Outcome of IWGT workshop on transcriptomic biomarkers for genotoxicity: Key considerations for bioinformatics.

Autor: Meier MJ; Environmental Health, Science and Research Bureau, Health Canada, Ottawa, Ontario, Canada., Caiment F; Department of Translational Genomics, GROW Research Institute for Oncology and Reproduction, Maastricht University, Maastricht, The Netherlands., Corton JC; Center for Computational Toxicology and Exposure, US-EPA, Research Triangle Park, North Carolina, USA., Frötschl R; BfArM-Bundesinstitut für Arzneimittel und Medizinprodukte, Federal Institute for Drugs and Medical Devices, Bonn, Germany., Fujita Y; Institute for Protein Research, Osaka University, Osaka, Japan., Jennen D; Department of Translational Genomics, GROW Research Institute for Oncology and Reproduction, Maastricht University, Maastricht, The Netherlands., Mezencev R; Center for Public Health and Environmental Assessment, Office of Research and Development, US EPA, Washington, DC, USA., Yauk C; Department of Biology, Faculty of Science, University of Ottawa, Ottawa, Ontario, Canada.
Jazyk: angličtina
Zdroj: Environmental and molecular mutagenesis [Environ Mol Mutagen] 2024 Dec 16. Date of Electronic Publication: 2024 Dec 16.
DOI: 10.1002/em.22644
Abstrakt: As a part of the International Workshop on Genotoxicity Testing (IWGT) in 2022, a workgroup was formed to evaluate the level of validation and regulatory acceptance of transcriptomic biomarkers that identify genotoxic substances. Several such biomarkers have been developed using various molecular techniques and computational approaches. Within the IWGT workgroup on transcriptomic biomarkers, bioinformatics was a central topic of discussion, focusing on the current approaches used to process the underlying molecular data to distill a reliable predictive signal; that is, a gene set that is indicative of genotoxicity and can then be used in later studies to predict potential DNA damaging properties for uncharacterized chemicals. While early studies used microarray data, a technological shift occurred in the past decade to incorporate modern transcriptome measuring techniques such as high-throughput transcriptomics, which in turn is based on high-throughput sequencing. Herein, we present the workgroup's review of the current bioinformatic approaches to identify genes comprising transcriptomic biomarkers. Within the context of regulatory toxicology, the reproducibility of a given analysis is critical. Therefore, the workgroup provides consensus recommendations on how to facilitate sufficient reporting of experimental parameters for the analytical procedures used in a transcriptomic biomarker study, including the recommendation to develop a biomarker-specific reporting module within the OECD Omics Reporting Framework.
(© 2024 His Majesty the King in Right of Canada and The Author(s). Environmental and Molecular Mutagenesis published by Wiley Periodicals LLC on behalf of Environmental Mutagenesis and Genomics Society. Reproduced with the permission of the Minister of Minister of Health. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)
Databáze: MEDLINE
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