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Approaches and models for species extrapolation
Citation:
LaLone, C. Approaches and models for species extrapolation. EPA Board of Scientific Councilors (BOSC) Virtual Meeting, Duluth, MN, February 02 - 05, 2021. https://doi.org/10.23645/epacomptox.13619279
Impact/Purpose:
This presentation describes the research being conducted in Dr. Carlie LaLone’s Lab relative to understanding the effects of chemicals across species using computational and molecular methods to understand cross species similarities and differences that predict chemical susceptibility. Case examples are also used to demonstrate the domain of applicability for such approaches.
Description:
Cross species extrapolation is a challenge in chemical safety evaluations due to a lack of empirical data and the use of model organisms as surrogate species. To address this challenge the Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) tool has been created and continues to evolve to use bioinformatic techniques to assess species similarities and differences at the protein level. Since chemical perturbation of biological pathways commonly occurs via protein interactions, knowledge of how a chemical interacts in one chemical can be used to predict whether it is likely to interact in another species. Therefore, understanding whether a protein is conserved or not in another species adds lines of evidence that the other species could also be susceptible to the chemical. The SeqAPASS tool also compares individual amino acids to make species specific predictions of chemical susceptibility. To confirm SeqAPASS based predictions and re-iterate if necessary, our lab is using a number of different laboratory approaches including site-directed mutagenesis. In addition to SeqAPASS, we have applied approaches in systematic review to gather existing in vitro and in vivo data that can assist in defining the domain of applicability for chemical perturbation of biological pathways. Finally, to advance our predictive capabilities our lab is exploring the use of advanced molecular modeling techniques. This work is being conducted to directly align with Program Office partner needs relative to the endocrine disruptor screening program, pollinators, and understanding effects of Perfluoroalkyl Substances.
