Hubs in biological interaction networks exhibit low changes in expression in experimental asthma.

Hubs in biological interaction networks exhibit low changes in expression in experimental asthma.
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DOI:
10.1038/msb4100138
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发表时间:
2007
影响因子:
9.9
通讯作者:
--
中科院分区:
生物学1区
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--
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哮喘是一种涉及多基因相互作用的复杂多基因疾病。在这项研究中,我们研究了实验性哮喘的过敏反应。首先,我们使用BOND(生物分子对象网络数据库)文献策划的分子相互作用数据库构建了一个生物相互作用网络。其次,我们将微阵列数据中的差异表达基因映射到网络上。第三,我们分析了调控基因的拓扑特征。第四,利用基因本体的分类方法,分析了基因的拓扑结构与生物学功能之间的相关性。我们的研究结果表明,具有高连通性的节点(枢纽和超级枢纽)往往具有低水平的基因表达变化。我们的观察结果的意义证实了排列检验。此外,我们的分析表明,枢纽和超级枢纽有显着不同的生物功能相比,基于基因本体分类的外围节点。我们的观察对于解释基因表达数据和理解生物反应具有重要的影响。因此,我们的分析表明,差异基因表达加上拓扑特征的相互作用网络的组合提供了增强的理解,在我们的实验性哮喘模型的生物学。
Asthma is a complex polygenic disease involving the interaction of many genes. In this study, we investigated the allergic response in experimental asthma. First, we constructed a biological interaction network using the BOND (Biomolecular Object Network Databank) database of literature curated molecular interactions. Second, we mapped differentially expressed genes from microarray data onto the network. Third, we analyzed the topological characteristics of the modulated genes. Fourth, we analyzed the correlation between the topology and biological function using the Gene Ontology classifications. Our results demonstrate that nodes with high connectivity (hubs and superhubs) tend to have low levels of change in gene expression. The significance of our observations was confirmed by permutation testing. Furthermore, our analysis indicates that hubs and superhubs have significantly different biological functions compared with peripheral nodes based on Gene Ontology classification. Our observations have important ramifications for interpreting gene expression data and understanding biological responses. Thus, our analysis suggests that a combination of differential gene expression plus topological characteristics of the interaction network provides enhanced understanding of the biology in our model of experimental asthma.
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发表时间: 2001-05-03
期刊: NATURE
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