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About the Authors:
B. Alex Merrick
* E-mail: [email protected]
Affiliation: Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, United States of America
Dhiral P. Phadke
Affiliation: Systems Research and Applications International, Durham, North Carolina, United States of America
Scott S. Auerbach
Affiliation: Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, United States of America
Deepak Mav
Affiliation: Systems Research and Applications International, Durham, North Carolina, United States of America
Suzy M. Stiegelmeyer
Affiliation: Systems Research and Applications International, Durham, North Carolina, United States of America
Ruchir R. Shah
Affiliation: Systems Research and Applications International, Durham, North Carolina, United States of America
Raymond R. Tice
Affiliation: Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, United States of America
Introduction
Deep sequencing technologies provide unprecedented coverage of the transcriptome at nucleotide resolution and a wide dynamic range compared to hybridization microarrays based upon predefined probes [1], [2]. RNA-Seq offers the potential for de novo definition of intron-exon boundaries, 5′- and 3′-untranslated regions, splice variants, single nucleotide polymorphisms (SNPs), and potentially new transcripts at a highly accurate level of quantitation, all of which are crucial for the analysis of differential gene expression [3], [4], [5]. The laboratory rat is an important experimental animal model for the study of chemically-induced diseases but RNA-Seq studies of rat tissues [6], [7], [8], [9], [10], [11] are still rather limited in part because its complete genomic sequence and annotation are still being refined [12], [13]. Published rat transcript profiling studies have focused on effects in the ageing cerebral cortex [10], neurons in the nucleus accumbens [6], the hippocampus of alcohol-addicted rats [7], functional compartments in the rat placentation site [9], the ventricular myocardium from SHR rats, [8] and kidneys from aristolochic acid exposed animals [14]. Recent studies suggest that RNA-Seq is comparable to and provides a greater level of transcriptional detail than genome-wide microarrays, particularly for detecting low copy transcripts and that it provides for an overall higher dynamic range of signal intensity at 2 to 3 orders of magnitude greater than microarrays [14], [15].
Global gene expression studies using RNA-Seq can provide insights into...