Detection of deregulated modules using deregulatory linked path.
Detection of deregulated modules using deregulatory linked path.
复制标题
使用解除管制链接路径检测解除管制模块。
DOI：
10.1371/journal.pone.0070412
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Chiu DK
中科院分区：
文献类型：
--
作者：
Hu Y;Gao L;Shi K;Chiu DK
The identification of deregulated modules (such as induced by oncogenes) is a crucial step for exploring the pathogenic process of complex diseases. Most of the existing methods focus on deregulation of genes rather than the links of the path among them. In this study, we emphasize on the detection of deregulated links, and develop a novel and effective regulatory path-based approach in finding deregulated modules. Observing that a regulatory pathway between two genes might involve in multiple rather than a single path, we identify condition-specific core regulatory path (CCRP) to detect the significant deregulation of regulatory links. Using time-series gene expression, we define the regulatory strength within each gene pair based on statistical dependence analysis. The CCRPs in regulatory networks can then be identified using the shortest path algorithm. Finally, we derive the deregulated modules by integrating the differential edges (as deregulated links) of the CCRPs between the case and the control group. To demonstrate the effectiveness of our approach, we apply the method to expression data associated with different states of Human Epidermal Growth Factor Receptor 2 (HER2). The experimental results show that the genes as well as the links in the deregulated modules are significantly enriched in multiple KEGG pathways and GO biological processes, most of which can be validated to suffer from impact of this oncogene based on previous studies. Additionally, we find the regulatory mechanism associated with the crucial gene SNAI1 significantly deregulated resulting from the activation of HER2. Hence, our method provides not only a strategy for detecting the deregulated links in regulatory networks, but also a way to identify concerning deregulated modules, thus contributing to the target selection of edgetic drugs.
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影响因子：
2.4
作者：
Ross, JS;McKenna, BJ
通讯作者：
McKenna, BJ
影响因子：
15.9
作者：
Bromberg, J
通讯作者：
Bromberg, J
影响因子：
2.3
作者：
De Wever, Olivier;Pauwels, Patrick;De Craene, Bram;Sabbah, Michele;Emami, Shahin;Redeuilh, Gerard;Gespach, Christian;Bracke, Marc;Berx, Geert
通讯作者：
Berx, Geert
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
一种用于基于基因集富集分析的差异调节路径的新型算法。
DOI：
10.1093/bioinformatics/btp510
发表时间：
2009-11-01
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Keller A;Backes C;Gerasch A;Kaufmann M;Kohlbacher O;Meese E;Lenhof HP
通讯作者：
Lenhof HP