Pathway activity analysis for transcriptional profiling of in utero exposure to d-n-butyl phthalate
M.A. Ovacik1, M.G. Ierapetritou1, P.G. Georgopoulos2, W. Welsh2, S. Euling3, B. Sen,3 K. Gaido4, I.P. Androulakis1
1Rutgers University, 2UMDNJ, 3USEPA, 4CIIT
We explore the potential of using a toxicogenomics approach to assess potential implication of exposure to Di-butyl-phthalate (DBP). Previous transcriptional studies employed the most general approach; genes expression profiles are ranked based on their differential expression characteristics by using one of the various statistical methods and subsequent enrichment analysis identified relevant pathways. In this paper, we propose the use of the concept of pathway activity that considers gene expression in the context of pathway and its potential use in risk assessments. We examined DBP exposure data using two animal studies. These animal studies aimed at analyzing (i) a two-state (control vs. treated) and (ii) time exposure. The analysis determined a number of relevant and critical active pathways that have not been previously identified, such as Valine, Leucine and Isoleucine (VLI) degradation and Glutathione metabolism which take places in cholesterol biosynthesis and xenobiotics metabolism, respectively.