使用自组织图谱的比较基因组杂交(CGH)数据聚类分析:在前列腺癌中的应用

T. Mattfeldt, H. Wolter, R. Kemmerling, H. Gottfried, H. Kestler
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引用次数: 30

摘要

比较基因组杂交(CGH)是一种现代遗传方法,可以对染色体失衡进行全基因组调查。对于每一个染色体区域,人们获得的信息是遗传物质的损失还是增加,或者该区域是否没有变化。通常不可能评估中期的所有46条染色体,因此对每个个体分析几个(最多20个或更多)中期,并表示为平均值。大多数情况下,人们不是单独研究一个个体,而是研究20-30个个体组成的群体。因此,大量的数据迅速积累,必须按逻辑顺序排列。在本文中,我们提出了一种自组织图谱(基因聚类)作为聚类分析工具的应用程序从pT2N0前列腺癌病例的数据由CGH研究。自组织地图是人工神经网络,具有在无监督学习规则的基础上形成集群的能力,也就是说,在我们的例子中,它只获得CGH数据作为信息(没有临床数据)。我们研究了一组40例近期未随访的病例,一组20例有随访的老年病例,并将两组的数据集合在一起。在所有组良好的聚类发现的意义上,临床相似的病例被放置到相同的集群仅基于遗传信息。数据表明,染色体臂6q、8p和13q的缺失在pT2N0前列腺癌中都很常见,但8p的缺失可能具有最大的预后重要性。
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Cluster Analysis of Comparative Genomic Hybridization (CGH) Data Using Self-Organizing Maps: Application to Prostate Carcinomas
Comparative genomic hybridization (CGH) is a modern genetic method which enables a genome‐wide survey of chromosomal imbalances. For each chromosome region, one obtains the information whether there is a loss or gain of genetic material, or whether there is no change at that region. Usually it is not possible to evaluate all 46 chromosomes of a metaphase, therefore several (up to 20 or more) metaphases are analyzed per individual, and expressed as average. Mostly one does not study one individual alone but groups of 20–30 individuals. Therefore, large amounts of data quickly accumulate which must be put into a logical order. In this paper we present the application of a self‐organizing map (Genecluster) as a tool for cluster analysis of data from pT2N0 prostate cancer cases studied by CGH. Self‐organizing maps are artificial neural networks with the capability to form clusters on the basis of an unsupervised learning rule, i.e., in our examples it gets the CGH data as only information (no clinical data). We studied a group of 40 recent cases without follow‐up, an older group of 20 cases with follow‐up, and the data set obtained by pooling both groups. In all groups good clusterings were found in the sense that clinically similar cases were placed into the same clusters on the basis of the genetic information only. The data indicate that losses on chromosome arms 6q, 8p and 13q are all frequent in pT2N0 prostatic cancer, but the loss on 8p has probably the largest prognostic importance.
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