Detection of characteristic sub pathway network for angiogenesis based on the comprehensive pathway network
Detection of characteristic sub pathway network for angiogenesis based on the comprehensive pathway network
复制标题
基于综合通路网络的血管生成特征子通路网络检测
DOI：
10.1186/1471-2105-11-s1-s32
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发表时间：
2010-01-01
影响因子：
3
通讯作者：
Li, Shao
中科院分区：
文献类型：
--
作者：
Huang, Yezhou;Li, Shao
背景生物系统中的各种途径往往相互协作才能发挥作用。通路之间相互作用的变化与细胞特性和功能的变化密切相关，因此与表型的变化密切相关。因此，与特定表型相对应的途径相互作用，特别是其随时间的变化，对于了解细胞功能和表型可塑性是至关重要的。方法根据预先定义的途径和结合蛋白质-蛋白质相互作用(PPI)数据，我们计算每对不同途径对应的基因集之间的PPI，以构建一个全面的途径网络。然后，我们提出了一个新的概念--特征子通路网络(CSPN)来实现表型特异性通路的相互作用。通过添加与特定表型、血管生成相关的基因表达数据，得出了分别对应于白细胞介素1(IL-1)和肿瘤坏死因子α(肿瘤坏死因子α)刺激人脐静脉内皮细胞(HUVECs)的活性PPI。结果构建了一个包含37条信号通路和263条通路相互作用的综合通路网络。两个表型特异性的血管生成CSPN，分别对应于IL-1和肿瘤坏死因子-α刺激血管内皮细胞。根据表型特异性CSPN，分别检测到涉及B细胞受体、T细胞受体、Toll样受体、丝裂原活化蛋白激酶、血管内皮生长因子和ErbB信号通路相互作用的静态CSPN和涉及转化生长因子-β、Wnt、p53信号通路和细胞周期通路相互作用的动态CSPN，它们分别涉及IL-1和肿瘤坏死因子-α刺激人脐静脉内皮细胞的血管生成。我们推测，在某些情况下，静态的CSPN维持着细胞的相关基本功能，而动态的CSPN则体现了细胞对刺激的可塑性反应，从而反映了细胞的表型可塑性。此外，本工作中发现的两种潜在的CSPN，静态CSPN和动态CSPN，有助于深入了解HUVEC的特定功能及其在血管生成中的表型可塑性。
BackgroundPathways in biological system often cooperate with each other to function. Changes of interactions among pathways tightly associate with alterations in the properties and functions of the cell and hence alterations in the phenotype. So, the pathway interactions and especially their changes over time corresponding to specific phenotype are critical to understanding cell functions and phenotypic plasticity.MethodsWith prior-defined pathways and incorporated protein-protein interaction (PPI) data, we counted PPIs between corresponding gene sets of each pair of distinct pathways to construct a comprehensive pathway network. Then we proposed a novel concept, characteristic sub pathway network (CSPN), to realize the phenotype-specific pathway interactions. By adding gene expression data regarding a given phenotype, angiogenesis, active PPIs corresponding to stimulation of interleukin-1 (IL-1) and tumor necrosis factor α (TNF-α) on human umbilical vein endothelial cells (HUVECs) respectively were derived. Two kinds of CSPN, namely the static or the dynamic CSPN, were detected by counting active PPIs.ResultsA comprehensive pathway network containing 37 signalling pathways as nodes and 263 pathway interactions were obtained. Two phenotype-specific CSPNs for angiogenesis, corresponding to stimulation of IL-1 and TNF-α on HUVEC respectively, were addressed. From phenotype-specific CSPNs, a static CSPN involving interactions among B cell receptor, T cell receptor, Toll-like receptor, MAPK, VEGF, and ErbB signalling pathways, and a dynamic CSPN involving interactions among TGF-β, Wnt, p53 signalling pathways and cell cycle pathway, were detected for angiogenesis on HUVEC after stimulation of IL-1 and TNF-α respectively. We inferred that, in certain case, the static CSPN maintains related basic functions of the cells, whereas the dynamic CSPN manifests the cells' plastic responses to stimulus and therefore reflects the cells' phenotypic plasticity.ConclusionThe comprehensive pathway network helps us realize the cooperative behaviours among pathways. Moreover, two kinds of potential CSPNs found in this work, the static CSPN and the dynamic CSPN, are helpful to deeply understand the specific function of HUVEC and its phenotypic plasticity in regard to angiogenesis.