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BMDExpress 2: Enhanced transcriptomic dose-response analysis workflow
Citation:
Philips, J., D. Svoboda, A. Tandon, S. Patel, A. Sedykh, D. Mav, B. Kuo, C. Yauk, L. Yang, R. Thomas, Jeff Gift, Allen Davis, L. Olysyzk, F. Parham, T. Saddler, R. Shah, S. Auerbach, B. Merrick, AND R. Paules. BMDExpress 2: Enhanced transcriptomic dose-response analysis workflow. BIOINFORMATICS. Oxford University Press, Cary, NC, 35(10):1780-1782, (2019). https://doi.org/10.1093/bioinformatics/bty878
Impact/Purpose:
Agency Driver: The US EPA has to prioritize chemicals for screening under the Frank R. Lautenberg Chemical Safety for the 21st Century Act. One approach for prioritization of large numbers of chemicals is using high-throughput gene expression assays. These high throughput transcriptomic assays cover a broad biological space and provide mechanistic insights for chemical toxicity. Science Challenge: Transcriptomic dose-response modeling seeks to establish a relationship between doses of test substances and the corresponding changes in gene expression at both a gene and gene set level. The potency estimates that come from these studies can provide the doses (benchmark doses; BMD) at which these changes occur (Moffat, et al., 2015). Work has shown that BMDs identified from in vivo transcriptomic dose-response studies provide an estimate of a test article’s toxicological potency (Thomas, et al., 2013). There is significant interest in the use of genomic dose-response studies to support screening level risk assessments for environmental agents. Research Approach: BMDExpress is a software package that facilitates transcriptomic dose-response analysis (Yang, et al., 2007). It employs validated continuous parametric models from the EPA BMDS software (https://www.epa.gov/bmds) to compute curve fits for each gene expression feature, and then estimates BMDs. Results: In this work, we re-engineered and improved BMDExpress. For example, we have updated the analytical model versions, added exponential models, provided extensive data visualizations similar to those implemented in BMDExpress Viewer (Kuo, et al., 2016), incorporated on-the-fly data filtering, updated gene set annotations, added gene expression platforms, and increased the number of operating systems that are supported. Anticipated Impact/Expected Use: BMDExpress 2 offers a structured workflow for analyzing transcriptomic dose-response data with improved software performance, re-engineered code base, expanded bioinformatics methods, increased support for varied transcriptomic platforms, and updated pathway annotations. The updated version of the software (version 2) is already in use in academia, government, non-profit research institutions, and private industry for performing BMD analysis using toxicogenomic data, and it is the designated analysis platform for the NTP in its approach to transcriptomic dose-response modeling (National Toxicology Program, 2017).
Description:
Summary: A new version (version 2) of the genomic dose-response analysis software, BMDExpress, has been created. The software addresses the increasing use of transcriptomic dose-response data in toxicology, drug design, risk assessment, and translational research. In this new version, we have implemented additional statistical filtering options (e.g., Williams’ trend test), curve fitting models, Linux and Macintosh compatibility, and support for additional transcriptomic platforms with up-to-date gene annotations. Furthermore, we have implemented extensive data visualizations, on-the-fly data filtering, and a batch-wise analysis workflow. We have also significantly re-engineered the code base to reflect contemporary software engineering practices and streamline future development. Motivation: The first version of BMDExpress was developed in 2007 to meet an unmet demand for easy-to-use transcriptomic dose response analysis software. Since its original release, however, transcriptomic platforms, technologies, pathway annotations, and quantitative methods for data analysis have undergone a large change necessitating a significant re-development of BMDExpress. To that end, as of 2016, the National Toxicology Program assumed stewardship of BMDExpress. The result is a modernized and updated BMDExpress 2 that addresses the needs of the growing toxicogenomics user community. Availability: BMDExpress 2 is available at: https://github.com/auerbachs/BMDExpress-2/releases
