Advancing Species Extrapolation: EPA’s “Sequence Alignment to Predict Across Species Susceptibility”

By Carlie A. LaLone, Ph.D.

Graphic illustration of molecule with shapes of animals in front. I have been working with a team of EPA colleagues to create an on-line tool, Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS), that will help both researchers and regulators readily use available protein sequence and structural knowledge to extrapolate chemical toxicity information across species. When complete, this innovative research tool will help predict potential chemical susceptibility to wildlife, including plants and animals.

Through the years, scientists have come to understand that the sensitivity of a species to a chemical is determined by a number of factors including chemical exposure, absorption, distribution, metabolism, elimination, and the organism’s life-history. Additionally, an important consideration for species susceptibility is the presence or absence of proteins that interact with chemicals. Those that interact can be referred to as “protein targets.” Researchers take advantage of such protein targets to develop or improve drugs and/or pesticides, however it is known that chemicals in the environment can interact with these protein targets in other non-target species leading to unintended adverse effects.

Chemicals such as pharmaceuticals and pesticides have relatively well-defined protein targets and a majority of these proteins are curated in the National Center for Biotechnology Information (NCBI) protein database maintained by the National Library of Medicine at the National Institutes of Health. The database contains information on millions of proteins from thousands of different species. Using this massive and continually expanding database, SeqAPASS helps identify whether a protein target is available for a chemical to act upon in a particular species, which could therefore potentially disrupt important biological processes. This method can be used, for example, to explore whether a pesticide developed to control a pest species would be predicted to affect other, non-target species such as pollinators or protected (threatened or endangered) species.

Overall, SeqAPASS provides us with a fast, efficient screening tool. Using it, we can begin to extrapolate toxicity information from a few model organisms (like mice, rats, zebrafish, etc.) to thousands of other non-target species to evaluate potential chemical susceptibility.

SeqAPASS provides an example of how EPA Chemical Safety for Sustainability researchers are leading the effort to usher in a new generation of toxicology practices that aspire to reduce the number of animals used, decrease costs, and increase the efficiency of chemical toxicity testing. The 21st century chemical toxicity testing strategy incorporates these ideals and has given rise to adverse outcome pathway (AOP) development and rapid, high-throughput chemical screening programs such as EPA’s ToxCast program.

We plan to make SeqAPASS publically available later this year. I am very passionate about the work we are doing and hope that future external engagement will enhance the SeqAPASS tool capabilities and its applications. As this project continues to evolve to incorporate the latest bioinformatic technologies for protein comparisons across species, we hope that SeqAPASS can be used to inform risk assessments, particularly in instances where toxicity data is lacking.

This research has been published in Aquatic Toxicology, Philosophical Transactions of the Royal Society B and Environmental Toxicology and Chemistry. Another paper has been drafted to coincide with public release of SeqAPASS via the internet.

About the Author: Carlie LaLone is a Postdoctoral Associate for the University of Minnesota Water Resources Center in Cooperative Training Partnership with EPA’s Office of Research and Development. She is the project lead for the development of the Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) tool.

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