Integration of curated and high-throughput screening data to elucidate environmental influences on disease pathways.

Autor: Kosnik MB; Toxicology Program, North Carolina State University, North Carolina State University, Raleigh, NC 27695-7617, United States.; Bioinformatics Research Center, North Carolina State University, North Carolina State University, Raleigh, NC 27695-7617, United States.; Department of Biological Sciences, North Carolina State University, North Carolina State University, Raleigh, NC 27695-7617, United States., Planchart A; Toxicology Program, North Carolina State University, North Carolina State University, Raleigh, NC 27695-7617, United States.; Department of Biological Sciences, North Carolina State University, North Carolina State University, Raleigh, NC 27695-7617, United States.; Center for Human Health and the Environment, North Carolina State University, Raleigh, NC 27695-7617, United States., Marvel SW; Bioinformatics Research Center, North Carolina State University, North Carolina State University, Raleigh, NC 27695-7617, United States.; Department of Biological Sciences, North Carolina State University, North Carolina State University, Raleigh, NC 27695-7617, United States., Reif DM; Toxicology Program, North Carolina State University, North Carolina State University, Raleigh, NC 27695-7617, United States.; Bioinformatics Research Center, North Carolina State University, North Carolina State University, Raleigh, NC 27695-7617, United States.; Department of Biological Sciences, North Carolina State University, North Carolina State University, Raleigh, NC 27695-7617, United States.; Center for Human Health and the Environment, North Carolina State University, Raleigh, NC 27695-7617, United States., Mattingly CJ; Toxicology Program, North Carolina State University, North Carolina State University, Raleigh, NC 27695-7617, United States.; Department of Biological Sciences, North Carolina State University, North Carolina State University, Raleigh, NC 27695-7617, United States.; Center for Human Health and the Environment, North Carolina State University, Raleigh, NC 27695-7617, United States.
Jazyk: angličtina
Zdroj: Computational toxicology (Amsterdam, Netherlands) [Comput Toxicol] 2019 Nov; Vol. 12. Date of Electronic Publication: 2019 Jun 27.
DOI: 10.1016/j.comtox.2019.100094
Abstrakt: Addressing the complex relationship between public health and environmental exposure requires multiple types and sources of data. An important source of chemical data derives from high-throughput screening (HTS) efforts, such as the Tox21/ToxCast program, which aim to identify chemical hazard using primarily in vitro assays to probe toxicity. While most of these assays target specific genes, assessing the disease-relevance of these assays remains challenging. Integration with additional data sets may help to resolve these questions by providing broader context for individual assay results. The Comparative Toxicogenomics Database (CTD), a publicly available database that builds networks of chemical, gene, and disease information from manually curated literature sources, offers a promising solution for contextual integration with HTS data. Here, we tested the value of integrating data across Tox21/ToxCast and CTD by linking elements common to both databases (i.e., assays, genes, and chemicals). Using polymarcine and Parkinson's disease as a case study, we found that their union significantly increased chemical-gene associations and disease-pathway coverage. Integration also enabled new disease associations to be made with HTS assays, expanding coverage of chemical-gene data associated with diseases. We demonstrate how integration enables development of predictive adverse outcome pathways using 4-nonylphenol, branched as an example. Thus, we demonstrate enhancements to each data source through database integration, including scenarios where HTS data can efficiently probe chemical space that may be understudied in the literature, as well as how CTD can add biological context to those results.
Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest.
Databáze: MEDLINE
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