title: Compendium of TCDD-mediated transcriptomic response datasets in mammalian model systems.
abstract: 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is the most potent congener of the dioxin class of environmental contaminants. Exposure to TCDD causes a wide range of toxic outcomes, ranging from chloracne to acute lethality. The severity of toxicity is highly dependent on the aryl hydrocarbon receptor (AHR). Binding of TCDD to the AHR leads to changes in transcription of numerous genes. Studies evaluating the transcriptional changes brought on by TCDD may provide valuable insight into the role of the AHR in human health and disease. We therefore compiled a collection of transcriptomic datasets that can be used to aid the scientific community in better understanding the transcriptional effects of ligand-activated AHR.
  
  
  
  Specifically, we have created a datasets package - TCDD.Transcriptomics - for the R statistical environment, consisting of 63 unique experiments comprising 377 samples, including various combinations of 3 species (human derived cell lines, mouse and rat), 4 tissue types (liver, kidney, white adipose tissue and hypothalamus) and a wide range of TCDD exposure times and doses. These datasets have been fully standardized using consistent preprocessing and annotation packages (available as of September 14, 2015). To demonstrate the utility of this R package, a subset of "AHR-core" genes were evaluated across the included datasets. Ahrr, Nqo1 and members of the Cyp family were significantly induced following exposure to TCDD across the studies as expected while Aldh3a1 was induced specifically in rat liver. Inmt was altered only in liver tissue and primarily by rat-AHR.
  
  
  
  Analysis of the "AHR-core" genes demonstrates a continued need for studies surrounding the impact of AHR-activity on the transcriptome; genes believed to be consistently regulated by ligand-activated AHR show surprisingly little overlap across species and tissues. Until now, a comprehensive assessment of the transcriptome across these studies was challenging due to differences in array platforms, processing methods and annotation versions. We believe that this package, which is freely available for download ( http://labs.oicr.on.ca/boutros-lab/tcdd-transcriptomics ) will prove to be a highly beneficial resource to the scientific community evaluating the effects of TCDD exposure as well as the variety of functions of the AHR.
authors.affiliation: Informatics and Bio-computing Program, Ontario Institute for Cancer Research, 661 University Avenue, Suite 510, Toronto, ON, M5G 0A3, Canada.
authors.forename: Stephenie D
authors.initials: SD
authors.lastname: Prokopec
authors.affiliation: Informatics and Bio-computing Program, Ontario Institute for Cancer Research, 661 University Avenue, Suite 510, Toronto, ON, M5G 0A3, Canada.
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Houlahan
authors.affiliation: Informatics and Bio-computing Program, Ontario Institute for Cancer Research, 661 University Avenue, Suite 510, Toronto, ON, M5G 0A3, Canada.|Department of Pharmacology & Toxicology, University of Toronto, Toronto, Canada.
authors.forename: Ren X
authors.initials: RX
authors.lastname: Sun
authors.affiliation: Informatics and Bio-computing Program, Ontario Institute for Cancer Research, 661 University Avenue, Suite 510, Toronto, ON, M5G 0A3, Canada.
authors.forename: John D
authors.initials: JD
authors.lastname: Watson
authors.affiliation: Informatics and Bio-computing Program, Ontario Institute for Cancer Research, 661 University Avenue, Suite 510, Toronto, ON, M5G 0A3, Canada.
authors.forename: Cindy Q
authors.initials: CQ
authors.lastname: Yao
authors.affiliation: Informatics and Bio-computing Program, Ontario Institute for Cancer Research, 661 University Avenue, Suite 510, Toronto, ON, M5G 0A3, Canada.
authors.forename: Jamie
authors.initials: J
authors.lastname: Lee
authors.affiliation: Informatics and Bio-computing Program, Ontario Institute for Cancer Research, 661 University Avenue, Suite 510, Toronto, ON, M5G 0A3, Canada.
authors.forename: Christine
authors.initials: C
authors.lastname: P'ng
authors.affiliation: Informatics and Bio-computing Program, Ontario Institute for Cancer Research, 661 University Avenue, Suite 510, Toronto, ON, M5G 0A3, Canada.
authors.forename: Renee
authors.initials: R
authors.lastname: Pang
authors.affiliation: Informatics and Bio-computing Program, Ontario Institute for Cancer Research, 661 University Avenue, Suite 510, Toronto, ON, M5G 0A3, Canada.
authors.forename: Alexander H
authors.initials: AH
authors.lastname: Wu
authors.affiliation: Informatics and Bio-computing Program, Ontario Institute for Cancer Research, 661 University Avenue, Suite 510, Toronto, ON, M5G 0A3, Canada.
authors.forename: Lauren C
authors.initials: LC
authors.lastname: Chong
authors.affiliation: Informatics and Bio-computing Program, Ontario Institute for Cancer Research, 661 University Avenue, Suite 510, Toronto, ON, M5G 0A3, Canada.
authors.forename: Ashley B
authors.initials: AB
authors.lastname: Smith
authors.affiliation: Informatics and Bio-computing Program, Ontario Institute for Cancer Research, 661 University Avenue, Suite 510, Toronto, ON, M5G 0A3, Canada.
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Harding
authors.affiliation: Department of Pharmacology & Toxicology, University of Toronto, Toronto, Canada.
authors.forename: Ivy D
authors.initials: ID
authors.lastname: Moffat
authors.affiliation: Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland.
authors.forename: Jere
authors.initials: J
authors.lastname: Lindén
authors.affiliation: Department of Biology of Physical Activity, University of Jyväskylä, Jyväskylä, Finland.|Department of Environmental Health, National Institute for Health and Welfare, Kuopio, Finland.
authors.forename: Sanna
authors.initials: S
authors.lastname: Lensu
authors.affiliation: Department of Pharmacology & Toxicology, University of Toronto, Toronto, Canada.
authors.forename: Allan B
authors.initials: AB
authors.lastname: Okey
authors.affiliation: Laboratory of Toxicology, National Institute for Health and Welfare, Kuopio, Finland.|Department of Food Hygiene and Environmental Health, University of Helsinki, Helsinki, Finland.
authors.forename: Raimo
authors.initials: R
authors.lastname: Pohjanvirta
authors.affiliation: Informatics and Bio-computing Program, Ontario Institute for Cancer Research, 661 University Avenue, Suite 510, Toronto, ON, M5G 0A3, Canada. Paul.Boutros@oicr.on.ca.|Department of Pharmacology & Toxicology, University of Toronto, Toronto, Canada. Paul.Boutros@oicr.on.ca.|Department of Medical Biophysics, University of Toronto, Toronto, Canada. Paul.Boutros@oicr.on.ca.
authors.forename: Paul C
authors.initials: PC
authors.lastname: Boutros
mesh_terms: D000818:Animals; D002460:Cell Line; D019295:Computational Biology / Q000379:methods; D004785:Environmental Pollutants / Q000494:pharmacology*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008297:Male; D051379:Mice; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D051381:Rats; D012984:Software; D059467:Transcriptome; D064878:Web Browser
chemical_list: D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins
keywords: AHR; Microarray datasets; R; TCDD