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DEMO: Sequence Alignment to Predict Across Species Susceptibility
Citation:
LaLone, C. DEMO: Sequence Alignment to Predict Across Species Susceptibility. SETAC Focused Topic, Durham, NC, April 16 - 18, 2018.
Impact/Purpose:
The US EPA’s Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS; https://seqapass.epa.gov/seqapass/) was developed to evaluate similarity of species at the molecular level. SeqAPASS takes a rather complex, time-consuming, technically intensive method, and simplifies it, making it useful for non-experts in the field of protein biology. This tool puts a powerful methodology in the hands of anyone interested in gathering a greater understanding about the potential for a chemical to cause adverse effects across species. Data output provides a prediction of likely susceptible or not likely susceptible for hundreds to thousands of species. This evaluation is entirely computer driven, taking advantage of available empirical data. Therefore, a great deal of information can be gathered without the need for toxicity testing with animals.
Description:
The US Environmental Protection Agency Sequence Alignment to Predict Across Species Susceptibility tool (SeqAPASS; https://seqapass.epa.gov/seqapass/) was developed to comparatively evaluate protein sequence and structural similarity across species as a means to extrapolate toxicity data/knowledge. SeqAPASS output provides a prediction of chemical susceptibility based on principles of evolutionary biology in understanding species relatedness at the molecular level. The tool takes advantage of the growing publically available protein information housed in the National Center for Biotechnology Information protein database which currently contains 102,133,844 proteins representing 75,218 organisms. Access to this expanding data source through SeqAPASS accommodates extrapolation for a variety of research and regulatory challenges, allowing for extrapolation from any species to all other species for which protein sequence data exists. Additionally, flexibility in the analysis, moving from primary amino acid sequence evaluations to structural consideration, allows the user to capitalize on any existing information pertaining to chemical-protein interactions in known sensitive species. Therefore, SeqAPASS evaluations can evolve over time to expand species coverage with additional sequence data and additional levels of analysis with more in depth knowledge of chemical sensitivity and protein structure. Overall, SeqAPASS provides robust susceptibility predictions across hundreds to thousands of species to address challenges of species extrapolation that cannot feasibly be addressed through traditional empirical testing. Data derived from the SeqAPASS tool have been applied in the context of extrapolating chemical toxicity data (primarily pesticides and drugs), high-throughput screening results, and adverse outcome pathway knowledge. The data has also been used for chemical prioritization and hypothesis generation. Recent enhancements to the tool include interactive data visualization options for ease of data interpretation. The primary goal in developing SeqAPASS was to take a rather complex evaluation and simplify it, making it useful and easy to use for scientists and decision-makers that may have never considered the evaluation of protein sequence and structural information as a component of their mainstream toolbox for use in species-extrapolation. The contents of this abstract neither constitute nor reflect official US EPA policy.