Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Mol Syst Biol. 2010 Dec 21;6:441. doi: 10.1038/msb.2010.93.
Comprehensive characterization of human tissues promises novel insights into the biological architecture of human diseases and traits. We assessed metabonomic, transcriptomic, and genomic variation for a large population-based cohort from the capital region of Finland. Network analyses identified a set of highly correlated genes, the lipid-leukocyte (LL) module, as having a prominent role in over 80 serum metabolites (of 134 measures quantified), including lipoprotein subclasses, lipids, and amino acids. Concurrent association with immune response markers suggested the LL module as a possible link between inflammation, metabolism, and adiposity. Further, genomic variation was used to generate a directed network and infer LL module's largely reactive nature to metabolites. Finally, gene co-expression in circulating leukocytes was shown to be dependent on serum metabolite concentrations, providing evidence for the hypothesis that the coherence of molecular networks themselves is conditional on environmental factors. These findings show the importance and opportunity of systematic molecular investigation of human population samples. To facilitate and encourage this investigation, the metabonomic, transcriptomic, and genomic data used in this study have been made available as a resource for the research community.
全面描述人体组织有望为人类疾病和特征的生物学结构提供新的见解。我们评估了来自芬兰首都地区的一个大型基于人群的队列的代谢组学、转录组学和基因组学变异。网络分析确定了一组高度相关的基因，即脂质-白细胞（LL）模块，作为超过 80 种血清代谢物（定量测量的 134 种中的一种）的主要作用因子，包括脂蛋白亚类、脂质和氨基酸。与免疫反应标志物的并发关联表明，LL 模块可能是炎症、代谢和肥胖之间的联系。此外，基因组变异被用来生成一个有向网络，并推断 LL 模块对代谢物的反应性。最后，循环白细胞中的基因共表达依赖于血清代谢物浓度，为分子网络本身的一致性取决于环境因素的假设提供了证据。这些发现表明了对人类人群样本进行系统分子研究的重要性和机会。为了促进和鼓励这种研究，本研究中使用的代谢组学、转录组学和基因组学数据已作为研究社区的资源提供。
