Saccenti Edoardo, Suarez-Diez Maria, Luchinat Claudio, Santucci Claudio, Tenori Leonardo
Laboratory of Systems and Synthetic Biology, Wageningen University and Research Center , Dreijenplein 10, 6703 HB Wageningen, The Netherlands.
J Proteome Res. 2015 Feb 6;14(2):1101-11. doi: 10.1021/pr501075r. Epub 2014 Dec 8.
The complex nature of the mechanisms behind cardiovascular diseases prevents the detection of latent early risk conditions. Network representations are ideally suited to investigate the complex interconnections between the individual components of a biological system that underlies complex diseases. Here, we investigate the patterns of correlations of an array of 29 metabolites identified and quantified in the plasma of 864 healthy blood donors and use a systems biology approach to define metabolite probabilistic networks specific for low and high latent cardiovascular risk. We adapted methods based on the likelihood of correlation and methods from information theory and combined them with resampling techniques. Our results show that plasma metabolite networks can be defined that associate with latent cardiovascular disease risk. The analysis of the networks supports our previous finding of a possible association between cardiovascular risk and impaired mitochondrial activity and highlights post-translational modifications (glycosilation and oxidation) of lipoproteins as a possible target-mechanism for early detection of latent cardiovascular risk.
心血管疾病背后机制的复杂性使得潜在的早期风险状况难以被检测出来。网络表示法非常适合用于研究构成复杂疾病基础的生物系统各个组成部分之间的复杂相互联系。在此,我们研究了在864名健康献血者血浆中鉴定并定量的29种代谢物的相关模式,并采用系统生物学方法来定义针对低和高潜在心血管风险的代谢物概率网络。我们采用了基于相关性可能性的方法以及信息论方法,并将它们与重采样技术相结合。我们的结果表明,可以定义与潜在心血管疾病风险相关的血浆代谢物网络。对这些网络的分析支持了我们之前关于心血管风险与线粒体活性受损之间可能存在关联的发现,并突出了脂蛋白的翻译后修饰(糖基化和氧化)作为早期检测潜在心血管风险的一种可能的靶向机制。