Hupé Philippe, Stransky Nicolas, Thiery Jean-Paul, Radvanyi François, Barillot Emmanuel
Service Bioinformatique, UMR 144 CNRS/Institut Curie, 26, rue d'Ulm, Paris, 75248 cedex 05, France.
Bioinformatics. 2004 Dec 12;20(18):3413-22. doi: 10.1093/bioinformatics/bth418. Epub 2004 Sep 20.
MOTIVATION: Genomic DNA regions are frequently lost or gained during tumor progression. Array Comparative Genomic Hybridization (array CGH) technology makes it possible to assess these changes in DNA in cancers, by comparison with a normal reference. The identification of systematically deleted or amplified genomic regions in a set of tumors enables biologists to identify genes involved in cancer progression because tumor suppressor genes are thought to be located in lost genomic regions and oncogenes, in gained regions. Array CGH profiles should also improve the classification of tumors. The achievement of these goals requires a methodology for detecting the breakpoints delimiting altered regions in genomic patterns and assigning a status (normal, gained or lost) to each chromosomal region. RESULTS: We have developed a methodology for the automatic detection of breakpoints from array CGH profile, and the assignment of a status to each chromosomal region. The breakpoint detection step is based on the Adaptive Weights Smoothing (AWS) procedure and provides highly convincing results: our algorithm detects 97, 100 and 94% of breakpoints in simulated data, karyotyping results and manually analyzed profiles, respectively. The percentage of correctly assigned statuses ranges from 98.9 to 99.8% for simulated data and is 100% for karyotyping results. Our algorithm also outperforms other solutions on a public reference dataset. AVAILABILITY: The R package GLAD (Gain and Loss Analysis of DNA) is available upon request.
动机:在肿瘤进展过程中,基因组DNA区域经常会出现缺失或扩增。阵列比较基因组杂交(array CGH)技术通过与正常参考样本进行比较,使得评估癌症中DNA的这些变化成为可能。在一组肿瘤中识别出系统性缺失或扩增的基因组区域,能够帮助生物学家鉴定参与癌症进展的基因,因为肿瘤抑制基因被认为位于缺失的基因组区域,而癌基因则位于扩增的区域。阵列CGH图谱也应能改善肿瘤的分类。要实现这些目标,需要一种方法来检测界定基因组模式中改变区域的断点,并为每个染色体区域确定一个状态(正常、扩增或缺失)。 结果:我们开发了一种从阵列CGH图谱自动检测断点并为每个染色体区域确定状态的方法。断点检测步骤基于自适应权重平滑(AWS)程序,并且提供了非常有说服力的结果:我们的算法在模拟数据、核型分析结果和人工分析的图谱中分别检测到了97%、100%和94%的断点。对于模拟数据,正确确定状态的百分比范围为98.9%至99.8%,对于核型分析结果则为100%。在一个公共参考数据集上,我们的算法也优于其他解决方案。 可用性:可根据要求提供R包GLAD(DNA增益和缺失分析)。
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