A three-stage algorithm to make toxicologically relevant activity calls from quantitative high throughput screening data.

Environmental Health Perspectives
Keith R Shockley

Abstract

The ability of a substance to induce a toxicological response is better understood by analyzing the response profile over a broad range of concentrations than at a single concentration. In vitro quantitative high throughput screening (qHTS) assays are multiple-concentration experiments with an important role in the National Toxicology Program's (NTP) efforts to advance toxicology from a predominantly observational science at the level of disease-specific models to a more predictive science based on broad inclusion of biological observations. We developed a systematic approach to classify substances from large-scale concentration-​response data into statistically supported, toxicologically relevant activity categories. The first stage of the approach finds active substances with robust concentration-response profiles within the tested concentration range. The second stage finds substances with activity at the lowest tested concentration not captured in the first stage. The third and final stage separates statistically significant (but not robustly statistically significant) profiles from responses that lack statistically compelling support (i.e., "inactives"). The performance of the proposed algorithm was evaluated with simulate...Continue Reading

References

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Citations

Apr 23, 2013·Environmental Health Perspectives·Raymond R TiceJohn R Bucher
Jul 5, 2015·Toxicological Sciences : an Official Journal of the Society of Toxicology·Shiuan ChenRaymond R Tice
Jul 26, 2018·PloS One·Eric D Watt, Richard S Judson
Sep 24, 2013·Journal of Biomolecular Screening·Keith R Shockley
Apr 24, 2015·Journal of Biomolecular Screening·Jui-Hua HsiehRaymond R Tice
May 31, 2019·Frontiers in Genetics·Keith R ShockleyShyamal D Peddada
Nov 4, 2020·Chemical Research in Toxicology·Ann M RichardRaymond R Tice

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Methods Mentioned

BETA
structure activity prediction

Software Mentioned

R
R package “ caTools ”
qHTS
Linux
Windows® XP Professional Service Pack 3
INCONCLUSIVE
R R Development Core Team
R package “ drc
ACTIVE

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