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Multidimensional drug profiling by automated microscopy.

Zachary E Perlman·Michael D Slack·Yan Feng·Timothy J Mitchison·Lani F Wu·Steven J Altschuler
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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.

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AutomationCell CycleCluster AnalysisDNADose-Response Relationship, DrugDrug Evaluation, PreclinicalFluorescent DyesHeLa CellsHumansImage Processing, Computer-AssistedMicroscopy, FluorescencePharmacologyPhenotypeStatistics as TopicToxicity TestsJournal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.

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Zachary E Perlman, Michael D Slack, Yan Feng, Timothy J Mitchison, Lani F Wu, Steven J Altschuler. 2004-11-12. Multidimensional drug profiling by automated microscopy.. https://doi.org/10.1126/science.1100709

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