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SeqAPASS: Sequence alignment to predict across-species susceptibility
LaLone, C., D. Villeneuve, H. Helgen, AND G. Ankley. SeqAPASS: Sequence alignment to predict across-species susceptibility. Presented at SETAC Europe, Basel, SWITZERLAND, May 11 - 15, 2014.
Efforts to shift the toxicity testing paradigm from whole organism studies to those focused on the initiation of toxicity and relevant pathways have led to increased utilization of in vitro and in silico methods. Hence the emergence of high through-put screening (HTS) programs, such as U.S. EPA ToxCast, and application of the adverse outcome pathway (AOP) framework for identifying and defining biological key events triggered upon perturbation of molecular initiating events and leading to adverse outcomes occuring at a level of organization relevant for risk assessment . With these recent initiatives to harness the power of “the pathway” in describing and evaluating toxicity comes the need to extrapolate data beyond the model species. Sequence alignment to predict across-species susceptibilty (SeqAPASS) is a web-based tool that allows the user to begin to understand how broadly HTS data or AOP constructs may plausibly be extrapolated across species, while describing the relative intrinsic susceptibiltiy of different taxa to chemicals with known modes of action (e.g., pharmaceuticals and pesticides). The tool rapidly and strategically assesses available molecular target information to describe protein sequence similarity at the primary amino acid sequence, conserved domain, and individual amino acid residue levels. This in silico approach to species extrapolation was designed to automate and streamline the relatively complex and time-consuming process of comparing protein sequences in a consistent, logical, and criteria driven manner intended for predicting across species susceptibility to a chemical perturbation. To define the domain of applicability and enhance the utility of the SeqAPASS tool, multiple case studies have been explored, including the derivation of predictions for across species susceptibilty to chemicals that target the human estrogen receptor, bovine androgen receptor, mosquito voltage-gated sodium channel, fungus cytochrome P450 51, and honey bee nicotinic acetylcholine receptor. These examples highlight the utility of the SeqAPASS tool for researchers and regulators alike.
Record Details:Record Type: DOCUMENT (PRESENTATION/SLIDE)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LAB
MID-CONTINENT ECOLOGY DIVISION