Gamberoni Giacomo, Storari Sergio, Volinia Stefano
ENDIF-Dipartimento di Ingegneria, Università di Ferrara, Ferrara, Italy.
BMC Bioinformatics. 2006 Jan 9;7:6. doi: 10.1186/1471-2105-7-6.
Through the use of DNA microarrays it is now possible to obtain quantitative measurements of the expression of thousands of genes from a biological sample. This technology yields a global view of gene expression that can be used in several ways. Functional insight into expression profiles is routinely obtained by using Gene Ontology terms associated to the cellular genes. In this paper, we deal with functional data mining from expression profiles, proposing a novel approach that studies the correlations between genes and their relations to Gene Ontology (GO). By using this "functional correlations comparison" we explore all possible pairs of genes identifying the affected biological processes by analyzing in a pair-wise manner gene expression patterns and linking correlated pairs with Gene Ontology terms.
We apply here this "functional correlations comparison" approach to identify the existing correlations in hepatocarcinoma (161 microarray experiments) and to reveal functional differences between normal liver and cancer tissues. The number of well-correlated pairs in each GO term highlights several differences in genetic interactions between cancer and normal tissues. We performed a bootstrap analysis in order to compute false detection rates (FDR) and confidence limits.
Experimental results show the main advantage of the applied method: it both picks up general and specific GO terms (in particular it shows a fine resolution in the specific GO terms). The results obtained by this novel method are highly coherent with the ones proposed by other cancer biology studies. But additionally they highlight the most specific and interesting GO terms helping the biologist to focus his/her studies on the most relevant biological processes.
通过使用DNA微阵列,现在可以从生物样本中获得数千个基因表达的定量测量值。这项技术产生了基因表达的全局视图,可用于多种方式。通过使用与细胞基因相关的基因本体术语,通常可以获得对表达谱的功能洞察。在本文中,我们处理来自表达谱的功能数据挖掘,提出一种新颖的方法,该方法研究基因之间的相关性及其与基因本体(GO)的关系。通过使用这种“功能相关性比较”,我们探索所有可能的基因对,通过成对分析基因表达模式并将相关对与基因本体术语联系起来,确定受影响的生物过程。
我们在此应用这种“功能相关性比较”方法来识别肝癌(161个微阵列实验)中存在的相关性,并揭示正常肝脏组织和癌组织之间的功能差异。每个GO术语中相关性良好的基因对数量突出了癌组织和正常组织之间遗传相互作用的几个差异。我们进行了自举分析,以计算错误检测率(FDR)和置信限。
实验结果显示了所应用方法的主要优点:它既能挑选出一般的GO术语,也能挑选出特定的GO术语(特别是在特定的GO术语中显示出良好的分辨率)。这种新方法获得的结果与其他癌症生物学研究提出的结果高度一致。但此外,它们突出了最具体和最有趣的GO术语,有助于生物学家将其研究重点放在最相关的生物过程上。