Application of transcriptomic data, visualization tools and bioinformatics resources for informing mode of action

Gene expression analyses have proved useful for assessing modes of action (MOAs) with various compounds both following in life exposures to intact animals and in vitro exposures of cells in culture. Various tools have been used/developed over the past decade or so to assist in the analysis of these patterns of differential gene expression - heatmaps, pathway enrichment analysis, benchmark dose estimations and network representations of affected pathways using different ontologies. MOAs assessed from using these gene expression results sometimes have confirmed expectations from conventional toxicity testing and sometimes proved divergent, giving a more comprehensive look at the affected biology with compounds such as styrene or dichloromethane. This chapter discusses modes of action inferred from gene expression studies in relation to dose response modeling, dose-dependent transitions, pathway perturbations and comparing results from one treatment condition with another. Our expectation from even the limited experience to date with differential gene expression for evaluating MOAs is that the continuing application of these tools to both in vivo and in vitro patterns of gene expression will uncover subtle differences in response among even similar compounds and also provide new tools for assessing the biological consequences of exposures to bioactive compounds.