title: Prior knowledge-based approach for associating contaminants with biological effects: A case study in the St. Croix River basin, MN, WI, USA.
abstract: Evaluating potential adverse effects of complex chemical mixtures in the environment is challenging. One way to address that challenge is through more integrated analysis of chemical monitoring and biological effects data. In the present study, water samples from five locations near two municipal wastewater treatment plants in the St. Croix River basin, on the border of MN and WI, USA, were analyzed for 127 organic contaminants. Known chemical-gene interactions were used to develop site-specific knowledge assembly models (KAMs) and formulate hypotheses concerning possible biological effects associated with chemicals detected in water samples from each location. Additionally, hepatic gene expression data were collected for fathead minnows (Pimephales promelas) exposed in situ, for 12 d, at each location. Expression data from oligonucleotide microarrays were analyzed to identify functional annotation terms enriched among the differentially-expressed probes. 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. Thirteen chemicals (atrazine, carbamazepine, metformin, thiabendazole, diazepam, cholesterol, p-cresol, phenytoin, omeprazole, ethyromycin, 17β-estradiol, cimetidine, and estrone), for which there was statistically significant concordance between occurrence at a site and expected biological response as represented in the KAM, were identified. While not definitive, the approach provides a line of evidence for evaluating potential cause-effect relationships between components of a complex mixture of contaminants and biological effects data, which can inform subsequent monitoring and investigation.
authors.affiliation: University of Minnesota - Twin Cities, Water Resources Center, 1985 Lower Buford Circle, St. Paul, MN 55108, USA; U.S. Environmental Protection Agency, National Health and Environmental Effects Research Laboratory, Duluth, MN 55804, USA.
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Schroeder
authors.affiliation: University of St. Thomas, Department of Biology, Mail OWS 390, 2115 Summit Ave, Saint Paul, MN 55105, USA.
authors.forename: Dalma
authors.initials: D
authors.lastname: Martinović-Weigelt
authors.affiliation: U.S. Environmental Protection Agency, National Health and Environmental Effects Research Laboratory, Duluth, MN 55804, USA.
authors.forename: Gerald T
authors.initials: GT
authors.lastname: Ankley
authors.affiliation: U.S. Geological Survey, Toxic Substances Hydrology Program, Grand Rapids, MN 55744, USA.
authors.forename: Kathy E
authors.initials: KE
authors.lastname: Lee
authors.affiliation: U.S. Army Engineer Research and Development Center - Environmental Laboratory, Vicksburg, MS 39180, USA; Mississippi State University - Institute for Genomics Biocomputing and Biotechnology, Starkville, MS 39762, USA.
authors.forename: Natalia
authors.initials: N
authors.lastname: Garcia-Reyero
authors.affiliation: U.S. Army Engineer Research and Development Center - Environmental Laboratory, Vicksburg, MS 39180, USA.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Perkins
authors.affiliation: Aquatic Toxicology Laboratory, WSB-273, St., Cloud State University, St. Cloud, MN 56301, USA.
authors.forename: Heiko L
authors.initials: HL
authors.lastname: Schoenfuss
authors.affiliation: U.S. Environmental Protection Agency, National Health and Environmental Effects Research Laboratory, Duluth, MN 55804, USA. Electronic address: Villeneuve.dan@epa.gov.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Villeneuve
mesh_terms: D000818:Animals; D003408:Cresols; D003530:Cyprinidae / Q000378:metabolism; D004784:Environmental Monitoring / Q000379:methods*; D004970:Estrone / Q000032:analysis; D015870:Gene Expression; D008910:Minnesota; D020411:Oligonucleotide Array Sequence Analysis; D045483:Rivers / Q000737:chemistry; D062065:Wastewater / Q000032:analysis; D014874:Water Pollutants, Chemical / Q000032:analysis / Q000633:toxicity*; D014922:Wisconsin
chemical_list: D003408:Cresols; D004970:Estrone; D062065:Wastewater; D014874:Water Pollutants, Chemical; C032538:4-cresol
keywords: Adverse outcome pathway; Chemical mixtures; Chemical-gene interactions; Comparative toxicogenomics database; Contaminants