Use of cell viability assay data improves the prediction accuracy of conventional quantitative structure-activity relationship models of animal carcinogenicity.
BACKGROUND: To develop efficient approaches for rapid evaluation of chemical toxicity and human health risk of environmental compounds, the National Toxicology Program (NTP) in collaboration with the National Center for Chemical Genomics has initiated a project on high-throughput screening (HTS) of...
| Published in: | Environmental Health Perspectives Vol. 116; no. 4; pp. 506 - 514 |
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| Main Authors: | , , , |
| Format: | equations & formulas research tables/charts Journal Article |
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National Institute of Environmental Health Sciences
Apr2008
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=105763753&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 105763753 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00916765 3B5 jtl: Environmental Health Perspectives issn: 00916765 maglogo: N pubinfo: dt: Apr2008 vid: 116 iid: 4 pid: 56539 pub: National Institute of Environmental Health Sciences place: Research Triangle Park, North Carolina artinfo: ui: 105763753 105763753 2009892239 10.1289/ehp.10573 NLM18414635 105763753 ppf: 506 ppct: 8 formats: fmt: @attributes: type: P tig: atl: Use of cell viability assay data improves the prediction accuracy of conventional quantitative structure-activity relationship models of animal carcinogenicity. aug: au: Zhu H Rusyn I Richard A Tropsha A affil: Carolina Environmental Bioinformatics Research Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA sug: subj: Biological Assay Carcinogens Analysis Environmental Pollutants Analysis Toxicity Tests Animal Studies Funding Source Rodents ab: BACKGROUND: To develop efficient approaches for rapid evaluation of chemical toxicity and human health risk of environmental compounds, the National Toxicology Program (NTP) in collaboration with the National Center for Chemical Genomics has initiated a project on high-throughput screening (HTS) of environmental chemicals. The first HTS results for a set of 1,408 compounds tested for their effects on cell viability in six different cell lines have recently become available via PubChem. OBJECTIVES: We have explored these data in terms of their utility for predicting adverse health effects of the environmental agents. METHODS AND RESULTS: Initially, the classification [kappa] nearest neighbor ([kappa]NN) quantitative structure- activity relationship (QSAR) modeling method was applied to the HTS data only, for a curated data set of 384 compounds. The resulting models had prediction accuracies for training, test (containing 275 compounds together), and external validation (109 compounds) sets as high as 89%, 71%, and 74%, respectively. We then asked if HTS results could be of value in predicting rodent carcinogenicity. We identified 383 compounds for which data were available from both the Berkeley Carcinogenic Potency Database and NTP-HTS studies. We found that compounds classified by HTS as 'actives' in at least one cell line were likely to be rodent carcinogens (sensitivity 77%); however, HTS 'inactives' were far less informative (specificity 46%). Using chemical descriptors only, [kappa]NN QSAR modeling resulted in 62.3% prediction accuracy for rodent carcinogenicity applied to this data set. Importantly, the prediction accuracy of the model was significantly improved (72.7%) when chemical descriptors were augmented by HTS data, which were regarded as biological descriptors. CONCLUSIONS: Our studies suggest that combining NTP-HTS profiles with conventional chemical descriptors could considerably improve the predictive power of computational approaches in toxicology. pubtype: Academic Journal doctype: equations & formulas research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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