Figure 1.
Web-based tool for accessing the four-platform aCGH data.
A. The tool can be accessed at the CellMiner website by clicking on the “NCI-60 Analysis tools” tab (boxed in red). In this example, 3 cancer-associated genes are queried simultaneously: CDKN2A, CCNE1 and KRAS. B. The output includes a bar plot of the estimated copy number for each cell line. The x-axis is the DNA copy number. The y-axis shows the cell lines, with the bars colored based on tissue of origin. Bars to the left of 2N indicate loss whereas bars to the right indicate genomic gain. Dotted lines indicate cell lines with copy number gains in CCNE1 and KRAS C. A scatter plot is also provided for each cell line. The x-axis shows the chromosomal location. The y-axis shows the log2 intensity values on the left. The red dots indicate probes that fall within the gene. The blue dots indicate the flanking regions. The data are received as Excel files. See text for details.
Figure 2.
Example of integrated analysis using CellMiner.
The leftmost plot shows a barplot of copy number values for CDKN2A obtained by querying CellMiner. The middle plot shows the gene expression and the rightmost plot shows the response to a Mitoxantrone, a drug with significant negative correlation with the copy number status of CDKN2A. Dotted lines indicate some of the cell lines where the direction of copy number alteration is in the same direction as the gene expression and in the opposite direction as the drug activity.
Figure 3.
Whole genome visualization of aCGH results for the NCI-60.
The x-axis is the chromosomal location of the probes, colored by chromosome number and ordered by genomic position. The y-axis is the log ratio of the probe intensities. The black horizontal marks indicate the average log2 copy numbers in each segment, as calculated by Circular Binary Segmentation (see Materials and Methods). The amount of scatter above and below the segments’ black marks indicates the level of probe variability. The locations of some cancer-related genes that have focal gains or losses are also indicated. High-resolution images for all the NCI-60 cell lines are available in Figure S1 and at our Website [21].
Table 1.
Two measures of the genomic instability of the cell linesa.
Table 2.
Focal alterations and correlation between copy number alteration and expression for known tumor suppressors.
Figure 4.
Plots of probe intensities and segmented averages for cancer interesting genes.
A. CDKN2A and flanking sequence on chromosome nine for six cell lines. The central vertical lilac region delineates the gene location. B. MYC and flanking sequence on chromosome eight for five cell lines. The central vertical lilac region delineates the gene location. C. ABCB1 (MDR1), ABCB4 and flanking sequence on chromosome 7 for the parental OVCAR_8 and its drug-resistant derivative NCI_ADR_RES. The green and pink central vertical regions delineate the locus of ABCB1 and ABCC4, respectively. In A, B, and C the x-axis is the nucleotide location. The y-axis values on the left are the average log intensity ratios, and on the right are estimated DNA copy numbers. The black horizontal lines show the average log intensity ratio in each segment while the brown points show the log intensity ratios for each probe.
Figure 5.
Correlation between DNA copy number alterations and transcript expression for all genes.
Histogram of the Pearson’s correlations between copy number and gene expression for the complete set of 18,504 genes with both values available. The lower and upper sets of tick marks above the x-axis show the correlations for individual oncogenes (in red) and tumor-suppressors (in blue), respectively.
Table 3.
Selected known and putative tumor suppressors.