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A Gene Expression Database for the Molecular Pharmacology of Cancer
Uwe Scherf, Douglas T. Ross, Mark Waltham, Lawrence H. Smith, Jae K.
Lee, Lorraine Tanabe, Kurt W. Kohn, William C. Reinhold, Timothy G. Myers, Darren T.Andrews,
Dominic A. Scudiero, Michael B. Eisen, Edward A. Sausville, Yves Pommier, David Botstein, Patrick O. Brown,
and John N. Weinstein
Nature Genetics, volume 24, no 3 March 1st, 2000 pp:236-244
The NCI60 microarray expression project is a collaboration
between the Weinstein Laboratory at the NCI, the Brown/Botstein Laboratory at Stanford,
and the Developmental Therapeutics Program of NCI. An accompanying article from this
collaboration, Ross, et al,. Systematic variation in gene expression patterns in human
cancer cell lines. Nature Genetics 24(3): 227-234,2000 , describes
biological implications of the NCI60 gene expression patterns.
Abstract:
We used cDNA microarrays to assess gene expression profiles in 60 human cancer cell lines
of the National Cancer Institute’s drug discovery program. The accompanying paper
(Ross et al.) describes the biological implications; here, using the same
microarray data, we link the bioinformatics with chemoinformatics by correlating gene
expression and drug activity patterns in the 60 cell types. Clustering the cells on the
basis of gene expression yields a picture very different from that obtained when the cells
are clustered on the basis of their response to drugs. Gene-drug relationship for the
important clinical agents 5-fluorouracil and L-asparaginase exemplify how variations in
the transcript levels of particular genes can relate to mechanisms of drug sensitivity and
resistance. This is the first study to integrate large databases on gene expression and
molecular pharmacology.
Enlarged Figures
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Figure 1. The NCI Cancer Drug Discover - Development Pipeline
(GIF). Legend |
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Figure 2. Cluster trees of cells on the basis of genes (A) and drugs (B)
Legend |
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Figure 3. Cluster trees of drugs on the basis of cells (A) and genes (B) (GIF)
Legend |
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Figure 4. Color-coded clustered image map (CIM) relating 118 "mechanism of action" drugs to 1375 genes (GIF)
Legend |
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Figure 5. Scatter plot of L-Asparaginase (drug) and Asparagine Synthetase (gene)(GIF)
Legend |
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Table 1. Database for drugs analyzed in this study (PDF) |
Databases Used for Paper
* If you downloaded *.sit or *.sit.bin file, double click the button to generate text file.
Tools for Data Analysis and Visualization
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Generate a color-coded "Clustered Image Map" to explore
patterns of gene-gene, drug-drug, or gene-drug relationship in the
NCI60 data sets. |
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Generates color-coded Clustered Image Maps (CIMs) ("heat maps") to
represent "high-dimensional" data sets such as gene expression profiles. |
Related Links
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