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2000 Publication

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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

Full text (PDF) Enlarged figures Gene database used for the paper Tools for data analysis and visualization Related links

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
Graphic Figure 1. The NCI Cancer Drug Discover - Development Pipeline (GIF). Legend
Graphic Figure 2. Cluster trees of cells on the basis of genes (A) and drugs (B)   Legend
Graphic Figure 3. Cluster trees of drugs on the basis of cells (A) and genes (B) (GIF)  Legend
Graphic Figure 4. Color-coded clustered image map (CIM) relating 118 "mechanism of action" drugs to 1375 genes  (GIF)   Legend
Graphic Figure 5. Scatter plot of L-Asparaginase (drug) and Asparagine Synthetase (gene)(GIF)   Legend
Table 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.
Dataset Drug activity data (A-matrix), tab delimited (1400 drugs x 60 cells)    (687 Kb)
  Description   *** UPDATED 12/19/01 ***   (Download compressed:   gz format   Mac)   (previous version)
Dataset Drug activity data of 118 "Mechanism of Action" drugs, tab delimited (118 drugs x 60 cells ) (33 Kb) Description *** UPDATED 12/19/01 ***   (Download compressed:   gz format   Mac)   (previous version)
Dataset Gene expression data (T-matrix), tab delimited (1375 genes x 60 cells)    (579 Kb)   Description  *** UPDATED 12/19/01 ***   (Download compressed:   gz format)   (previous version)
Dataset Target matrix (15 Kb)
  Description  *** UPDATED 01/09/02 ***   (Download compressed:   gz format)
Dataset Gene expression data (all genes, 9,706), tab delimited  (9,706 genes x 60 cells )   (6.4 MB)
  Description   *** UPDATED 12/19/01 ***   (Download compressed:   gz format   Mac)   (previous version)
Dataset Gene-drug correlation data (AT-matrix), tab delimited (1375 genes x 118 drugs)   (1.1 Mb)
  Description  (Download compressed: gz format   Mac)
Tools for Data Analysis and Visualization
CIM for NCI60 Generate a color-coded "Clustered Image Map" to explore patterns of gene-gene, drug-drug, or gene-drug relationship in the NCI60 data sets.
CIMminer Generates color-coded Clustered Image Maps (CIMs) ("heat maps") to represent "high-dimensional" data sets such as gene expression profiles.
Related Links
Nature Genetics
Stanford Genomic Resources
The NCI Developmental Therapeutics Program
Gene Chips microarray review site

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