Gene expression analysis of livers from female B6C3F1 mice exposed to carcinogenic and non-carcinogenic doses of furan, with or without bromodeoxyuridine (BrdU) treatment
- DOI
- Language of the publication
- English
- Date
- 2014-06-11
- Type
- Article
- Author(s)
- Webster, Anna Francina
- Williams, Andrew
- Recio, Leslie
- Yauk, Carole L.
- Publisher
- Elsevier
Abstract
Standard methodology for identifying chemical carcinogens is both time-consuming and resource intensive. Researchers are actively investigating how new technologies can be used to identify chemical carcinogens in a more rapid and cost-effective manner. Here we performed a toxicogenomic case study of the liver carcinogen furan. Full study and mode of action details were previously published in the Journal of Toxicology and Applied Pharmacology. Female B6C3F1 mice were sub-chronically treated with two non-carcinogenic (1 and 2 mg/kg bw) and two carcinogenic (4 and 8 mg/kg bw) doses of furan for 21 days. Half of the mice in each dose group were also treated with 0.02% bromodeoxyuridine (BrdU) for five days prior to sacrifice [13]. Agilent gene expression microarrays were used to measure changes in liver gene and long non-coding RNA expression (published in Toxicological Sciences). Here we describe the experimental and quality control details for the microarray data. We also provide the R code used to analyze the raw data files, produce fold change and false discovery rate (FDR) adjusted p values for each gene, and construct hierarchical clustering between datasets.
Plain language summary
Health Canada previously conducted a case study to better understand how modern genomics technologies could be used to inform risk assessment approaches, which was published in 2014 in the journal Toxicology and Applied Pharmacology. In that study, the response of all of the genes in the mouse liver to the model chemical furan, a known rodent liver carcinogen, was investigated. Modern genomics technologies were used to understand what biological changes are brought about by furan on liver cells at a molecular level. However, these genomics technologies produce a large amount of data. Analysis of ‘big data’ can be very complex and is often inadequately explained in standard journal articles, which are often not oriented to present an in-depth explanation of the analytical tools used (including computer code and complex statistics) that would allow others to use and build upon the results. In this follow-up methods paper, a detailed description is provided of the biostatistics and bioinformatics approaches that were used to analyze this large dataset. Since ‘big data’ can be used and reused by researchers to answer many different scientific questions, in addition to making the data accessible, it is very important to provide guidance on techniques for their proper analysis. This paper is an example of how Health Canada has adopted the ‘Minimum Information about a Microarray Experiment’ (MIAME) guidelines to make big data publically available and promote their use for the benefit of the broader scientific community.
Subject
- Health,
- Health and safety