University of Cambridge > Talks.cam > Theoretical Chemistry Informal Seminars > Assessment of broad-spectrum in vitro screening for toxicity profiling: Bioactivity space of target focussed and phenotypic assays

Assessment of broad-spectrum in vitro screening for toxicity profiling: Bioactivity space of target focussed and phenotypic assays

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2nd year PhD Talk

Traditional methods for hazard identification rely heavily on testing compounds on animals through exposure to acute and chronic repeated doses. However, these methods are economically inefficient and provide minimal information on the mechanistic background of the tested chemicals. Broad-scale in vitro screening was introduced as a potential alternative to animal testing for toxicity profiling and animal testing prioritisation. Hence, the ToxCast program was launched by the United States Environmental Protection Agency (EPA) in 2007 to adopt large scale in vitro testing through cell-free and cell-based approaches. Yet, the efficiency of in vitro screening for identifying hazards in chemicals is questionable. Here, the similarity and diversity of the dataset were investigated, giving considerable attention to compare target focussed assays against phenotypic screening. We found that target-based assays clustered together in the bioactivity space compared to the dispersed phenotypic screens. Interestingly, nuclear receptor assays, that had significant associations with toxicity in human, correlated broadly with phenotypic assay measurements. In contrast, nuclear receptor assays, with low correlations with bioactivities from phenotypic assays, had low associations with human toxicity. Based on our observations, we concluded that assay set selection is recommended to profile toxicity of a specific biological type in comparison to the utility of broad-scale in vitro measurements at a time.

This talk is part of the Theoretical Chemistry Informal Seminars series.

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