BMDExpress 2: enhanced transcriptomic dose-response analysis workflow

Abstract

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, onthe-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. The first version of BMDExpress was developed in 2007 to meet an unmet demand for easy-touse 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 redevelopment 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.

Transcriptomics in Toxicogenomics, Part I: Experimental Design, Technologies, Publicly Available Data, and Regulatory Aspects

“…Traditionally, these methods require time-and resource-consuming methodologies of biological parameters such as tumor incidence, cell proliferation, or body weight changes. TGx, instead, provides faster strategies for determining BMD levels, with less screening and animal experiments [32]. Moreover, the goal of BMD is to build estimates about safe daily exposure levels, and for this, TGx approach can provide faster predictions allowing complex modeling of gene expression changes in thousands of features simultaneously.…”

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].…”

High-throughput transcriptomics and benchmark concentration modeling for potency ranking of per- and polyfluoroalkyl substances (PFAS) in exposed human liver cell spheroids

“…Concentration response curves from high-throughput transcriptomic data were produced using the transcriptomic workflow described by Philips et al for BMDExpress v2.3 (Phillips et al, 2019). Each gene BMC represents the concentration where transcript levels deviated from the baseline of background concentration by the predesignated benchmark response (1 standard deviation).…”