抄録
ToxWiz is a comprehensive software and database system designed to help make decisions in toxicology and many other areas of drug discovery. This approach offers an unprecedented insight into understanding the connections between chemical structures, gene expression, protein networks and toxic or pharmacological end points. Better understanding of mechanisms allows us to make a more informed assessment of risk or benefit of a drug/chemical. Combining chemical structures, together with genomics, proteomics and a vast collection of annotated data from the scientific literature in the system are able to make accurate predictions of toxic endpoints or other aspects of pharmacology, and possibly associated mechanistic explanations, that can be easily visualized, and explored further.
These approaches allow toxicologist to analyze toxicities both in a prospective way (to predict) and retrospectively (to explain mechanisms of action of the observed toxicity). Both of these are explained on the case studies concerning the toxicity of phthalate derivatives. We examined a mouse liver microarray dataset for the well established toxin, phthalate. We also investigate the chemical itself, by way of a substructure search, and compare the results with those that we get from the microarray. This analysis demonstrates one of the many ways in which ToxWiz shows how by combining microarray data with the chemical information in the system it is possible to gain insights into possible mechanisms of toxicity.
