title: Accelerating Adverse Outcome Pathway Development Using Publicly Available Data Sources.
abstract: The adverse outcome pathway (AOP) concept links molecular perturbations with organism and population-level outcomes to support high-throughput toxicity (HTT) testing. International efforts are underway to define AOPs and store the information supporting these AOPs in a central knowledge base; however, this process is currently labor-intensive and time-consuming. Publicly available data sources provide a wealth of information that could be used to define computationally predicted AOPs (cpAOPs), which could serve as a basis for creating expert-derived AOPs in a much more efficient way. Computational tools for mining large datasets provide the means for extracting and organizing the information captured in these public data sources. Using cpAOPs as a starting point for expert-derived AOPs should accelerate AOP development. Coupling this with tools to coordinate and facilitate the expert development efforts will increase the number and quality of AOPs produced, which should play a key role in advancing the adoption of HTT testing, thereby reducing the use of animals in toxicity testing and greatly increasing the number of chemicals that can be tested.
authors.affiliation: Oak Ridge Institute for Science and Education, Oak Ridge, TN, USA.|Integrated Systems Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, 109 T.W. Alexander Drive, Mail Code: B305-01, Research Triangle Park, NC, 27709, USA.
authors.forename: Noffisat O
authors.initials: NO
authors.lastname: Oki
authors.affiliation: Oak Ridge Institute for Science and Education, Oak Ridge, TN, USA.|Integrated Systems Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, 109 T.W. Alexander Drive, Mail Code: B305-01, Research Triangle Park, NC, 27709, USA.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Nelms
authors.affiliation: Oak Ridge Institute for Science and Education, Oak Ridge, TN, USA.|Integrated Systems Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, 109 T.W. Alexander Drive, Mail Code: B305-01, Research Triangle Park, NC, 27709, USA.|ILS/Contractor Supporting the NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM), Research Triangle Park, NC, USA.
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Bell
authors.affiliation: Genomics Research Core, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC, USA.
authors.forename: Holly M
authors.initials: HM
authors.lastname: Mortensen
authors.affiliation: Integrated Systems Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, 109 T.W. Alexander Drive, Mail Code: B305-01, Research Triangle Park, NC, 27709, USA. edwards.stephen@epa.gov.
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Edwards
mesh_terms: D003198:Computer Simulation; D054750:Ecotoxicology / Q000379:methods*; D006801:Humans; D019451:Information Management / Q000379:methods*; D018570:Risk Assessment / Q000379:methods; D018675:Toxicity Tests
keywords: Adverse outcome pathways (AOPs); Computationally predicted AOPs (cpAOPs); Data mining; Risk assessment; Toxicity pathways
references.citation: Nucleic Acids Res. 2015 Jan;43(Database issue):D914-20
references.pmid: 25326323
references.citation: Environ Health Perspect. 2009 Mar;117(3):392-9
references.pmid: 19337514
references.citation: Environ Toxicol Chem. 2010 Mar;29(3):730-41
references.pmid: 20821501
references.citation: Nucleic Acids Res. 2015 Jan;43(Database issue):D1113-6
references.pmid: 25361974
references.citation: Nucleic Acids Res. 2000 Jan 1;28(1):27-30
references.pmid: 10592173
references.citation: Nucleic Acids Res. 2004 Jan 1;32(Database issue):D91-4
references.pmid: 14681366
references.citation: Wiley Interdiscip Rev Syst Biol Med. 2009 Nov-Dec;1(3):390-9
references.pmid: 20052305
references.citation: Genome Biol. 2010;11(8):R86
references.pmid: 20738864
references.citation: Clin Pharmacol Ther. 2012 Oct;92(4):414-7
references.pmid: 22992668
references.citation: Nucleic Acids Res. 2015 Jan;43(Database issue):D726-36
references.pmid: 25348401
references.citation: Nucleic Acids Res. 2006 Jan 1;34(Database issue):D668-72
references.pmid: 16381955
references.citation: Nucleic Acids Res. 2015 Jul 1;43(W1):W589-98
references.pmid: 25897122
references.citation: Nucleic Acids Res. 2014 Jan;42(Database issue):D789-93
references.pmid: 24194605
references.citation: Regul Toxicol Pharmacol. 2014 Dec;70(3):629-40
references.pmid: 25261300
references.citation: Nucleic Acids Res. 2006 Jan 1;34(Database issue):D535-9
references.pmid: 16381927
references.citation: Nucleic Acids Res. 2014 Jan;42(Database issue):D818-24
references.pmid: 24163257
references.citation: PLoS One. 2014 Nov 07;9(11):e112193
references.pmid: 25380136
references.citation: J Biotechnol. 2005 Sep 29;119(3):219-44
references.pmid: 16005536
references.citation: Nucleic Acids Res. 2013 Jan;41(Database issue):D801-7
references.pmid: 23161693
references.citation: Environ Health Perspect. 2011 Nov;119(11):1596-603
references.pmid: 21788198
references.citation: Nucleic Acids Res. 2013 Jan;41(Database issue):D377-86
references.pmid: 23193289
references.citation: Nat Rev Drug Discov. 2009 Apr;8(4):286-95
references.pmid: 19337271
references.citation: Nucleic Acids Res. 2005 Jan 1;33(Database issue):D514-7
references.pmid: 15608251
references.citation: Mamm Genome. 2015 Aug;26(7-8):314-24
references.pmid: 25939429
references.citation: Environ Toxicol Chem. 2011 Jan;30(1):22-38
references.pmid: 20963852
references.citation: Environ Health Perspect. 2015 Nov;123(11):1193-9
references.pmid: 25859761
references.citation: J Biomed Semantics. 2014 Jun 03;5(Suppl 1 Proceedings of the Bio-Ontologies Spec Interest G):S5
references.pmid: 25093074
references.citation: Nucleic Acids Res. 2002 Jan 1;30(1):207-10
references.pmid: 11752295
references.citation: Nucleic Acids Res. 2007 Jan;35(Database issue):D696-9
references.pmid: 16982638
references.citation: Chemosphere. 2015 Feb;120:764-77
references.pmid: 25439131
references.citation: Regul Toxicol Pharmacol. 2015 Aug;72(3):514-37
references.pmid: 25863193
references.citation: Nat Methods. 2015 Feb;12(2):115-21
references.pmid: 25633503
references.citation: Nucleic Acids Res. 2013 Jan;41(Database issue):D854-60
references.pmid: 23074187
references.citation: Nucleic Acids Res. 2015 Jan;43(Database issue):D921-7
references.pmid: 25313160
references.citation: Cancers (Basel). 2012 Nov 08;4(4):1180-211
references.pmid: 24213504
references.citation: Genome Res. 2005 Oct;15(10):1451-5
references.pmid: 16169926
references.citation: Environ Health Perspect. 2010 Apr;118(4):485-92
references.pmid: 20368123
references.citation: Curr Protoc Mol Biol. 2010 Jan;Chapter 19:Unit 19.10.1-21
references.pmid: 20069535
references.citation: Eur J Hum Genet. 2014 Jan;22(1):144-7
references.pmid: 23695286
references.citation: Environ Sci Technol. 2015 Jan 6;49(1):3-9
references.pmid: 25469516
references.citation: Toxicol Sci. 2014 Dec;142(2):321-30
references.pmid: 25466379
references.citation: Nucleic Acids Res. 2015 Jan;43(Database issue):D117-22
references.pmid: 25378322
references.citation: Nucleic Acids Res. 2015 Jan;43(Database issue):D1049-56
references.pmid: 25428369
references.citation: BMC Bioinformatics. 2006 Mar 28;7:176
references.pmid: 16569235
references.citation: Nucleic Acids Res. 2015 Jan;43(Database issue):D690-7
references.pmid: 25398896
references.citation: Eur J Nucl Med Mol Imaging. 2012 Sep;39(9):1492-6
references.pmid: 22790876
references.citation: Toxicol Sci. 2008 Dec;106(2):312-8
references.pmid: 18791183
references.citation: PLoS Comput Biol. 2013 Apr;9(4):e1002996
references.pmid: 23592958
references.citation: Nucleic Acids Res. 2014 Jan;42(Database issue):D199-205
references.pmid: 24214961