A Systems Toxicology Approach To Understanding Drug Toxicity And Compound Prioritization

Presented by:
Kevin T. Morgan, Old Dogs in Training, LLC
Ke Xu, Department of Pharmacology, UNC Chapel Hill

Sound decisions require sound knowledge. Whilst drowning in a swelling sea of information, we are given little time for the reflective contemplation needed to derive knowledge from this information. Epistemology, which concerns itself with the origins and nature of knowledge, indicates that the nature of knowledge itself is influenced by our information-generating technologies (Postman N, 1986, "Amusing Ourselves To Death"). Once again, we are feeling the impact of new technologies on the process of knowledge generation in the form 'omics' information overload! For instance, Transcriptomics requires the interpretation of large-scale transcriptional responses to a range of physiological variables, including toxic chemicals (Toxicogenomics). Both Transcriptomics and Toxicogenomics, which have been used for decades, are contributing to information overload at an accelerating rate. The interpretation of large-scale gene expression data requires a broad general understanding of biological systems, a feel for the dynamics of networks and their embedded pathways, plus the availability of appropriate analytical software and time to think without interruption. Unfortunately, in spite of a massive investment in omics technologies (hardware and software), most Toxicogenomic studies receive inadequate interpretation due to (a) insufficient training of staff (wetware) in transcriptome physiology and pathophysiology, and (b) inadequate allocation of trained wetware resources to the task. The need for structured education in this field will be discussed in relation to Bioenergetics, Dynamics, and type II diabetes drug targets, through the application of Array Studio and IPA® software to publicly available datasets.