Use of SeqAPASS to extrapolate honeybee data to non-Apis bees
An AOP is a model that identifies the sequence of molecular and cellular events required to produce a toxic effect when an organism is exposed to a substance. As most AOPs are defined using a single or small number of species, they have a narrow taxonomic domain of applicability (tDOA). Defining the tDOA of an AOP is critical for use in regulatory decision-making for ecotoxicity, particularly when considering protection of untested species. Structural and functional conservation are two elements that can be considered when defining the tDOA. Publicly accessible bioinformatics approaches, such as the SeqAPASS tool, take advantage of existing and growing databases of protein sequence and structural information to provide lines of evidence toward structural conservation of key events and key event relationships of an AOP. It is anticipated that SeqAPASS results could readily be combined with data derived from empirical toxicity studies to provide evidence of both structural and functional conservation to define the tDOA for AOPs and elements of AOPs. Such data could be incorporated into resources such as the AOP-Wiki as lines of evidence toward biological plausibility for the tDOA. EPA scientists developed a case study describing the process of using bioinformatics to define the tDOA of an AOP using an AOP linking the activation of the nicotinic acetylcholine receptor to colony death/failure in the honeybee (Apis mellifera). Although the AOP was developed to gain a particular biological understanding relative to honeybee health, applicability to other Apis bees, as well as non-Apis bees, has yet to be defined. The EPA study demonstrates how bioinformatics can be utilized to rapidly take advantage of existing protein sequence and structural knowledge to enhance and inform the tDOA and elements of AOPs, focusing on providing evidence of structural conservation across species.