MoS-TEC: A toxicogenomics database based on model selection for time-expression curves

Abstract

MoS-TEC is a newly developed toxicogenomics database for time-expression curves fitted with a statistical model selection approach. Toxicogenomic data provide information on the response of the genome to compounds, often measured in terms of gene expression values. When such experimental data are available for different exposure times, the functional relationships between the exposure time and the expression values of genes might be of interest. The TG-GATEs (Open Toxicogenomics Project-Genomics Assisted Toxicity Evaluation System) database provides such information for genomewide gene expression data for 170 compounds. We performed extensive model selection using MCP-Mod on these data. Specifically, gene expression data measured for eight time points from in vivo experiments on rat liver for 120 compounds with complete datasets were considered. MCP-Mod is a two-step approach, including a multiple comparison procedure (MCP) and a modelling (Mod) approach. The results are estimated time-expression curves that model the relationship between exposure time and gene expression values for all combinations of genes and compounds. We present an appropriate data normalization approach and report which models were selected per compound and in total. For high-quality model fits with a large value for the explained variance, the sigEmax model was most frequently selected. The new R Shiny application MoS-TEC provides easy access for researchers to the best curve fit for all genes individually for all compounds. It can be used online without installing additional software.