Open TG-GATEs: a large-scale toxicogenomics database

Abstract

Toxicogenomics focuses on assessing the safety of compounds using gene expression profiles. 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. Most of the data generated by the project (e.g. gene expression, pathology, lot number) are freely available to the public via Open TG-GATEs (Toxicogenomics Project-Genomics Assisted Toxicity Evaluation System). 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. Open TG-GATEs is available from http://toxico.nibio.go.jp/english/index.html.

Figure 1.

Open TG-GATEs offers hierarchical access from compound and pathology lists to hematology, biochemical parameters and digitized pathology images. Gene expression data are stored as CEL files, which require software capable of interacting with the Affymetrix data file format. Thus, users will have to convert the primary data into a general-purpose format using various algorithms such as MAS5.0, RMA, etc.

Figure 2.

The relationship of the databases and organizations are shown. The dotted line shows the data distribution. NIBIO: National Institute of Biomedical Innovation, TGP: Toxicogenomics project in Japan.

Figure 3.

Time lines summarizing the procedures used for in vivo studies of single- and repeated-dose toxicity. For the repeated-dose studies, only the final dose is shown.