Cited by 662Cell Image Analysis TechniquesSingle-cell and spatial transcriptomicsComputational Drug Discovery Methods

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Multidimensional Drug Profiling By Automated Microscopy

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

DOI 10.1126/science.1100709

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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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Authors: Perlman, Z. E., Slack, M. D., Feng, Y., Mitchison, T. J., Wu, L. F., & Altschuler, S. J.
Affiliations: Harvard University (US)
Corresponding author: Perlman, Zachary E.
Slack, Michael D.
Feng, Yan
Wu, Lani F.
Altschuler, Steven J.
ORCID: Mitchison, Timothy J.
Wu, Lani F.
Altschuler, Steven J.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2004-11-12
Volume: 306
Issue: 5699
Pages: 1194-1198
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.1100709
OpenAlex: W1993669821
Cited by: 660
References: 29
Citations by year: 2026: 13 · 2025: 17 · 2024: 26 · 2023: 13 · 2022: 29 · 2021: 23 · 2020: 25 · 2019: 22 · 2018: 15 · 2017: 22 · 2016: 47 · 2015: 26 · 2014: 27 · 2013: 37 · 2012: 33
FWCI: 29.15
Type: journal article
Language: en
Open access: closed
Locations: Science (publishedVersion)
PubMed (publishedVersion)
Funders: National Cancer Institute (P01CA078048)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Cell Image Analysis Techniques
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Drug Discovery › Computational Drug Discovery Methods
Keywords: drug profiling, automated microscopy, phenotypic profiling, drug target identification, mechanism of action, drug toxicity prediction, single-cell analysis, human cell culture
MeSH terms: Automation, Cell Cycle, DNA, Dose-Response Relationship, Drug, Drug Evaluation, Preclinical, Fluorescent Dyes, HeLa Cells, Humans, Image Processing, Computer-Assisted, Microscopy, Fluorescence, Pharmacology, Phenotype, Statistics as Topic, Cluster Analysis, Toxicity Tests

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Multidimensional Drug Profiling By Automated Microscopy

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