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Enhancing the utility of the Sequence Alignment to Predict Across Species Susceptibility tool
Citation:
Finnegan, C., J. Doering, AND C. LaLone. Enhancing the utility of the Sequence Alignment to Predict Across Species Susceptibility tool. SETAC Europe, Helsinki, N/A, FINLAND, May 26 - 30, 2019.
Impact/Purpose:
The US EPA’s Sequence Alignment to Predict Across Species Susceptibility tool (SeqAPASS; https://seqapass.epa.gov/seqapass/) is a web-based application that allows the user to begin to understand how broadly toxicity information may plausibly be extrapolated across species. This is critical, because for a majority of chemicals there is very little, if any, laboratory studies evaluating chemical safety for multiple species. Typically, if toxicity data exists it is available for only a limited number of model organisms (one or a handful of species). The SeqAPASS tool takes available toxicity information for a species and using protein sequence and structural comparisons, makes predictions for chemical susceptibility across hundreds of non-tested species. The SeqAPASS tool was initially released to the public in 2016. Since that time, a significant effort has gone toward training (e.g., Introduction to SeqAPASS: Hands-on Training) and outreach with the tool to capture new users. These outreach efforts have occurred both internally at EPA and externally (e.g., demonstrations/short course at professional meetings). From these efforts, SeqAPASS developers have utilized user input to identify critical areas for enhanced functionality and user-friendly features, including the need for help menus and greater integration of existing tools. Such enhancements are anticipated to grow the user base and improve consistency in susceptibility predictions across species and across users. Additionally, as a means to grow the user base it is essential that case studies continue to be developed demonstrating the application of the tool for challenges important to the Agency, such as in evaluating cross species susceptibility to pesticide chemicals where limited toxicity data are available. Therefore, for this presentation a case study was developed looking at cross-species susceptibility to diamide pesticides.
Description:
The number of new chemicals introduced to commerce each year exceeds the practical ability to experimentally determine the consequences of those chemicals on all species that may be exposed. To address this challenge new approach methods are increasingly becoming important as supplementary evidence for chemical safety evaluations. A new approach method for predicting cross-species chemical susceptibility is the Sequence Alignment to Predict Across Species Susceptibility tool (SeqAPASS v3; https://seqapass.epa.gov/seqapass/). SeqAPASS is a web-based tool that allows the user to begin to understand how broadly toxicity information may plausibly be extrapolated across species, while describing the relative intrinsic susceptibility of different taxa to chemicals with known modes of action (e.g., pesticides, pharmaceuticals, other specifically acting chemicals). The tool rapidly and strategically assesses available molecular target information to describe protein sequence and structural similarity at the primary amino acid sequence, conserved domain(s), and individual amino acid residue levels. Development of the SeqAPASS tool is an iterative process making improvements by gathering information from users through training and outreach to identify new functionality and user-friendly features for implementation. Such features are anticipated to grow the user base and improve susceptible predictions. Recently the SeqAPASS development team has begun to integrate help menus and tools tips, as well as features for interoperability with other tools (e.g., ECOTOX Knowledgebase; https://cfpub.epa.gov/ecotox/) for the next release of SeqAPASS v4 anticipated for 2019. Additionally, it is critical to continue to continue to demonstrate the utility of the SeqAPASS tool in predicting cross-species chemical susceptibility. Therefore, a case study was developed considering cross-species susceptibility to diamide insecticides.