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Differentiating Pathway-Specific From Nonspecific Effects in High-Throughput Toxicity Data: A Foundation for Prioritizing Adverse Outcome Pathway Development

Metadata Updated: November 12, 2020

Previous work identified a ‘cytotoxic burst’ (CTB) phenomenon wherein large numbers of the ToxCast assays begin to respond at or near test chemical concentrations that elicit cytotoxicity, and a statistical approach to defining the bounds of the CTB was developed. To focus AOP development on the molecular targets corresponding to ToxCast assays indicating pathway-specific effects, we conducted a meta-analysis to identify which assays most frequently respond at concentrations below the CTB. A preliminary list of potentially important, target-specific assays was determined by ranking assays by the fraction of chemical hits below the CTB compared to the number of chemicals tested. Additional priority assays were identified using a diagnostic-odds-ratio approach which gives greater ranking to assays with high specificity but low responsivity. Combined, the two prioritization methods identified several novel targets (e.g., peripheral benzodiazepine and progesterone receptors) to prioritize for AOP development, and affirmed the importance of a number of existing AOPs aligned with ToxCast targets (e.g., thyroperoxidase, estrogen receptor, aromatase).

This dataset is associated with the following publication: Fay, K., J. Swintek, D. Villeneuve, S. Edwards, M. Nelms, B. Blackwell, and G. Ankley. Differentiating pathway-specific from non-specific effects in high-throughput toxicity data: A foundation for prioritizing adverse outcome pathway development. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 163(2): 500-515, (2018).

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Public: This dataset is intended for public access and use. License: See this page for license information.

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Metadata Created Date November 12, 2020
Metadata Updated Date November 12, 2020

Metadata Source

Harvested from EPA ScienceHub

Additional Metadata

Resource Type Dataset
Metadata Created Date November 12, 2020
Metadata Updated Date November 12, 2020
Publisher U.S. EPA Office of Research and Development (ORD)
Data Last Modified 2018-04-30
Public Access Level public
Bureau Code 020:00
Schema Version
Harvest Object Id 09a1f096-b5e2-45e4-9e9b-0afae4d42180
Harvest Source Id 04b59eaf-ae53-4066-93db-80f2ed0df446
Harvest Source Title EPA ScienceHub
Program Code 020:095
Publisher Hierarchy U.S. Government > U.S. Environmental Protection Agency > U.S. EPA Office of Research and Development (ORD)
Related Documents
Source Datajson Identifier True
Source Hash 345a5d20832ddd025d5dffefe7a4c9d120a11352
Source Schema Version 1.1

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