{"title":"Integrating gene expression biomarker predictions into networks of adverse outcome pathways","authors":"J. Christopher Corton","doi":"10.1016/j.cotox.2019.05.006","DOIUrl":null,"url":null,"abstract":"<div><p>Microarray profiling in the context of toxicity testing in animals has been used for years to identify mechanisms of toxicity, derive points of departure using dose–response modeling, and determine human relevance. High-throughput transcriptomic technologies are increasingly being used to screen environmental chemicals in vitro to identify molecular targets and provide mechanistic context for regulatory testing. This review will discuss the use of gene expression biomarkers to make predictions of activity of molecular targets of chemicals that can be linked to adverse outcomes in a number of cellular and tissue contexts. Gene expression biomarkers are built using global gene expression comparisons from cells or tissues exposed to chemicals with known effects on the factor of interest. Incorporating profiles in which the expression of the factor is altered (e.g. in gene-null mice) facilitates the identification of predictive genes. As an example of their use, biomarkers that predict molecular initiating events and key events in liver cancer adverse outcome pathways have been shown to accurately identify chemical–dose combinations in short-term studies that lead to liver cancer in 2-year bioassays. In the near future, batteries of biomarkers that predict modulation of important targets of environmental chemicals could be used to interpret high-throughput transcriptomic screening data.</p></div>","PeriodicalId":37736,"journal":{"name":"Current Opinion in Toxicology","volume":"18 ","pages":"Pages 54-61"},"PeriodicalIF":6.1000,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cotox.2019.05.006","citationCount":"4","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Opinion in Toxicology","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2468202019300099","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"TOXICOLOGY","Score":null,"Total":0}
引用次数: 4
Abstract
Microarray profiling in the context of toxicity testing in animals has been used for years to identify mechanisms of toxicity, derive points of departure using dose–response modeling, and determine human relevance. High-throughput transcriptomic technologies are increasingly being used to screen environmental chemicals in vitro to identify molecular targets and provide mechanistic context for regulatory testing. This review will discuss the use of gene expression biomarkers to make predictions of activity of molecular targets of chemicals that can be linked to adverse outcomes in a number of cellular and tissue contexts. Gene expression biomarkers are built using global gene expression comparisons from cells or tissues exposed to chemicals with known effects on the factor of interest. Incorporating profiles in which the expression of the factor is altered (e.g. in gene-null mice) facilitates the identification of predictive genes. As an example of their use, biomarkers that predict molecular initiating events and key events in liver cancer adverse outcome pathways have been shown to accurately identify chemical–dose combinations in short-term studies that lead to liver cancer in 2-year bioassays. In the near future, batteries of biomarkers that predict modulation of important targets of environmental chemicals could be used to interpret high-throughput transcriptomic screening data.
期刊介绍:
The aims and scope of Current Opinion in Toxicology is to systematically provide the reader with timely and provocative views and opinions of the highest qualified and recognized experts on current advances in selected topics within the field of toxicology. The goal is that Current Opinion in Toxicology will be an invaluable source of information and perspective for researchers, teachers, managers and administrators, policy makers and students. Division of the subject into sections: For this purpose, the scope of Toxicology is divided into six selected high impact themed sections, each of which is reviewed once a year: Mechanistic Toxicology, Metabolic Toxicology, Risk assessment in Toxicology, Genomic Toxicology, Systems Toxicology, Translational Toxicology.