Integrating Publicly Available Data to Generate Computationally Predicted Adverse Outcome Pathways for Fatty Liver

Toxicological Sciences : an Official Journal of the Society of Toxicology
Shannon M BellStephen W Edwards

Abstract

Newin vitrotesting strategies make it possible to design testing batteries for large numbers of environmental chemicals. Full utilization of the results requires knowledge of the underlying biological networks and the adverse outcome pathways (AOPs) that describe the route from early molecular perturbations to an adverse outcome. Curation of a formal AOP is a time-intensive process and a rate-limiting step to designing these test batteries. Here, we describe a method for integrating publicly available data in order to generate computationally predicted AOP (cpAOP) scaffolds, which can be leveraged by domain experts to shorten the time for formal AOP development. A network-based workflow was used to facilitate the integration of multiple data types to generate cpAOPs. Edges between graph entities were identified through direct experimental or literature information, or computationally inferred using frequent itemset mining. Data from the TG-GATEs and ToxCast programs were used to channel large-scale toxicogenomics information into a cpAOP network (cpAOPnet) of over 20 000 relationships describing connections between chemical treatments, phenotypes, and perturbed pathways as measured by differential gene expression and high-throu...Continue Reading

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Citations

Apr 25, 2016·Toxicology·Noffisat O Oki, Stephen W Edwards
Sep 22, 2016·Nucleic Acids Research·Allan Peter DavisCarolyn J Mattingly
Mar 1, 2018·Environmental Toxicology and Chemistry·Dries KnapenDaniel L Villeneuve
Feb 5, 2019·Toxicological Sciences : an Official Journal of the Society of Toxicology·Nathan L PolleschJason M O'Brien
Apr 26, 2019·Toxicological Sciences : an Official Journal of the Society of Toxicology·Jeffrey J SutherlandDaniel H Robertson
May 14, 2020·International Journal of Radiation Biology·Vinita ChauhanDonald Cool
Jul 1, 2017·Archives of Toxicology·Mathieu VinkenMaurice Whelan
Mar 20, 2018·Archives of Toxicology·Fiona SewellIan Kimber
Mar 6, 2019·Toxicological Sciences : an Official Journal of the Society of Toxicology·Russell S ThomasAntony J Williams
Oct 4, 2018·Frontiers in Genetics·Alejandro Aguayo-OrozcoOlivier Taboureau
Jul 15, 2020·Toxicological Sciences : an Official Journal of the Society of Toxicology·Allan Peter DavisCarolyn J Mattingly
May 26, 2017·Environmental Toxicology and Chemistry·Carlie A LaLoneMarkus Hecker
May 11, 2020·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Ignacio J TripodiLawrence E Hunter
Oct 24, 2018·Chemical Research in Toxicology·Fredrik SvenssonAndreas Bender
May 22, 2018·Environmental Science & Technology·Kun Zhang, Yanbin Zhao
Jan 1, 2022·Toxicological Sciences : an Official Journal of the Society of Toxicology·Xi ChenZhichao Liu
Apr 22, 2018·Regulatory Toxicology and Pharmacology : RTP·Glenn J MyattCatrin Hasselgren

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