Open AccessAOPERA: A proposed methodology and inventory of effective tools to link chemicals to adverse outcome pathways
Author(s) -
Taylor Rycroft,
Christy M. Foran,
Adam Thrash,
Jeffrey C. Cegan,
R. Zollinger,
Igor Linkov,
Edward J. Perkins,
Natàlia García-Reyero
Publication year - 2019
Publication title -
altex/alternatives to animal experimentation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.975
H-Index - 51
eISSN - 1868-8551
pISSN - 1868-596X
DOI - 10.14573/altex.1906201
Subject(s) - adverse outcome pathway , process (computing) , outcome (game theory) , computer science , process safety , process management , chemical safety , risk analysis (engineering) , biochemical engineering , knowledge management , computational biology , work in process , business , operations management , biology , engineering , mathematics , mathematical economics , operating system
New approaches, like the Adverse Outcome Pathway (AOP) framework, have been developed to describe how chemicals cause toxicity by linking in vitro assays to adverse health outcomes. However, approaches, tools and resources for development of AOPs have not been well described. Here we review information resources for AOP development and define a streamlined process for linking a chemical to an existing AOP. We propose a four step process to facilitate AOP development: link the uncharacterized chemical directly to Molecular Initiating Events, Key Events, or Adverse Outcomes; identify analogs with toxicological information for the uncharacterized chemical; link the characterized chemical (initial chemical if characterized, a characterized analog if initial chemical is not) to Molecular Initiating Events, Key Events, or Adverse Outcomes; and identify AOPs that contain the Molecular Initiating Events, Key Events, or Adverse Outcomes that were found in Steps 1 and 3. The process and library of informational resources proposed and tested here served as the foundation for an informational online tool (AOPERA) that helps practitioners identify their current-state knowledge gaps, navigate the four-step process, and connect to relevant resources. AOPERA can be found at https://igbb.github.io/AOPERA_HTML. Additionally, we anticipate that by simplifying and standardizing the process of linking a chemical to a known AOP, we will lower the barrier to entry for this objective and increase its accessibility to new practitioners. In turn, this may increase the demand for new or improved AOPs to which practitioners can link chemicals, thereby contributing to the expansion of the library of known AOPs.