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Prediction of human population responses to toxic compounds by a collaborative competition
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The NIEHS-NCATS-UNC DREAM Toxicogenetics Collaboration (Including:
). (2015) Prediction of human population responses to toxic compounds by a collaborative competition. Nature Biotechnology, 33 (9). pp. 933-940. doi:10.1038/nbt.3299![[img]](http://wrap.warwick.ac.uk/style/images/fileicons/application_pdf.png) |
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Official URL: http://dx.doi.org/10.1038/nbt.3299
Abstract
The ability to computationally predict the effects of toxic compounds on humans could help address the deficiencies of current chemical safety testing. Here, we report the results from a community-based DREAM challenge to predict toxicities of environmental compounds with potential adverse health effects for human populations. We measured the cytotoxicity of 156 compounds in 884 lymphoblastoid cell lines for which genotype and transcriptional data are available as part of the Tox21 1000 Genomes Project. The challenge participants developed algorithms to predict interindividual variability of toxic response from genomic profiles and population-level cytotoxicity data from structural attributes of the compounds. 179 submitted predictions were evaluated against an experimental data set to which participants were blinded. Individual cytotoxicity predictions were better than random, with modest correlations (Pearson's r < 0.28), consistent with complex trait genomic prediction. In contrast, predictions of population-level response to different compounds were higher (r < 0.66). The results highlight the possibility of predicting health risks associated with unknown compounds, although risk estimation accuracy remains suboptimal.
| Item Type: | Journal Article | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Subjects: | R Medicine > RA Public aspects of medicine | ||||||||
| Divisions: | Faculty of Science > Statistics Faculty of Science > Centre for Systems Biology |
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| Library of Congress Subject Headings (LCSH): | Poisons | ||||||||
| Journal or Publication Title: | Nature Biotechnology | ||||||||
| Publisher: | Nature Publishing Group | ||||||||
| ISSN: | 1087-0156 | ||||||||
| Official Date: | 10 August 2015 | ||||||||
| Dates: |
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| Volume: | 33 | ||||||||
| Number: | 9 | ||||||||
| Number of Pages: | 8 | ||||||||
| Page Range: | pp. 933-940 | ||||||||
| DOI: | 10.1038/nbt.3299 | ||||||||
| Status: | Peer Reviewed | ||||||||
| Publication Status: | Published | ||||||||
| Access rights to Published version: | Open Access | ||||||||
| Funder: | National Institutes of Health (U.S.) (NIH), National Institute of Environmental Health Sciences (NIEHS), United States. Environmental Protection Agency, Europæiske molekylærbiologiske laboratorium. Outstation at DESY (EMBL), European Union (EU) | ||||||||
| Grant number: | RD83516601, RD83382501, R01CA161608 (NIH), R01HG006292 (NIH), 5R01CA152301 (NIH), 1R01CA172211 (NIH) |
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