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.

Transcriptional benchmark dose modeling: Exploring how advances in chemical risk assessment may be applied to the radiation field

“…In Defined Category Analysis, the probes were converted to NCBI gene identifiers. Export files from BMDExpress were uploaded to BMDExpress Data Viewer [Kuo et al, ] for visualization of gene BMD, pathway BMD mean/median and model distributions. Dataset Exploratory Tools, including Functional Enrichment Analysis and Multiple Dataset Comparison were used for data analyses.…”

“…To meet this end, datasets were obtained from the Gene Expression Omnibus (GEO) and analyzed alongside datasets generated in‐house using BMDExpress (version 1.41) [Yang et al, ]. BMD values were derived for individual genes and pathways and compared across cell lines, dose ranges and time‐points using BMDExpress Data Viewer (version 1.02) [Kuo et al, ]. Analysis included an assessment of the distribution of BMD values across genes/pathways with information on the best fit model for each gene.…”

Transcriptomics in Toxicogenomics, Part III: Data Modelling for Risk Assessment

“…A similar pipeline for toxicogenomics applications is implemented in the java-based US National Toxicology Program's BMDExpress 2 tool, where a dose-response model is fitted for every gene, whose expression value is the response variable for the different doses [39][40][41] (Table 1). Furthermore, an R package for the dose-response analysis of gene expression data, called ISOgene has been proposed [42,43].…”

The application of transcriptional benchmark dose modeling for deriving thresholds of effects associated with solar‐simulated ultraviolet radiation exposure

“…Global interest in the use of transcriptional profiling for risk assessment has led to the development of new high‐throughput analytical approaches to assess dose‐response [Yang et al, ; Kuo et al, ]. However, although substantial amounts of transcriptional data have been generated in the UVR field, the data have been predominantly used to support an understanding of mechanistic effects.…”