Citation:

LaLone, C. SeqAPASS v3.0 for Extrapolation of Toxicity Knowledge Across Species. NTP Interagency Center for theEvaluation of Alternative Toxicological Methods, Duluth, MN, May 29, 2018.

Impact/Purpose:

The SeqAPASS v3.0 tool allows users to compare protein similarity across species. This is important because chemicals act on protein targets. Therefore, by understanding how similar proteins are across species, the SeqAPASS tool can produce predictions of chemical susceptibility across hundreds of species rapidly. This presentation will be an overview of the challenges in extrapolating toxicity data/knowledge across species and a description of the functionality of the tool itself using case study examples to highlight features.

Description:

The U.S. Environmental Protection Agency Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS; https://seqapass.epa.gov/seqapass/) tool was initially released to the public in 2016, providing a novel means to begin to address challenges in extrapolating toxicity data and knowledge across species. The SeqAPASS tool was designed to take advantage of continuously expanding protein sequence data, readily available for tens of thousands of species, for predictions of chemical susceptibility. The assumption underlying the SeqAPASS tool is that the greater the similarity between the protein target in a sensitive or model organism to other species, the more likely the protein in the other species functions similarly, either binding to a chemical or performing a similar role in a pathway. This knowledge of conservation across species from SeqAPASS provides a rapid mechanism for understanding how well model organisms serve as surrogates for other untested species and provides a line of evidence for extrapolation of toxicity or pathway data to other species based on chemical molecular target conservation. Depending on how well a protein target has been characterized and the degree of knowledge about a chemical-protein interaction, three levels of SeqAPASS evaluation can be performed. Level 1 evaluates similarity at the primary amino acid sequence, Level 2 at the functional domain, and Level 3 at the individual amino acid residue adding taxonomic resolution to predictions when advancing through each level of the analysis. Recently, version 3.0 of the SeqAPASS tool was released with integration of interactive data visualization capabilities and significant advances in automated Level 3 data interpretation for predictions of chemical susceptibility. These enhancements to SeqAPASS v3.0 focused on implementing suggestions for improved functionality received from stakeholder engagement with the overall intent on making the tool more user friendly. This presentation will focus on descriptions of the new features using case studies to demonstrate application of the tool.

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