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SeqAPASS: Predicting chemical susceptibility to threatened/endangered species
Citation:
LaLone, C. SeqAPASS: Predicting chemical susceptibility to threatened/endangered species. SETAC North America, Minneapolis, MN, November 12 - 16, 2017.
Impact/Purpose:
Toxicity data capturing the direct effect of chemicals on endangered species is relatively unattainable. In practice, surrogate model organisms are used to study and describe the potential for adverse chemical effects to threatened and endangered species. With the growing number of chemicals entering the environment, it is not practical to gather toxicity data across numerous model organisms and therefore such information may only exist for a single species (or a handful of species at the most). With limited toxicity data available, the U.S. Environmental Protection Agency’s Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) computer tool, which takes advantage of existing protein sequence data to predict cross-species chemical susceptibility, can be used to better understand the potential for chemicals to act on threatened and endangered species. Because sequence information can be gathered via non-destructive means, more and more information on threatened and endangered species is becoming available. SeqAPASS compares protein sequence data between known sensitive species and all other species to provide a line of evidence that another species may be susceptible to a given chemical based on presence or absence of a known chemical protein target. The SeqAPASS tool was used to provide a line of evidence that threatened or endangered butterfly species are likely to contain the protein, the ecdysone receptor, which is the target of certain pesticides that lead to premature molting in pest insects. This evidence was based on sequence and structural comparisons between targeted insects and all sequences available for butterfly species indicating that the proteins are highly similar. Therefore, this information can be used as a line of evidence to inform the Endangered Species Act.
Description:
Conservation of a molecular target across species can be used as a line-of-evidence to predict the likelihood of chemical susceptibility. The web-based Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS; https://seqapass.epa.gov/seqapass/) application was developed to simplify, streamline, and quantitatively assess protein sequence/structural similarity across taxonomic groups as a means to predict relative intrinsic susceptibility. The intent of the tool is to allow for evaluation of any potential protein target while remaining amenable to variable degrees of protein characterization, in the context of available information about the chemical/protein interaction and the molecular target itself. To accommodate this flexibility in the analysis, three levels of evaluation were developed. The first level of the SeqAPASS analysis compares primary amino acid sequences to a query sequence, calculating a metric for sequence similarity (including detection of orthologs); the second level evaluates sequence similarity within selected functional domains (e.g., ligand-binding domain); and the third level of analysis compares individual amino acid residue positions of importance for protein conformation and/or interaction with the chemical upon binding. Each level of the SeqAPASS analysis provides additional evidence to apply toward rapid, screening-level assessments of probable cross species susceptibility. Such analysis can provide valuable insights as to the potential chemical susceptibility of such species lacking empirical toxicity test data such as the case with threatened and endangered species. To better understand the potential for chemicals to act on threatened and endangered species, a case study was developed demonstrating how SeqAPASS can be used to evaluate the potential susceptibility of endangered butterfly to molt-accelerating compounds.