Multidimensional drug profiling by automated microscopy.

Institute of Chemistry and Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Science (Impact Factor: 31.48). 11/2004; 306(5699):1194-8. DOI: 10.1126/science.1100709
Source: PubMed

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.

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