Project description:Evaluating the potential human health and ecological risks associated with exposures to complex chemical mixtures in the environment is one of the main challenges of chemical safety assessment and environmental protection. There is a need for approaches that can help to integrate chemical monitoring and biological effects data to evaluate risks associated with specific chemicals present in the environment. In the present study water samples from five locations near two wastewater treatment plants in the St. Croix River basin on the border of MN and WI, USA were analyzed for 127 contaminants including wastewater indicators, pharmaceuticals, and a number of natural and synthetic steroids. Prior knowledge about chemical-gene interactions was used to develop site-specific knowledge assembly models (KAMs) that were used to formulate hypothesis concerning possible biological effects of exposure to the chemicals detected at each location and suggest assays and endpoints for follow-up investigation. Additionally empirical hepatic gene expression data were collected for fathead minnows (Pimephales promelas) exposed in situ, for 12 d, at each location using a high density oligonucleotide microarray. Empirical gene expression data were analyzed to identify functional annotation terms enriched among the lists of differentially-expressed probes. However, the general nature of many of the terms made hypothesis formulation on the basis of the transcriptome-level response alone difficult. However, integrated analysis of the transcriptome data in the context of the site-specific KAMs allowed for evaluation of the likelihood of specific chemicals contributing to observed biological responses, based on prior knowledge.