Multidimensional Drug Profiling By Automated Microscopy

Author:

Perlman Zachary E.123,Slack Michael D.123,Feng Yan123,Mitchison Timothy J.123,Wu Lani F.123,Altschuler Steven J.123

Affiliation:

1. Institute of Chemistry and Cell Biology, Harvard Medical School, Boston, MA 02115, USA.

2. Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.

3. Bauer Center for Genomics Research, Harvard University, Cambridge, MA 02138, USA.

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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