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
Cites
Cluster analysis and display of genome-wide expression patterns
Eisen, M. B., Spellman, P. T., Brown, P. O., & Botstein, D. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.25.14863 · Cited by 16,184
Functional organization of the yeast proteome by systematic analysis of protein complexes
Gavin, A., Böesche, M., Krause, R., Grandi, P., Marzioch, M., Bauer, A., Schultz, J., Rick, J. M., Michon, A., Cruciat, C., et al. (2002) · Nature · doi:10.1038/415141a · Cited by 4,729
A comprehensive analysis of protein–protein interactions in Saccharomyces cerevisiae
Uetz, P., Giot, L., Cagney, G., Mansfield, T. A., Judson, R. S., Knight, J. R., Lockshon, D., Narayan, V., Srinivasan, M., Pochart, P., et al. (2000) · Nature · doi:10.1038/35001009 · Cited by 4,706
Global analysis of protein localization in budding yeast
Huh, W.-K., Falvo, J. V., Gerke, L. C., Carroll, A. S., Howson, R. W., Weissman, J. S., & O'Shea, E. K. (2003) · Nature · doi:10.1038/nature02026 · Cited by 4,248
Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry
Ho, Y., Gruhler, A., Heilbut, A. M., Bader, G. D., Moore, L., Adams, S., Millar, A., Taylor, P. P., Bennett, K. L., Boutilier, K., et al. (2002) · Nature · doi:10.1038/415180a · Cited by 3,573
A gene expression database for the molecular pharmacology of cancer
Scherf, U., Ross, D. T., Waltham, M. C., Smith, L. H., Lee, J. K., Tanabe, L. K., Kohn, K. W., Reinhold, W. C., Myers, T. G., Andrews, D. T., et al. (2000) · Nature Genetics · doi:10.1038/73439 · Cited by 1,450
Protein Kinase Inhibitors: Insights into Drug Design from Structure
Noble, M. E. M., Endicott, J., & Johnson, L. N. (2004) · Science · doi:10.1126/science.1095920 · Cited by 1,216
An Information-Intensive Approach to the Molecular Pharmacology of Cancer
Weinstein, J. N., Myers, T. G., O'Connor, P. M., Friend, S. H., Fornace, A. J., Kohn, K. W., Fojo, T., Bates, S. E., Rubinstein, L., Anderson, N. L., et al. (1997) · Science · doi:10.1126/science.275.5298.343 · Cited by 1,183
Dynamics of the p53-Mdm2 feedback loop in individual cells
Lahav, G., Rosenfeld, N., Sigal, A., Geva‐Zatorsky, N., Levine, A. J., Elowitz, M. B., & Alon, U. (2004) · Nature Genetics · doi:10.1038/ng1293 · Cited by 1,026
Drug target validation and identification of secondary drug target effects using DNA microarrays
Marton, M. J., DeRisi, J. L., Bennett, H. A., Iyer, V. R., Meyer, M. R., Roberts, C. J., Stoughton, R. B., Burchard, J., Slade, D., Dai, H. A., et al. (1998) · Nature Medicine · doi:10.1038/3282 · Cited by 643
Chemogenomic profiling: Identifying the functional interactions of small molecules in yeast
Giaever, G. N., Flaherty, P., Kumm, J., Proctor, M. J., Nislow, C., Jaramillo, D. F., Chu, A. M., Jordan, M. I., Arkin, A. P., & Davis, R. W. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0307490100 · Cited by 506
Lum, P. Y., Armour, C. D., Stepaniants, S. B., Cavet, G., Wolf, M. K., Butler, J. S., Hinshaw, J. C., Garnier, P., Prestwich, G. D., Leonardson, A. S., et al. (2004) · Cell · doi:10.1016/s0092-8674(03)01035-3 · Cited by 478
Camptothecin: current perspectives
Thomas, C. J., Rahier, N. J., & Hecht, S. M. (2004) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2003.11.036 · Cited by 451
Anillin, a contractile ring protein that cycles from the nucleus to the cell cortex.
Field, C. M., & Alberts, B. (1995) · The Journal of Cell Biology · doi:10.1083/jcb.131.1.165 · Cited by 440
Discovering potent and selective reversible inhibitors of enzymes in complex proteomes
Leung, D., Hardouin, C., Boger, D. L., & Cravatt, B. F. (2003) · Nature Biotechnology · doi:10.1038/nbt826 · Cited by 391
Lindsay, M. A. (2003) · Nature Reviews Drug Discovery · doi:10.1038/nrd1202 · Cited by 343
Kaina, B. (2003) · Biochemical Pharmacology · doi:10.1016/s0006-2952(03)00510-0 · Cited by 328
High content screening applied to large-scale cell biology
Abraham, V. (2003) · Trends in biotechnology · doi:10.1016/j.tibtech.2003.10.012 · Cited by 288
Automatic Identification of Subcellular Phenotypes on Human Cell ArraysPreprint
Conrad, C., Erfle, H., Warnat, P., Daigle, N., Lörch, T., Ellenberg, J., Pepperkok, R., & Eils, R. (2004) · Genome Research · doi:10.1101/gr.2383804 · Cited by 222
Histone deacetylase as a new target for cancer chemotherapy
Yoshida, M., Furumai, R., Nishiyama, M., Komatsu, Y., Nishino, N., & Horinouchi, S. (2001) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s002800100300 · Cited by 217
Gunther, E. C., Stone, D. J., Gerwien, R. W., Bento, P., & Heyes, M. P. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1632587100 · Cited by 182
Paull, K. D., Lin, C. M., Malspeis, L., & Hamel, E. (1992) · PubMed · Cited by 171
Natural products as probes of cell biology: 20 years of didemnin research
Vera, M. D., & Joullié, M. M. (2002) · Medicinal Research Reviews · doi:10.1002/med.10003 · Cited by 153
Murphy, R. F., Velliste, M., & Porreca, G. (2003) · The Journal of VLSI Signal Processing Systems for Signal Image and Video Technology · doi:10.1023/b:vlsi.0000003028.71666.44 · Cited by 123
Laskin, D. L. (2002) · Toxicological Sciences · doi:10.1093/toxsci/69.2.289 · Cited by 105
SCMD: Saccharomyces cerevisiae Morphological Database
Saito, T. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkh113 · Cited by 97
Biological mechanism profiling using an annotated compound library
Root, D. E., Flaherty, S. P., Kelley, B. P., & Stockwell, B. R. (2003) · Chemistry & Biology · doi:10.1016/j.chembiol.2003.08.009 · Cited by 95
Price, J. H., Goodacre, A., Hahn, K. M., Hodgson, L., Hunter, E. A., Krajewski, S., Murphy, R. F., Rabinovich, A., Reed, J. C., & Heynen, S. (2002) · Journal of Cellular Biochemistry · doi:10.1002/jcb.10448 · Cited by 71
Haggarty, S. J., Clemons, P. A., & Schreiber, S. L. (2003) · Journal of the American Chemical Society · doi:10.1021/ja035413p · Cited by 61
Research works printed but not linked: 3
- J. H. Price et al., J. Cell. Biochem. Suppl.39, 194 (2002).
- J. G. Hardman, L. E. Limbird, A. G. Gilman, Eds., The Pharmacological Basis of Therapeutics (McGraw-Hill, New York, ed. 10, 2001), pp. 39–42.
- K. D. Paull, C. M. Lin, L. Malspeis, E. Hamel, Cancer Res.52, 3892 (1992).
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)
Lomenick, B., Hao, R., Jonai, N., Chin, R., Aghajan, M., Warburton, S., Wang, J., Wu, R. P., Gómez, F., Loo, J. A., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0910040106 · Cited by 1,130
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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