a statistical framework for differential network analysis from microarray data统计从微阵列数据微分网络分析框架.pdfVIP

Gill et al. BMC Bioinformatics 2010, 11:95 /1471-2105/11/95 METHODOLOGY ARTICLE Open Access A statistical framework for differential network analysis from microarray data 1 2 2* Ryan Gill , Somnath Datta , Susmita Datta Abstract Background: It has been long well known that genes do not act alone; rather groups of genes act in consort during a biological process. Consequently, the expression levels of genes are dependent on each other. Experimental techniques to detect such interacting pairs of genes have been in place for quite some time. With the advent of microarray technology, newer computational techniques to detect such interaction or association between gene expressions are being proposed which lead to an association network. While most microarray analyses look for genes that are differentially expressed, it is of potentially greater significance to identify how entire association network structures change between two or more biological settings, say normal versus diseased cell types. Results: We provide a recipe for conducting a differential analysis of networks constructed from microarray data under two experimental settings. At the core of our approach lies a connectivity score that represents the strength of genetic association or interaction between two genes. We use this score to propose formal statistical tests for each of following queries: (i) whether the overall modular structures of the two networks are different, (ii) whether the connectivity of a particular set of “interesting genes” has changed between the two networks, and (iii) whether the connectivity of a given single gene has changed between the two networks. A number of examples of this score is provided. We carried out our method on two types of simulated data: Gaussian networks and netw