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Deep Modeling of Regulating Effects of Small Molecules on Longevity-Associated Genes

Aging is considered an inevitable process that causes deleterious effects in the functioning and appearance of cells, tissues, and organs. Recent emergence of large-scale gene expression datasets and significant advances in machine learning techniques have enabled drug repurposing efforts in promoti...

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Autores principales: You, Jiaying, Hsing, Michael, Cherkasov, Artem
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8539656/
https://www.ncbi.nlm.nih.gov/pubmed/34681172
http://dx.doi.org/10.3390/ph14100948
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author You, Jiaying
Hsing, Michael
Cherkasov, Artem
author_facet You, Jiaying
Hsing, Michael
Cherkasov, Artem
author_sort You, Jiaying
collection PubMed
description Aging is considered an inevitable process that causes deleterious effects in the functioning and appearance of cells, tissues, and organs. Recent emergence of large-scale gene expression datasets and significant advances in machine learning techniques have enabled drug repurposing efforts in promoting longevity. In this work, we further developed our previous approach—DeepCOP, a quantitative chemogenomic model that predicts gene regulating effects, and extended its application across multiple cell lines presented in LINCS to predict aging gene regulating effects induced by small molecules. As a result, a quantitative chemogenomic Deep Model was trained using gene ontology labels, molecular fingerprints, and cell line descriptors to predict gene expression responses to chemical perturbations. Other state-of-the-art machine learning approaches were also evaluated as benchmarks. Among those, the deep neural network (DNN) classifier has top-ranked known drugs with beneficial effects on aging genes, and some of these drugs were previously shown to promote longevity, illustrating the potential utility of this methodology. These results further demonstrate the capability of “hybrid” chemogenomic models, incorporating quantitative descriptors from biomarkers to capture cell specific drug–gene interactions. Such models can therefore be used for discovering drugs with desired gene regulatory effects associated with longevity.
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spelling pubmed-85396562021-10-24 Deep Modeling of Regulating Effects of Small Molecules on Longevity-Associated Genes You, Jiaying Hsing, Michael Cherkasov, Artem Pharmaceuticals (Basel) Article Aging is considered an inevitable process that causes deleterious effects in the functioning and appearance of cells, tissues, and organs. Recent emergence of large-scale gene expression datasets and significant advances in machine learning techniques have enabled drug repurposing efforts in promoting longevity. In this work, we further developed our previous approach—DeepCOP, a quantitative chemogenomic model that predicts gene regulating effects, and extended its application across multiple cell lines presented in LINCS to predict aging gene regulating effects induced by small molecules. As a result, a quantitative chemogenomic Deep Model was trained using gene ontology labels, molecular fingerprints, and cell line descriptors to predict gene expression responses to chemical perturbations. Other state-of-the-art machine learning approaches were also evaluated as benchmarks. Among those, the deep neural network (DNN) classifier has top-ranked known drugs with beneficial effects on aging genes, and some of these drugs were previously shown to promote longevity, illustrating the potential utility of this methodology. These results further demonstrate the capability of “hybrid” chemogenomic models, incorporating quantitative descriptors from biomarkers to capture cell specific drug–gene interactions. Such models can therefore be used for discovering drugs with desired gene regulatory effects associated with longevity. MDPI 2021-09-22 /pmc/articles/PMC8539656/ /pubmed/34681172 http://dx.doi.org/10.3390/ph14100948 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
You, Jiaying
Hsing, Michael
Cherkasov, Artem
Deep Modeling of Regulating Effects of Small Molecules on Longevity-Associated Genes
title Deep Modeling of Regulating Effects of Small Molecules on Longevity-Associated Genes
title_full Deep Modeling of Regulating Effects of Small Molecules on Longevity-Associated Genes
title_fullStr Deep Modeling of Regulating Effects of Small Molecules on Longevity-Associated Genes
title_full_unstemmed Deep Modeling of Regulating Effects of Small Molecules on Longevity-Associated Genes
title_short Deep Modeling of Regulating Effects of Small Molecules on Longevity-Associated Genes
title_sort deep modeling of regulating effects of small molecules on longevity-associated genes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8539656/
https://www.ncbi.nlm.nih.gov/pubmed/34681172
http://dx.doi.org/10.3390/ph14100948
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