Multidimensional drug profiling by automated microscopy.

Perlman, Zachary E; Slack, Michael D; Feng, Yan; Mitchison, Timothy J; Wu, Lani F; Altschuler, Steven J · Science · 2004

basic_science · Level V

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Abstract

We present a method for high-throughput cytological profiling by microscopy. Our system provides quantitative multidimensional measures of individual cell states over wide ranges of perturbations. We profile dose-dependent phenotypic effects of drugs in human cell culture with a titration-invariant similarity score (TISS). This method successfully categorized blinded drugs and suggested targets for drugs of uncertain mechanism. Multivariate single-cell analysis is a starting point for identifying relationships among drug effects at a systems level and a step toward phenotypic profiling at the single-cell level. Our methods will be useful for discovering the mechanism and predicting the toxicity of new drugs.

Medical subject headings