title: BMDExpress Data Viewer - a visualization tool to analyze BMDExpress datasets.
abstract: Regulatory agencies increasingly apply benchmark dose (BMD) modeling to determine points of departure for risk assessment. BMDExpress applies BMD modeling to transcriptomic datasets to identify transcriptional BMDs. However, graphing and analytical capabilities within BMDExpress are limited, and the analysis of output files is challenging. We developed a web-based application, BMDExpress Data Viewer (http://apps.sciome.com:8082/BMDX_Viewer/), for visualizing and graphing BMDExpress output files. The application consists of "Summary Visualization" and "Dataset Exploratory" tools. Through analysis of transcriptomic datasets of the toxicants furan and 4,4'-methylenebis(N,N-dimethyl)benzenamine, we demonstrate that the "Summary Visualization Tools" can be used to examine distributions of gene and pathway BMD values, and to derive a potential point of departure value based on summary statistics. By applying filters on enrichment P-values and minimum number of significant genes, the "Functional Enrichment Analysis" tool enables the user to select biological processes or pathways that are selectively perturbed by chemical exposure and identify the related BMD. The "Multiple Dataset Comparison" tool enables comparison of gene and pathway BMD values across multiple experiments (e.g., across timepoints or tissues). The "BMDL-BMD Range Plotter" tool facilitates the observation of BMD trends across biological processes or pathways. Through our case studies, we demonstrate that BMDExpress Data Viewer is a useful tool to visualize, explore and analyze BMDExpress output files. Visualizing the data in this manner enables rapid assessment of data quality, model fit, doses of peak activity, most sensitive pathway perturbations and other metrics that will be useful in applying toxicogenomics in risk assessment. © 2015 Her Majesty the Queen in Right of Canada. Journal of Applied Toxicology published by John Wiley & Sons, Ltd.
authors.affiliation: Environmental Health Science and Research Bureau, Health Canada, Ottawa, ON, Canada, K1A 0K9.
authors.forename: Byron
authors.initials: B
authors.lastname: Kuo
authors.affiliation: Environmental Health Science and Research Bureau, Health Canada, Ottawa, ON, Canada, K1A 0K9.|Department of Biology, Carleton University, 1125 Colonel By Drive, Ottawa, K1S 5B6, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Francina Webster
authors.affiliation: United States Environmental Protection Agency, Office of Research and Development, National Center for Computational Toxicology, Research Triangle Park, NC, 27711, USA.
authors.forename: Russell S
authors.initials: RS
authors.lastname: Thomas
authors.affiliation: Environmental Health Science and Research Bureau, Health Canada, Ottawa, ON, Canada, K1A 0K9.
authors.forename: Carole L
authors.initials: CL
authors.lastname: Yauk
mesh_terms: D000814:Aniline Compounds / Q000633:toxicity*; D000818:Animals; D019985:Benchmarking / Q000379:methods*; D002874:Chromosome Mapping; D016208:Databases, Factual; D004305:Dose-Response Relationship, Drug; D005663:Furans / Q000633:toxicity*; D016678:Genome; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D018570:Risk Assessment; D012984:Software; D043922:Toxicogenetics; D059467:Transcriptome
chemical_list: D000814:Aniline Compounds; D005663:Furans; C035472:N,N,N',N'-tetramethyl-4,4'-methylenedianiline; C039281:furan
keywords: 4,4′-methylenebis(N,N-dimethyl)benzenamine (MDMB); BMDExpress; benchmark dose (BMD); bioinformatics; data visualization; dose-response; furan; gene expression; genomics; human health risk assessment; microarray; transcriptomics