Aggregating data for computational toxicology applications: The U.S. Environmental Protection Agency (EPA) Aggregated Computational Toxicology Resource (ACToR) System - PubMed (original) (raw)

Review

doi: 10.3390/ijms13021805. Epub 2012 Feb 9.

Matthew T Martin 1, Peter Egeghy 2, Sumit Gangwal 1, David M Reif 1, Parth Kothiya 1, Maritja Wolf 3, Tommy Cathey 3, Thomas Transue 3, Doris Smith 1, James Vail 1, Alicia Frame 1, Shad Mosher 1, Elaine A Cohen Hubal 1, Ann M Richard 1

Affiliations

Review

Aggregating data for computational toxicology applications: The U.S. Environmental Protection Agency (EPA) Aggregated Computational Toxicology Resource (ACToR) System

Richard S Judson et al. Int J Mol Sci. 2012.

Abstract

Computational toxicology combines data from high-throughput test methods, chemical structure analyses and other biological domains (e.g., genes, proteins, cells, tissues) with the goals of predicting and understanding the underlying mechanistic causes of chemical toxicity and for predicting toxicity of new chemicals and products. A key feature of such approaches is their reliance on knowledge extracted from large collections of data and data sets in computable formats. The U.S. Environmental Protection Agency (EPA) has developed a large data resource called ACToR (Aggregated Computational Toxicology Resource) to support these data-intensive efforts. ACToR comprises four main repositories: core ACToR (chemical identifiers and structures, and summary data on hazard, exposure, use, and other domains), ToxRefDB (Toxicity Reference Database, a compilation of detailed in vivo toxicity data from guideline studies), ExpoCastDB (detailed human exposure data from observational studies of selected chemicals), and ToxCastDB (data from high-throughput screening programs, including links to underlying biological information related to genes and pathways). The EPA DSSTox (Distributed Structure-Searchable Toxicity) program provides expert-reviewed chemical structures and associated information for these and other high-interest public inventories. Overall, the ACToR system contains information on about 400,000 chemicals from 1100 different sources. The entire system is built using open source tools and is freely available to download. This review describes the organization of the data repository and provides selected examples of use cases.

Keywords: ACToR; DSSTox; ExpoCastDB; ToxCastDB; ToxRefDB; computational toxicology; database; exposure; hazard; high-throughput screening.

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Figures

Figure 1

Figure 1

Organization of the databases. ACToR and the affiliated EPA databases shown use the same chemical identity and structure tables, fed by the DSSTox project (at left). Content from external data sources are fed into the ACToR database after filtering and formatting (bottom), with structures provided by PubChem if not available in DSSTox.

Figure 2

Figure 2

Illustration of assay categories used in ACToR. Assays (data sets) are put into one or more categories in this hierarchy to allow users to select only certain relevant types of data. This table shows the top level of this category hierarchy.

Figure 3

Figure 3

Screen shot from the ACToR web site for the high level view of data available for a set of chemicals. The view shows the chemical structure, name and CASRN, plus an indication of the types of data available for the chemical. In particular, we call out key phenotype categories (See Figure 2) and exposure. A red box in a column indicates that the database contains data for that chemical-category combination, and not that (for instance) the chemical causes cancer.

Figure 4

Figure 4

Screen shot of a portion of the ACToR data for Zinc dibutyldithiocarbamate

Figure 5

Figure 5

Screen shot from the ToxRefDB web site for the high level view of data available for a set of chemicals across the various available study types. This view is similar to the summary for ACToR (Figure 3), except that it indicates they standard types of studies for which the chemical has data in ToxRefDB.

Figure 6

Figure 6

Screen shot from the ToxRefDB web site of the Endpoint search page with the search criteria and additional field information to be included.

Figure 7

Figure 7

Screen shot from the ToxRefDB web site of the Endpoint search page with the results of the search displayed.

Figure 8

Figure 8

Data levels and processing steps in the ToxCast data workflow.

Figure 9

Figure 9

ExpoCastDB descriptive statistic chemical concentration results in different media for chloropyrifos.

Figure 10

Figure 10

Summary of fraction of chemicals in the targeted inventory having exposure data by exposure category.

References

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    1. Judson R., Richard A., Dix D., Houck K., Elloumi F., Martin M., Cathey T., Transue T.R., Spencer R., Wolf M. ACToR—Aggregated Computational Toxicology Resource. Toxicol. Appl. Pharmacol. 2008;233:7–13. - PubMed

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