Developing scientific confidence in HTS-derived prediction models: Lessons learned from an endocrine case study

Regulatory Toxicology and Pharmacology

Volumn 69, Issue 3, 2014, Pages 443-450

  Cox, Louis Anthony Tony ^a   Popken, Douglas ^a   Marty, M Sue ^b   Rowlands, J Craig ^b   Patlewicz, Grace ^c   Goyak, Katy O ^d   Becker, Richard A ^e  

^a Cox Associates ^*  (United States)

^b DOW CHEMICAL COMPANY   (United States)

^c DUPONT COMPANY   (United States)

^d EXXONMOBIL UPSTREAM RESEARCH COMPANY   (United States)

^e American Chemistry Council   (United States)

Author keywords

Adverse outcome pathways; Endocrine; High throughput high content assays; Prediction models; Validation framework

Indexed keywords

ANDROGEN; ENDOCRINE DISRUPTOR; ESTROGEN; THYROID HORMONE; POLLUTANT; STEROID;

ADVERSE OUTCOME; ARTICLE; CHEMICAL ANALYSIS; HIGH THROUGHPUT SCREENING; HUMAN; MACHINE LEARNING; NONHUMAN; PHYSICAL CHEMISTRY; PRACTICE GUIDELINE; PREDICTION; PRIORITY JOURNAL; RISK ASSESSMENT; SCREENING TEST; STEROIDOGENESIS; TOXICITY TESTING; VALIDATION PROCESS; CHEMISTRY; DRUG EFFECTS; ENDOCRINE SYSTEM; POLLUTANT; PROCEDURES; THEORETICAL MODEL; THYROID GLAND;

ANDROGENS; ENDOCRINE DISRUPTORS; ENDOCRINE SYSTEM; ENVIRONMENTAL POLLUTANTS; ESTROGENS; HIGH-THROUGHPUT SCREENING ASSAYS; HUMANS; MODELS, THEORETICAL; RISK ASSESSMENT; STEROIDS; THYROID GLAND;

EID: 84904039881     PISSN: 02732300     EISSN: 10960295     Source Type: Journal    
DOI: 10.1016/j.yrtph.2014.05.010     Document Type: Article

References (27)

1. Ankley G.T., Bennett R.S., Erickson R.J., Hoff D.J., Hornung M.W., Johnson R.D., Mount D.R., Nichols J.W., Russom C.L., Schmieder P.K., Serrrano J.A., Tietge J.E., Villeneuve D.L. Adverse outcome pathways: a conceptual framework to support ecotoxicology research and risk assessment. Environ. Toxicol. Chem. 2010, 29:730-741.
2. Becker R.A., Hays S.M., Kirman C.R., Aylward L.L., Wise K. Interpreting estrogen screening assays in the context of potency and human exposure relative to natural exposures to phytoestrogens. Birth Defects Res. B Dev. Reprod. Toxicol. 2014, 101:114-124.
3. Bhattacharya S., Zhang Q., Carmichael P.L., Boekelheide K., Andersen M.E. Toxicity testing in the 21st century: defining new risk assessment approaches based on perturbation of intracellular toxicity pathways. PLoS One 2011, 6(6):e20887.
4. Brieman L. Random forests. Mach. Learn. 2001, 45:5-32.
5. Chandler K.J., Barrier M., Jeffay S.C., Nichols H.P., Kleinstreuer N., Singh A., Reif D., Sipes N., Judson R., Dix D.J., Kavlock R.J., Hunter E.S., Knudsen T. Evaluation of 309 environmental chemicals using a mouse embryonic stem cell adherent cell differentiation and cytotoxicity assay. PLoS One 2011, 6(6):e1840.
6. Dix D.J., Houck K.A., Judson R., Kleinstreuer N., Knudsen T.B., Martin M.T., Reif D.M., Richard A.M., Shah I.A., Sipes N., Kavlock R.J. Incorporating biological, chemical and toxicological knowledge into predictive models of toxicity: Letter to the Editor. Toxicol. Sci. 2012, 130:440-441.
7. EPA, 2009. Endocrine Disruptor Screening Program; Policies and Procedures for Initial Screening. Federal Register, vol. 74, No. 71, pp. 17560-17579. (Wednesday 15.04.09). http://www.epa.gov/endo/pubs/revised_pandp_frn_041509.pdf.
8. EPA, 2011. Endocrine Disruptor Screening Program, Weight-of-Evidence: Evaluating Results of EDSP Tier 1 Screening to Identify the Need for Tier 2 Testing. http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPPT-2010-0877-0021.
9. EPA, 2013a. Prioritization of EDSP Universe of Chemicals Using Computational Toxicology Tools. http://www.regulations.gov/#!documentDetail;D=EPA-HQ-OPP-2012-0818-0022.
10. EPA, 2013b. Endocrine Disruptor Screening Program (EDSP), Weight-of-Evidence Process: Case Studies. http://www.regulations.gov/#!docketBrowser;rpp=25;po=0;dct=SR;D=EPA-HQ-OPP-2013-0230.
11. Fielden M.R., Adai A., Dunn R.T., Olaharski A., Searfoss G., Sina J., Aubrecht J., Boitier E., Nioi P., Auerbach S., Jacobson-Kram D., Raghavan N., Yang Y., Kincaid A., Sherlock J., Chen S.-J., Car B. Development and evaluation of a genomic signature for the prediction and mechanistic assessment of nongenotoxic hepatocarcinogens in the rat. Toxicol. Sci. 2011, 124:54-74. On behalf of the Predictive Safety Testing Consortium, Carcinogenicity Working Group.
12. Hartung T., Hoffmann S., Stephens M. Mechanistic validation. ALTEX 2013, 30:119-130.
13. Institute of Medicine (IOM), 2010. Evaluation of biomarkers and surrogate endpoints in chronic disease. ISBN: 978-0-309-15129-0.
14. Judson R., Kavlock R.J., Martin M.T., Reif D., Houck K.A., Knudsen T.B., Richard A.M., Tice R.R., Whelan M., Xia M., Huang R., Austin C.P., Daston G.P., Hartung T., Fowle J., Wooge W., Tong W., Dix D.J. Perspectives on validation of high-throughput assays supporting 21st century toxicity testing. ALTEX 2013, 30:51-66.
15. Kleinstreuer N., Dix D.J., Houck K.A., Kavlock R.J., Knudsen T.B., Martin M.T., Paul K.B., Reif D., Crofton K.M., Hamilton K., Hunter R., Shah I.A., Judson R. In vitro perturbations of targets in cancer hallmark processes predict rodent chemical carcinogenesis. Toxicol. Sci. 2012, 131:40-55.
16. Kleinstreuer N.D., Dix D.J., Rountree M., Baker N., Sipes N., Reif D., Spencer R., Knudsen T.B. A computational model predicting disruption of blood vessel development. PLoS Comput. Biol. 2013, 9(4):e1002996.
17. Martin M.T., Knudsen T.B., Reif D., Houck K.A., Judson R., Kavlock R.J., Dix D.J. Predictive model of rat reproductive toxicity from ToxCast high throughput screening. Biol. Reprod. 2011, 8:327-339.
18. McMullen P.D., Bhattacharya S., Woods C.G., Sun B., Yarborough K., Ross S.M., Miller M.E., McBride M., Lecluyse E.L., Clewell R.A., Andersen M.E. A map of the PPARα transcription regulatory network for primary human hepatocytes. Chem. Biol. Interact. 2014, 209:14-24.
19. National Research Council (NRC) Toxicity Testing in the 21st Century: A Vision and a Strategy 2007, National Academy Press, Washington, DC.
20. Patlewicz G., Phillips R.D., Rowlands J.C., Seidel S.D., Simon T., Goyak K., Becker R.A. Use and validation of HT/HC assays to support 21st century toxicity evaluations. Regul. Toxicol. Pharmacol. 2013, 65:259-268.
21. Reif D., Martin M.T., Tan S., Houck K.A., Judson R., Richard A.M., Knudsen T.B., Dix D.J., Kavlock R.J. Endocrine profiling and prioritization of environmental chemicals using ToxCast data. Environ. Health Perspect. 2010, 118:2-8.
22. Rotroff D.M., Dix D.J., Houck K.A., Knudsen T.B., Martin M.T., McLaurin K.W., Reif D.M., Crofton K.M., Singh A.V., Xia M., Huang R., Judson R.S. Using in vitro high throughput screening assays to identify potential endocrine disrupting chemicals. Environ. Health Perspect. 2013, 121:7-14.
23. Shah I.A., Houck K.A., Judson R., Kavlock R.J., Martin M.T., Reif D., Wambaugh J.F., Dix D.J. Using nuclear receptor activity to stratify hepatocarcinogens. PLoS One 2011, 6(2):e14584.
24. Sipes N.S., Martin M.T., Reif D.M., Kleinstreuer N.C., Judson R.S., Singh A.V., Chandler K.J., Dix D.J., Kavlock R.J., Knudsen T.B. Predictive models of prenatal developmental toxicity from ToxCast high-throughput screening data. Toxicol. Sci. 2011, 124:109-127.
25. Thomas R.S., Black M.B., Li L., Healy E., Chu T.M., Bao W., Andersen M.E., Wolfinger R.D. A comprehensive statistical analysis of predicting in vivo hazard using high-throughput in vitro screening. Toxicol. Sci. 2012, 128:398-417.
26. Thomas R.S., Philbert M.A., Auerbach S.S., Wetmore B.A., Devito M.J., Cote I., Rowlands J.C., Whelan M.P., Hays S.M., Andersen M.E., Meek M.E., Reiter L.W., Lambert J.C., Clewell H.J., Stephens M.L., Zhao Q.J., Wesselkamper S.C., Flowers L., Carney E.W., Pastoor T.P., Petersen D.D., Yauk C.L., Nong A. Incorporating new technologies into toxicity testing and risk assessment: moving from 21st century vision to a data-driven framework. Toxicol. Sci. 2013, 136:4-18.
27. Wetmore B.A., Wambaugh J.F., Ferguson S.S., Sochaski M.A., Rotroff D.M., Freeman K., Clewell H.J., Dix D.J., Andersen M.E., Houck K.A., Allen B., Judson R.S., Singh R., Kavlock R.J., Richard A.M., Thomas R.S. Integration of dosimetry, exposure, and high-throughput screening data in chemical toxicity assessment. Toxicol. Sci. 2012, 125:157-174.