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RAID: Regression Analysis–Based Inductive DNA Microarray for Precise Read-Across
Chemical structure-based read-across represents a promising method for chemical toxicity evaluation without the need for animal testing; however, a chemical structure is not necessarily related to toxicity. Therefore, in vitro studies were often used for read-across reliability refinement; however,...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354856/ https://www.ncbi.nlm.nih.gov/pubmed/35935858 http://dx.doi.org/10.3389/fphar.2022.879907 |
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author | Amano, Yuto Yamane, Masayuki Honda, Hiroshi |
author_facet | Amano, Yuto Yamane, Masayuki Honda, Hiroshi |
author_sort | Amano, Yuto |
collection | PubMed |
description | Chemical structure-based read-across represents a promising method for chemical toxicity evaluation without the need for animal testing; however, a chemical structure is not necessarily related to toxicity. Therefore, in vitro studies were often used for read-across reliability refinement; however, their external validity has been hindered by the gap between in vitro and in vivo conditions. Thus, we developed a virtual DNA microarray, regression analysis–based inductive DNA microarray (RAID), which quantitatively predicts in vivo gene expression profiles based on the chemical structure and/or in vitro transcriptome data. For each gene, elastic-net models were constructed using chemical descriptors and in vitro transcriptome data to predict in vivo data from in vitro data (in vitro to in vivo extrapolation; IVIVE). In feature selection, useful genes for assessing the quantitative structure–activity relationship (QSAR) and IVIVE were identified. Predicted transcriptome data derived from the RAID system reflected the in vivo gene expression profiles of characteristic hepatotoxic substances. Moreover, gene ontology and pathway analysis indicated that nuclear receptor-mediated xenobiotic response and metabolic activation are related to these gene expressions. The identified IVIVE-related genes were associated with fatty acid, xenobiotic, and drug metabolisms, indicating that in vitro studies were effective in evaluating these key events. Furthermore, validation studies revealed that chemical substances associated with these key events could be detected as hepatotoxic biosimilar substances. These results indicated that the RAID system could represent an alternative screening test for a repeated-dose toxicity test and toxicogenomics analyses. Our technology provides a critical solution for IVIVE-based read-across by considering the mode of action and chemical structures. |
format | Online Article Text |
id | pubmed-9354856 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-93548562022-08-06 RAID: Regression Analysis–Based Inductive DNA Microarray for Precise Read-Across Amano, Yuto Yamane, Masayuki Honda, Hiroshi Front Pharmacol Pharmacology Chemical structure-based read-across represents a promising method for chemical toxicity evaluation without the need for animal testing; however, a chemical structure is not necessarily related to toxicity. Therefore, in vitro studies were often used for read-across reliability refinement; however, their external validity has been hindered by the gap between in vitro and in vivo conditions. Thus, we developed a virtual DNA microarray, regression analysis–based inductive DNA microarray (RAID), which quantitatively predicts in vivo gene expression profiles based on the chemical structure and/or in vitro transcriptome data. For each gene, elastic-net models were constructed using chemical descriptors and in vitro transcriptome data to predict in vivo data from in vitro data (in vitro to in vivo extrapolation; IVIVE). In feature selection, useful genes for assessing the quantitative structure–activity relationship (QSAR) and IVIVE were identified. Predicted transcriptome data derived from the RAID system reflected the in vivo gene expression profiles of characteristic hepatotoxic substances. Moreover, gene ontology and pathway analysis indicated that nuclear receptor-mediated xenobiotic response and metabolic activation are related to these gene expressions. The identified IVIVE-related genes were associated with fatty acid, xenobiotic, and drug metabolisms, indicating that in vitro studies were effective in evaluating these key events. Furthermore, validation studies revealed that chemical substances associated with these key events could be detected as hepatotoxic biosimilar substances. These results indicated that the RAID system could represent an alternative screening test for a repeated-dose toxicity test and toxicogenomics analyses. Our technology provides a critical solution for IVIVE-based read-across by considering the mode of action and chemical structures. Frontiers Media S.A. 2022-07-22 /pmc/articles/PMC9354856/ /pubmed/35935858 http://dx.doi.org/10.3389/fphar.2022.879907 Text en Copyright © 2022 Amano, Yamane and Honda. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Amano, Yuto Yamane, Masayuki Honda, Hiroshi RAID: Regression Analysis–Based Inductive DNA Microarray for Precise Read-Across |
title | RAID: Regression Analysis–Based Inductive DNA Microarray for Precise Read-Across |
title_full | RAID: Regression Analysis–Based Inductive DNA Microarray for Precise Read-Across |
title_fullStr | RAID: Regression Analysis–Based Inductive DNA Microarray for Precise Read-Across |
title_full_unstemmed | RAID: Regression Analysis–Based Inductive DNA Microarray for Precise Read-Across |
title_short | RAID: Regression Analysis–Based Inductive DNA Microarray for Precise Read-Across |
title_sort | raid: regression analysis–based inductive dna microarray for precise read-across |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354856/ https://www.ncbi.nlm.nih.gov/pubmed/35935858 http://dx.doi.org/10.3389/fphar.2022.879907 |
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