Signaling network of lipids as a comprehensive scaffold for omics data integration in sputum of COPD patients
Signaling network of lipids as a comprehensive scaffold for omics data integration in sputum of COPD patients
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DOI：
10.1016/j.bbalip.2015.07.005
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发表时间：
2015-10-01
影响因子：
4.8
通讯作者：
Khodabandeh, Mahvash
中科院分区：
文献类型：
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作者：
Jamalkandi, Sadegh Azimzadeh;Mirzaie, Mehdi;Khodabandeh, Mahvash
慢性阻塞性肺疾病（COPD）是一种异质性和进行性炎症，与包括脂质生物合成在内的许多代谢途径的失调有关。脂质代谢如何影响COPD吸烟者的疾病进展尚不清楚。我们交叉检查了转录组学、蛋白质组学、代谢组学和表型组学的公开数据，以阐明COPD中脂质代谢紊乱的机制。我们重建了一个痰脂质COPD （SpLiCO）信号网络，利用活性/非活性和功能/功能失调的脂质介导信号通路来探索脂质代谢如何促进吸烟者COPD的发病机制。SpLiCO被进一步用于研究将COPD疾病严重程度和缺氧与鞘脂、脂肪酸和能量代谢中断联系起来的信号放大器、分布器、传播器、前馈和/或后馈回路。此外，分子依赖性的超图分析和计算确定了网络中具有模块化调节和信号分布活动的几个重要节点。我们基于系统的分析表明，花生四烯酸是COPD中神经鞘脂信号通路上调的关键早期信号分配者，而缺氧在对葡萄糖作为主要能量来源的依赖性升高中起关键作用。SpLiCo和临床数据的整合显示，在患有肺气肿、血管疾病、高血压和肺癌风险增加的吸烟者中，缺氧与鞘脂上调之间存在密切关联。(C) 2015 Elsevier B.V.版权所有
Chronic obstructive pulmonary disease (COPD) is a heterogeneous and progressive inflammatory condition that has been linked to the dysregulation of many metabolic pathways including lipid biosynthesis. How lipid metabolism could affect disease progression in smokers with COPD remains unclear. We cross-examined the transcriptomics, proteomics, metabolomics, and phenomics data available on the public domain to elucidate the mechanisms by which lipid metabolism is perturbed in COPD. We reconstructed a sputum lipid COPD (SpLiCO) signaling network utilizing active/inactive, and functional/dysfunctional lipid-mediated signaling pathways to explore how lipid-metabolism could promote COPD pathogenesis in smokers. SpLiCO was further utilized to investigate signal amplifiers, distributers, propagators, feed-forward and/or -back loops that link COPD disease severity and hypoxia to disruption in the metabolism of sphingolipids, fatty acids and energy. Also, hypergraph analysis and calculations for dependency of molecules identified several important nodes in the network with modular regulatory and signal distribution activities. Our systems-based analyses indicate that arachidonic acid is a critical and early signal distributer that is upregulated by the sphingolipid signaling pathway in COPD, while hypoxia plays a critical role in the elevated dependency to glucose as a major energy source. Integration of SpLiCo and clinical data shows a strong association between hypoxia and the upregulation of sphingolipids in smokers with emphysema, vascular disease, hypertension and those with increased risk of lung cancer. (C) 2015 Elsevier B.V. All rights reserved.