BMDExpress: a software tool for the benchmark dose analyses of genomic data

Abstract

Background: Dose-dependent processes are common within biological systems and include phenotypic changes following exposures to both endogenous and xenobiotic molecules. The use of microarray technology to explore the molecular signals that underlie these dose-dependent processes has become increasingly common; however, the number of software tools for quantitatively analyzing and interpreting dose-response microarray data has been limited.

Results: We have developed BMDExpress, a Java application that combines traditional benchmark dose methods with gene ontology classification in the analysis of dose-response data from microarray experiments. The software application is designed to perform a stepwise analysis beginning with a one-way analysis of variance to identify the subset of genes that demonstrate significant dose-response behavior. The second step of the analysis involves fitting the gene expression data to a selection of standard statistical models (linear, 2 degrees polynomial, 3 degrees polynomial, and power models) and selecting the model that best describes the data with the least amount of complexity. The model is then used to estimate the benchmark dose at which the expression of the gene significantly deviates from that observed in control animals. Finally, the software application summarizes the statistical modeling results by matching each gene to its corresponding gene ontology categories and calculating summary values that characterize the dose-dependent behavior for each biological process and molecular function. As a result, the summary values represent the dose levels at which genes in the corresponding cellular process show transcriptional changes.

Conclusion: The application of microarray technology together with the BMDExpress software tool represents a useful combination in characterizing dose-dependent transcriptional changes in biological systems. The software allows users to efficiently analyze large dose-response microarray studies and identify reference doses at which particular cellular processes are altered. The software is freely available at http://sourceforge.net/projects/bmdexpress/ and is distributed under the MIT Public License.

Figure 1

Screen shots of BMDExpress software application. The software uses standard drop-down windows for user interaction and the left-hand side of the main window contains a tree structure that outlines progress through the analysis process. (A) Interface for data import. The data is previewed in table format and if the input data has column headers, the user is provided the option to remove headers within the software interface. (B) Interface for pre-filtering data using a one-way ANOVA. The user is allowed to input an adjusted p-cutoff and select whether to filter out the various control genes (e.g., BioB, BioC, etc.) present on an Affymetrix array. (C) Interface for benchmark dose analysis. The user is allowed to select the type of statistical models and parameters used in the analysis and provided options on the process of selecting the best model. (D) Interface for gene ontology analysis. The BMD values from the previous step in the analysis process are used as input for the gene ontology analysis. The organism is automatically detected by the software based on the probe set identifiers. The user is allowed to select the class of gene ontology categories for the analysis with either biological process, molecular function, cell component, or universal (all three) as options.