset was used. All these features are closely related to protein function or drug MoA, of which utility is only sparsely investigated. In particular, few studies have compared the three types of target features in DNN-based DTI prediction under the same evaluation scheme. Among the three target features, the PM and the PPI network show similar performances superior to GEPs. DNN models based on both features consistently outperformed other machine learning methods such as naïve Bayes, random forest, or logistic regression.

SUBMITTER: Lee H

PROVIDER: S-EPMC6723794 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Comparison of Target Features for Predicting Drug-Target Interactions by Deep Neural Network Based on Large-Scale Drug-Induced Transcriptome Data.

Lee Hanbi H Kim Wankyu W

Pharmaceutics 20190802 8

Uncovering drug-target interactions (DTIs) is pivotal to understand drug mode-of-action (MoA), avoid adverse drug reaction (ADR), and seek opportunities for drug repositioning (DR). For decades, in silico predictions for DTIs have largely depended on structural information of both targets and compounds, e.g., docking or ligand-based virtual screening. Recently, the application of deep neural network (DNN) is opening a new path to uncover novel DTIs for thousands of targets. One important questio ...[more]

PMID: 31382356

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Project description:MotivationIn silico prediction of drug-target interactions plays an important role toward identifying and developing new uses of existing or abandoned drugs. Network-based approaches have recently become a popular tool for discovering new drug-target interactions (DTIs). Unfortunately, most of these network-based approaches can only predict binary interactions between drugs and targets, and information about different types of interactions has not been well exploited for DTI prediction in previous studies. On the other hand, incorporating additional information about drug-target relationships or drug modes of action can improve prediction of DTIs. Furthermore, the predicted types of DTIs can broaden our understanding about the molecular basis of drug action.ResultsWe propose a first machine learning approach to integrate multiple types of DTIs and predict unknown drug-target relationships or drug modes of action. We cast the new DTI prediction problem into a two-layer graphical model, called restricted Boltzmann machine, and apply a practical learning algorithm to train our model and make predictions. Tests on two public databases show that our restricted Boltzmann machine model can effectively capture the latent features of a DTI network and achieve excellent performance on predicting different types of DTIs, with the area under precision-recall curve up to 89.6. In addition, we demonstrate that integrating multiple types of DTIs can significantly outperform other predictions either by simply mixing multiple types of interactions without distinction or using only a single interaction type. Further tests show that our approach can infer a high fraction of novel DTIs that has been validated by known experiments in the literature or other databases. These results indicate that our approach can have highly practical relevance to DTI prediction and drug repositioning, and hence advance the drug discovery process.AvailabilitySoftware and datasets are available on request.Supplementary informationSupplementary data are available at Bioinformatics online.

Dataset Information

Comparison of Target Features for Predicting Drug-Target Interactions by Deep Neural Network Based on Large-Scale Drug-Induced Transcriptome Data.

Publications

Comparison of Target Features for Predicting Drug-Target Interactions by Deep Neural Network Based on Large-Scale Drug-Induced Transcriptome Data.

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