About this Research Topic
With the vast and increasing accumulation of biological data, combined with rapidly evolving technological advances in both life science and computer science, there comes an opportunity to evolve our approach to the practical applications of biological research to fully take advantage of this progress. To increase the utility of biological data, these data must be evaluated for quality, placed into context with other relevant information and be publicly available (preferably in a machine-readable format). One such framework for transforming data in this way is the Adverse Outcome Pathway (AOP) framework. Originally developed to support the use of New Approach Methodologies (NAMs) in chemical safety evaluation, as well as to facilitate regulatory update of NAMs, the AOP framework allows the assimilation of all types of information at different levels of biological organization, from molecular to population, that pertain to a particular biological process. This allows the explicit description (and thereby understanding) of the sequence of biological events (or “key events”) that occur as a result of a perturbation of this pathway, either by chemical exposure, disease, or other “stressor.” A comprehensive description of a chemical’s potential activity or disease likely involves multiple AOPs or AOP networks.
Generally, prediction of adverse outcomes requires the assimilation of multiple streams of evidence within a decision context – or an Integrated Approach to Testing and Assessment (IATA). Within IATA, AOPs provide the transparent biological understanding that supports development and testing of biological hypotheses, weight of evidence arguments, design of testing strategies, development of NAMs, hazard identification and assessment, and/or risk assessment. As quantitative understanding of the relationships between key events improves, the AOP can support the development of prediction models.
In addition to the application of AOPs in toxicology, AOPs can be similarly applied to the field of biomedicine to support the understanding of disease and aid in drug design. Overall, the AOP framework is essential to evolving the future utility of biological information and NAMs, in the realms of chemical safety and medical research.
This Research Topic will present a comprehensive overview of the AOP and IATA frameworks, and target the solicitation of case studies related to the use of AOPs to support IATA in chemical safety assessment or disease that highlight different applications. Each of the case authors will be tasked with providing an overview of the benefits and challenges of applying the AOP framework.
Keywords: AOP Framework, New Approach Methodologies, NAMs, in vitro methods, mechanistic-based approaches, Integrated Approaches to Testing and Assessment, IATA
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