Editors Highlight: Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS): A Web-Based Tool for Addressing the Challenges of Cross-Species Extrapolation of Chemical Toxicity

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, 3 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 (eg, 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 analyses can support prioritization of chemicals for further e...

Source: Toxicological Sciences - September 25, 2016 Category: Toxicology Authors: LaLone, C. A., Villeneuve, D. L., Lyons, D., Helgen, H. W., Robinson, S. L., Swintek, J. A., Saari, T. W., Ankley, G. T. Tags: Web-Based Tool for Cross-Species Extrapolation of Chemical Toxicity Source Type: research