The DOI matches its Crossref record; 29 of the 29 references it cites were found in a registry or an index.
Multidimensional Drug Profiling By Automated Microscopy
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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“Most published HCS studies do not measure how cellular responses change as a function of compound dosage, nor do they treat cell count as an indicator of stress response14.”
From A statistical framework for high-content phenotypic profiling using cellular feature distributions (2022) · cites this paper as [14]
Citations
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Cited by
Sorted by citations
CellProfiler: image analysis software for identifying and quantifying cell phenotypes
Carpenter, A. E., Jones, T. R., Lamprecht, M. R., Clarke, C., Kang, I. H., Friman, O., Guertin, D. A., Chang, J. H., Lindquist, R. A., Moffat, J., et al. (2006) · Genome biology · doi:10.1186/gb-2006-7-10-r100 · Cited by 5,212
Cellular Heterogeneity: Do Differences Make a Difference?
Altschuler, S. J., & Wu, L. F. (2010) · Cell · doi:10.1016/j.cell.2010.04.033 · Cited by 1,214
Self-citationMulti-target therapeutics: when the whole is greater than the sum of the parts
Zimmermann, G. R., Lehár, J., & Keith, C. T. (2007) · Drug Discovery Today · doi:10.1016/j.drudis.2006.11.008 · Cited by 1,105
Target identification using drug affinity responsive target stability (DARTS)
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Target identification and mechanism of action in chemical biology and drug discovery
Schenone, M., Dančík, V., Wagner, B. K., & Clemons, P. A. (2013) · Nature Chemical Biology · doi:10.1038/nchembio.1199 · Cited by 1,147
Metadata
- 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.
- Venue
- Science
- Published
- 2004-11-12
- Volume
- 306
- Issue
- 5699
- Pages
- 1194-1198
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- 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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