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. 2010 Apr 14:11:189.
doi: 10.1186/1471-2105-11-189.

JISTIC: identification of significant targets in cancer

Felix Sanchez-Garcia  1 , Uri David Akavia, Eyal Mozes, Dana Pe'er
Affiliations

JISTIC: identification of significant targets in cancer

Felix Sanchez-Garcia et al. BMC Bioinformatics. .

Abstract

Background: Cancer is caused through a multistep process, in which a succession of genetic changes, each conferring a competitive advantage for growth and proliferation, leads to the progressive conversion of normal human cells into malignant cancer cells. Interrogation of cancer genomes holds the promise of understanding this process, thus revolutionizing cancer research and treatment. As datasets measuring copy number aberrations in tumors accumulate, a major challenge has become to distinguish between those mutations that drive the cancer versus those passenger mutations that have no effect.

Results: We present JISTIC, a tool for analyzing datasets of genome-wide copy number variation to identify driver aberrations in cancer. JISTIC is an improvement over the widely used GISTIC algorithm. We compared the performance of JISTIC versus GISTIC on a dataset of glioblastoma copy number variation, JISTIC finds 173 significant regions, whereas GISTIC only finds 103 significant regions. Importantly, the additional regions detected by JISTIC are enriched for oncogenes and genes involved in cell-cycle and proliferation.

Conclusions: JISTIC is an easy-to-install platform independent implementation of GISTIC that outperforms the original algorithm detecting more relevant candidate genes and regions. The software and documentation are freely available and can be found at: http://www.c2b2.columbia.edu/danapeerlab/html/software.html.

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Figures

Figure 1
Figure 1
GISTIC applied to example. Represented is a toy chromosome for 5 samples. The X axis corresponds to consecutive markers across the chromosome and each bar represents the G-score contribution of that marker. Two possible cut-offs determined by focal GISTIC are represented by dotted blue and red lines, these cut-offs are determined based on broad regions in other chromosomes (which are not shown in the Figure for the sake of clarity). Three results from GISTIC are contemplated: standard (A), focal based on the blue threshold (B) and focal based on the red threshold (C). Reported peaks are displayed as green bars at the top, Focal GISTIC's ability to capture additional peaks is dependent on the threshold determined by aberrations in other chromosomes.
Figure 2
Figure 2
Limited peel-off applied to example. Limited peel-off for the same example shown in Figure 1. The x axis corresponds to consecutive markers across the chromosome while each bar represents the G-score contribution of that marker. Reported peaks are displayed as green bars at the top. Limited peel-off successfully detects two peaks in the example, independently of aberrations in other chromosomes. The figure also illustrates how thresholds in limited peel-off are applied. In this example s = 1. (A) The G-score contribution for each sample is decomposed into the G-score for the primary peak (green), Gr (white) and Gn (red). (B) Each bar illustrates the total Gn of the marker. The threshold Gthres represents the cut-off that determines whether the peel-off should be aborted. In this example the peel-off is aborted in marker 14, allowing the detection of an additional peak.
Figure 3
Figure 3
Amplification aberrations for chromosome 19. Represented are standard (A), focal (B) and limited peel-off (C) results for amplifications in the whole chromosome 19. The x axis corresponds to consecutive markers across the chromosome and the y axis corresponds to the q-value in logarithmic scale. The significance threshold for aberrations (q-value = 0.25) is represented by a blue line. Reported peak regions are illustrated in green. Limited peel-off detects 6 novel peaks.
Figure 4
Figure 4
Deletion aberrations for chromosome 22. Represented are standard (A), focal (B) and limited peel-off (C) results for deletions in the whole chromosome 22. The x axis corresponds to consecutive markers across the chromosome and the y axis corresponds to the q-value in logarithmic scale. Note that only markers for which data is available are plotted. The significance threshold for aberrations (q-value = 0.25) is represented by a blue line. Reported peak regions are illustrated in green. Limited peel-off detects 3 novel peaks.
Figure 5
Figure 5
IGV display of JISTIC results. Segmented copy number and JISTIC results can be simultaneously displayed using the visualization tool IGV [20]. The main window displays the segmented copy number data used as JISTIC input. Two tracks at the bottom show JISTIC's output (G-score and peak regions respectively).
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