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Related Concept Videos

DNA Microarrays02:34

DNA Microarrays

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Microarrays are high-throughput and relatively inexpensive assays that can be automated to analyze large quantities of data at a time. They are used in genome-wide studies to compare gene or protein expression under two varied conditions, such as healthy and diseased states. Microarrays consist of glass or silica slides on which probe molecules are covalently attached through surface functionalization. Most commonly, the slides are prepared through the chemisorption of silanes to silica...
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Array Comparative Genomic Hybridization Array CGH for Detection of Genomic Copy Number Variants
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RAID: Regression Analysis-Based Inductive DNA Microarray for Precise Read-Across.

Yuto Amano1, Masayuki Yamane1, Hiroshi Honda1

  • 1R&D Safety Science Research, Kao Corporation, Tochigi, Japan.

Frontiers in Pharmacology
|August 8, 2022
PubMed
Summary

A new virtual DNA microarray, Regression Analysis-based Inductive DNA microarray (RAID), predicts in vivo gene expression from chemical structures and in vitro data. This method refines toxicity assessments and supports animal testing alternatives.

Keywords:
alternative methodgene expression analysishepatotoxicitynew approach methodologyoligonucleotide array

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Area of Science:

  • Toxicology
  • Computational Chemistry
  • Genomics

Background:

  • Chemical structure-based read-across is promising for toxicity evaluation but lacks direct in vivo correlation.
  • In vitro studies for read-across refinement face external validity challenges due to in vitro-in vivo condition gaps.

Purpose of the Study:

  • To develop a virtual DNA microarray system (RAID) for quantitative prediction of in vivo gene expression profiles.
  • To enable in vitro to in vivo extrapolation (IVIVE) using chemical structure and in vitro transcriptome data.

Main Methods:

  • Elastic-net models were built for each gene using chemical descriptors and in vitro transcriptome data to predict in vivo data.
  • Feature selection identified genes crucial for quantitative structure-activity relationship (QSAR) and IVIVE.
  • RAID was validated by predicting and analyzing gene expression profiles of hepatotoxic substances.

Main Results:

  • Predicted transcriptome data from RAID accurately reflected in vivo gene expression profiles of hepatotoxic substances.
  • Gene ontology and pathway analyses revealed links to nuclear receptor-mediated xenobiotic response and metabolic activation.
  • Identified IVIVE-related genes were associated with key metabolic pathways, confirming in vitro study effectiveness for these events.

Conclusions:

  • The RAID system offers a viable alternative screening test for repeated-dose toxicity and toxicogenomics.
  • RAID provides a critical solution for IVIVE-based read-across by integrating mode of action and chemical structures.
  • This approach advances non-animal testing methods in chemical safety assessment.