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Extrapolating toxicity data across species using U.S. EPA SeqAPASS tool
Citation:
LaLone, C. Extrapolating toxicity data across species using U.S. EPA SeqAPASS tool. OECD Endocrine Disruptor Testing and Assessment (EDTA), Duluth, MN, October 04, 2017.
Impact/Purpose:
The U.S. EPA Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) tool was used to assess conservation of the 460 protein targets represented in the ToxCast assay suite. The SeqAPASS query sequence was selected based on the model organism used in the ToxCast assay (e.g., human, cattle, chimpanzee, guinea pig, rabbit, rat, mouse, pig, or sheep). Similarity of primary amino acid sequences and sequences from appropriate functional domains were compared across species to understand conservation of each assay target across taxa and probe questions of species extrapolation. To demonstrate the applicability of the SeqAPASS data for extrapolation of ToxCast targets, we developed case studies focused on the extrapolation of targets being evaluated as a component of the Endocrine Disruptor Screening Program. These case studies demonstrate the utility of SeqAPASS for informing the extrapolation of ToxCast data and identification of model organisms likely to be suitable for follow-up or complementary in vivo toxicity tests.
Description:
In vitro high-throughput screening (HTS) and in silico technologies have emerged as 21st century tools for chemical hazard identification. In 2007 the U.S. Environmental Protection Agency (EPA) launched the ToxCast Program, which has screened thousands of chemicals in hundreds of (primarily) mammalian-based HTS assays for biological activity suggestive of potential toxic effects. Data generated through this effort are being used to prioritize toxicity testing on chemicals most likely to lead to adverse health effects. To realize the full potential of the ToxCast data for predicting adverse effects to both humans and wildlife, it is necessary to understand how broadly these data may plausibly be extrapolated across species. Therefore, the U.S. EPA Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) tool was used to assess conservation of the 460 protein targets represented in the ToxCast assay suite. The SeqAPASS query sequence was selected based on the model organism used in the ToxCast assay (e.g., human, cattle, chimpanzee, guinea pig, rabbit, rat, mouse, pig, or sheep). Similarity of primary amino acid sequences and sequences from appropriate functional domains were compared across species to understand conservation of each assay target across taxa and probe questions of species extrapolation. To demonstrate the applicability of the SeqAPASS data for extrapolation of ToxCast targets, we developed case studies focused on the extrapolation of targets being evaluated as a component of the Endocrine Disruptor Screening Program. These case studies demonstrate the utility of SeqAPASS for informing the extrapolation of ToxCast data and identification of model organisms likely to be suitable for follow-up or complementary in vivo toxicity tests.