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Incorporating new features for rapid interpretation of results from the Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) Tool
Citation:
Blatz, D., S. Vliet, S. Mayasich, C. Simmons, T. Transue, AND C. LaLone. Incorporating new features for rapid interpretation of results from the Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) Tool. SETAC North America, Fort Worth, TX, November 15 - 19, 2020. https://doi.org/10.23645/epacomptox.13129847
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 pesticides and demonstrate new features of the tool.
Description:
The US Environmental Protection Agency (EPA) is slowly moving away from animal testing over the next 15 years. Now, more than ever, computational tools that evaluate chemical safety and species susceptibility are advancing to the forefront of research to aid decision makers and risk accessors. The Sequence Alignment to Predict Across Species Susceptibility tool (SeqAPASS; https://seqapass.epa.gov/seqapass/) compares proteins from numerous species to understand conservation of chemical targets using three levels of sequence comparison to a known sensitive species. The first comparison evaluates primary amino acid sequences (Level 1), the second aligns conserved domains (Level 2), and the third compares critical amino acid residue similarity (Level 3), where each Level incorporates additional lines of evidence to predict chemical susceptibility rapidly to hundreds of species at a time. Results from such approaches can take hours to analyze in multiple files and excel spreadsheets. Two major updates have been integrated in the SeqAPASS pipeline which include a heat map visualization of individual amino acid comparisons (Level 3) and a Decision Summary report that allows for a combination of susceptibility predictions across the Levels evaluation. The new heat map visualization will allow for a quick and easy discernment of amino acid similarities and differences across taxonomic groups and species. This feature will allow users to make rapid predictions of susceptibility based on known critical amino acids and develop hypotheses as to which amino acids may cause a difference in susceptibility prediction for a particular species. The Decision Summary report is a user customizable report that can provide a complete and organized way to see all information regarding an evaluation with a specific protein target. The customizable options cater to the different levels of the SeqAPASS analyses and predictions that can be produced as well as providing options to integrate the data visualizations in a pdf printable form. A case example will demonstrate the utility of the new SeqAPASS features focused on susceptibility pesticides to key pollinator species.
URLs/Downloads:
DOI: Incorporating new features for rapid interpretation of results from the Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) Tool