Source:http://linkedlifedata.com/resource/pubmed/id/21216932
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
2011-2-10
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pubmed:abstractText |
High-content screening is increasingly used to elucidate changes in cellular biology arising from treatment with small molecules and biological probes. We describe a cell classifier for automated analysis of multiparametric data from immunofluorescence microscopy and characterize the phenotypes of 41 cell-cycle modulators, including several protein kinase inhibitors in preclinical and clinical development. This method produces a consistent assessment of treatment-induced phenotypes across experiments done by different biologists and highlights the prevalence of nonuniform and concentration-dependent cellular response to treatment. Contrasting cell phenotypes from high-content screening to kinase selectivity profiles from cell-free assays highlights the limited utility of enzyme potency ratios in understanding the mechanism of action for cell-cycle kinase inhibitors. Our cell-level approach for assessing phenotypic outcomes is reliable, reproducible and capable of supporting medium throughput analyses of a wide range of cellular perturbations.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1538-8514
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
10
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
242-54
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pubmed:meshHeading |
pubmed-meshheading:21216932-Antineoplastic Agents,
pubmed-meshheading:21216932-Cell Cycle,
pubmed-meshheading:21216932-Cell Proliferation,
pubmed-meshheading:21216932-Cells,
pubmed-meshheading:21216932-Decision Trees,
pubmed-meshheading:21216932-Dose-Response Relationship, Drug,
pubmed-meshheading:21216932-HCT116 Cells,
pubmed-meshheading:21216932-Humans,
pubmed-meshheading:21216932-Microscopy, Fluorescence,
pubmed-meshheading:21216932-Microtubules,
pubmed-meshheading:21216932-Phenotype,
pubmed-meshheading:21216932-Protein Kinase Inhibitors,
pubmed-meshheading:21216932-Protein-Serine-Threonine Kinases,
pubmed-meshheading:21216932-Reproducibility of Results
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pubmed:year |
2011
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pubmed:articleTitle |
A robust high-content imaging approach for probing the mechanism of action and phenotypic outcomes of cell-cycle modulators.
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pubmed:affiliation |
Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. sutherlandje@lilly.com
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pubmed:publicationType |
Journal Article
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