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Prediction of Potential Drug–Disease Associations through Deep Integration of Diversity and Projections of Various Drug Features

Identifying new indications for existing drugs may reduce costs and expedites drug development. Drug-related disease predictions typically combined heterogeneous drug-related and disease-related data to derive the associations between drugs and diseases, while recently developed approaches integrate...

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Autores principales: Xuan, Ping, Song, Yingying, Zhang, Tiangang, Jia, Lan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6747548/
https://www.ncbi.nlm.nih.gov/pubmed/31443472
http://dx.doi.org/10.3390/ijms20174102
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author Xuan, Ping
Song, Yingying
Zhang, Tiangang
Jia, Lan
author_facet Xuan, Ping
Song, Yingying
Zhang, Tiangang
Jia, Lan
author_sort Xuan, Ping
collection PubMed
description Identifying new indications for existing drugs may reduce costs and expedites drug development. Drug-related disease predictions typically combined heterogeneous drug-related and disease-related data to derive the associations between drugs and diseases, while recently developed approaches integrate multiple kinds of drug features, but fail to take the diversity implied by these features into account. We developed a method based on non-negative matrix factorization, DivePred, for predicting potential drug–disease associations. DivePred integrated disease similarity, drug–disease associations, and various drug features derived from drug chemical substructures, drug target protein domains, drug target annotations, and drug-related diseases. Diverse drug features reflect the characteristics of drugs from different perspectives, and utilizing the diversity of multiple kinds of features is critical for association prediction. The various drug features had higher dimensions and sparse characteristics, whereas DivePred projected high-dimensional drug features into the low-dimensional feature space to generate dense feature representations of drugs. Furthermore, DivePred’s optimization term enhanced diversity and reduced redundancy of multiple kinds of drug features. The neighbor information was exploited to infer the likelihood of drug–disease associations. Experiments indicated that DivePred was superior to several state-of-the-art methods for prediction drug-disease association. During the validation process, DivePred identified more drug-disease associations in the top part of prediction result than other methods, benefitting further biological validation. Case studies of acetaminophen, ciprofloxacin, doxorubicin, hydrocortisone, and ampicillin demonstrated that DivePred has the ability to discover potential candidate disease indications for drugs.
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spelling pubmed-67475482019-09-27 Prediction of Potential Drug–Disease Associations through Deep Integration of Diversity and Projections of Various Drug Features Xuan, Ping Song, Yingying Zhang, Tiangang Jia, Lan Int J Mol Sci Article Identifying new indications for existing drugs may reduce costs and expedites drug development. Drug-related disease predictions typically combined heterogeneous drug-related and disease-related data to derive the associations between drugs and diseases, while recently developed approaches integrate multiple kinds of drug features, but fail to take the diversity implied by these features into account. We developed a method based on non-negative matrix factorization, DivePred, for predicting potential drug–disease associations. DivePred integrated disease similarity, drug–disease associations, and various drug features derived from drug chemical substructures, drug target protein domains, drug target annotations, and drug-related diseases. Diverse drug features reflect the characteristics of drugs from different perspectives, and utilizing the diversity of multiple kinds of features is critical for association prediction. The various drug features had higher dimensions and sparse characteristics, whereas DivePred projected high-dimensional drug features into the low-dimensional feature space to generate dense feature representations of drugs. Furthermore, DivePred’s optimization term enhanced diversity and reduced redundancy of multiple kinds of drug features. The neighbor information was exploited to infer the likelihood of drug–disease associations. Experiments indicated that DivePred was superior to several state-of-the-art methods for prediction drug-disease association. During the validation process, DivePred identified more drug-disease associations in the top part of prediction result than other methods, benefitting further biological validation. Case studies of acetaminophen, ciprofloxacin, doxorubicin, hydrocortisone, and ampicillin demonstrated that DivePred has the ability to discover potential candidate disease indications for drugs. MDPI 2019-08-22 /pmc/articles/PMC6747548/ /pubmed/31443472 http://dx.doi.org/10.3390/ijms20174102 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Xuan, Ping
Song, Yingying
Zhang, Tiangang
Jia, Lan
Prediction of Potential Drug–Disease Associations through Deep Integration of Diversity and Projections of Various Drug Features
title Prediction of Potential Drug–Disease Associations through Deep Integration of Diversity and Projections of Various Drug Features
title_full Prediction of Potential Drug–Disease Associations through Deep Integration of Diversity and Projections of Various Drug Features
title_fullStr Prediction of Potential Drug–Disease Associations through Deep Integration of Diversity and Projections of Various Drug Features
title_full_unstemmed Prediction of Potential Drug–Disease Associations through Deep Integration of Diversity and Projections of Various Drug Features
title_short Prediction of Potential Drug–Disease Associations through Deep Integration of Diversity and Projections of Various Drug Features
title_sort prediction of potential drug–disease associations through deep integration of diversity and projections of various drug features
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6747548/
https://www.ncbi.nlm.nih.gov/pubmed/31443472
http://dx.doi.org/10.3390/ijms20174102
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