Nutrigenomics Research Group, UCD Conway Institute, University College Dublin, Ireland.
PLoS Comput Biol. 2011 Nov;7(11):e1002223. doi: 10.1371/journal.pcbi.1002223. Epub 2011 Nov 3.
Understanding the molecular link between diet and health is a key goal in nutritional systems biology. As an alternative to pathway analysis, we have developed a joint multivariate and network-based approach to analysis of a dataset of habitual dietary records, adipose tissue transcriptomics and comprehensive plasma marker profiles from human volunteers with the Metabolic Syndrome. With this approach we identified prominent co-expressed sub-networks in the global metabolic network, which showed correlated expression with habitual n-3 PUFA intake and urinary levels of the oxidative stress marker 8-iso-PGF(2α). These sub-networks illustrated inherent cross-talk between distinct metabolic pathways, such as between triglyceride metabolism and production of lipid signalling molecules. In a parallel promoter analysis, we identified several adipogenic transcription factors as potential transcriptional regulators associated with habitual n-3 PUFA intake. Our results illustrate advantages of network-based analysis, and generate novel hypotheses on the transcriptomic link between habitual n-3 PUFA intake, adipose tissue function and oxidative stress.
理解饮食与健康之间的分子联系是营养系统生物学的一个关键目标。作为途径分析的替代方法，我们开发了一种联合多变量和基于网络的方法，用于分析一组习惯性饮食记录、人体志愿者脂肪组织转录组学和综合血浆标志物图谱以及代谢综合征的数据集。通过这种方法，我们在全球代谢网络中确定了突出的共表达子网络，这些网络与习惯性 n-3PUFA 摄入和氧化应激标志物 8-iso-PGF(2α)的尿水平呈相关表达。这些子网络说明了不同代谢途径之间固有的交叉对话，例如甘油三酯代谢和脂质信号分子的产生之间。在平行启动子分析中，我们确定了几个脂肪形成转录因子作为与习惯性 n-3PUFA 摄入相关的潜在转录调节因子。我们的结果说明了基于网络的分析的优势，并生成了关于习惯性 n-3PUFA 摄入、脂肪组织功能和氧化应激之间转录组联系的新假设。
