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The US EPA Sequence Alignment to Predict Across Species Susceptibility tool for species extrapolation
Citation:
Lalone, C., J. Doering, AND C. Finnegan. The US EPA Sequence Alignment to Predict Across Species Susceptibility tool for species extrapolation. SETAC North America, Toronto, ON, CANADA, November 03 - 07, 2019.
Impact/Purpose:
Understanding species similarities and differences can aid in understanding whether or not they may be sensitive to a chemical in the environment. There are a number of ways in which such similarity can be assessed, for example through visual inspection or based on similar traits. However, another means to assess species similarity is by comparing them at the molecular level, specifically by examining their protein similarity. Proteins are involved in chemical interactions that can set off a series of biological events that lead to an adverse effect. Therefore, if there is knowledge that a species is sensitive to a given chemical through interaction with a specific protein, we can look at other species to understand whether they also express that protein and if so, we can predict whether they may be susceptible to the chemical as well. This is the premise behind the web-based tool created by the US EPA, the Sequence Alignment to Predict Across Species Susceptibility tool (SeqAPASS). The tool allows users to quickly evaluate similarity between proteins across species to make predictions of chemical susceptibility. This presentation will highlight the methods and features that make up the SeqAPASS tool.
Description:
For any given chemical limited toxicity test data exists and typically, if available, the data only represents that generated from a few model species. Therefore, the necessity to extrapolate existing toxicity knowledge collected from one species to others is a prominent challenge in chemical safety evaluations. This challenge is heightened in considering chemical impacts to threatened and endangered species where toxicity testing is impractical. Overall, it is critical to advance innovative methods and technologies for cross species extrapolation to inform chemical safety decisions. One such technology is the US Environmental Protection Agency Sequence Alignment to Predict Across Species Susceptibility tool (SeqAPASS; https://seqapass.epa.gov/seqapass), that capitalizes on existing and continuously expanding protein sequence and structural information to evaluate similarities and differences in chemical molecular targets across species. Based on the similarity of a known sensitive species to other species, a prediction of chemical susceptibility can be elucidated across hundreds to thousands of species. The tool relies on prior knowledge of a chemical protein target and a sensitive species and uses that information as a starting point to compare to primary amino acid sequences, functional domains, and critical amino acids across species. SeqAPASS is flexible in that it allows the user to utilize all available information about the chemical protein interaction from the linear protein sequence to understanding of the tertiary structure of the protein. The results from the SeqAPASS tool can be downloaded as tables (.csv or .xlsx files) and visualized through an interactive box-plot graphic, that can also be downloaded. The newest release of SeqAPASS v4.0 will provide help menus and query guidance for the user, as well as rapidly interpretable data summary tables, with continuously improving user friendly features for streamlined navigation of the interface. Methods developed in the SeqAPASS tool aim to capture the state-of-the-science in protein comparison techniques and will continue to evolve as bioinformatic approaches improve and become more automated, particularly surrounding protein structural comparisons across species.