Open TG-GATEs: a large-scale toxicogenomics database.
Bottom Line: Gene expression signatures from large toxicogenomics databases are expected to perform better than small databases in identifying biomarkers for the prediction and evaluation of drug safety based on a compound's toxicological mechanisms in animal target organs.Over the past 10 years, the Japanese Toxicogenomics Project consortium (TGP) has been developing a large-scale toxicogenomics database consisting of data from 170 compounds (mostly drugs) with the aim of improving and enhancing drug safety assessment.Here, we provide a comprehensive overview of the database, including both gene expression data and metadata, with a description of experimental conditions and procedures used to generate the database.
Affiliation: Toxicogenomics Informatics Project, National Institute of Biomedical Innovation, Osaka 567-0085, Japan.Show MeSH
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Mentions: The experimental procedures for the animal studies have been described previously (7,8) and are summarized here in brief. Animal experiments were conducted by four different contract research organizations. The studies used male Crl:CD Sprague-Dawley (SD) rats purchased from Charles River Japan, Inc. (Hino or Atsugi, Japan) as 5-week-old animals. After a 7-day quarantine and acclimatization period, the animals were allocated into groups of 20 animals each using a computerized stratified random grouping method based on body weight. Each animal was allowed free access to water and pelleted food (radiation-sterilized CRF-1; Oriental Yeast Co., Tokyo, Japan). For single-dose experiments, groups of 20 animals were administered a compound and then fivw animals/time point were sacrificed at 3, 6, 9 or 24 h after administration. For repeated-dose experiments, groups of 20 animals received a single dose per day of a compound and five animals/time point were sacrificed at 4, 8, 15 or 29 days (i.e. 24 h after the respective final administration at 3, 7, 14 or 28 days) (Figure 3). Animals were not fasted before being sacrificed. To avoid effects of diurnal cycling, the animals were sacrificed and necropsies were performed between 9:00 a.m. and 11:00 a.m. for the repeated-dose studies. Blood samples for routine biochemical analyses were collected into heparinized tubes under ether anesthesia from the abdominal aorta at the time of sacrifice.
Affiliation: Toxicogenomics Informatics Project, National Institute of Biomedical Innovation, Osaka 567-0085, Japan.