Beebe Kirk, Kennedy Adam D
Metabolon Inc., Durham, NC, USA.
Comput Struct Biotechnol J. 2016 Jan 21;14:97-105. doi: 10.1016/j.csbj.2016.01.001. eCollection 2016.
Precision medicine is an active component of medical practice today, but aspirations are to both broaden its reach to a greater diversity of individuals and improve its "precision" by enhancing the ability to define even more disease states in combination with associated treatments. Given complexity of human phenotypes, much work is required. In this review, we deconstruct this challenge at a high level to define what is needed to move closer toward these aspirations. In the context of the variables that influence the diverse array of phenotypes across human health and disease - genetics, epigenetics, environmental influences, and the microbiome - we detail the factors behind why an individual's biochemical (metabolite) composition is increasingly regarded as a key element to precisely defining phenotypes. Although an individual's biochemical (metabolite) composition is generally regarded, and frequently shown, to be a surrogate to the phenotypic state, we review how metabolites (and therefore an individual's metabolic profile) are also functionally related to the myriad of phenotypic influencers like genetics and the microbiota. We describe how using the technology to comprehensively measure an individual's biochemical profile - metabolomics - is integrative to defining individual phenotypes and how it is currently being deployed in efforts to continue to elaborate on human health and disease in large population studies. Finally, we summarize instances where metabolomics is being used to assess individual health in instances where signatures (i.e. biomarkers) have been defined.
精准医学是当今医学实践的一个积极组成部分，但目标是扩大其覆盖范围，涵盖更多样化的个体，并通过增强结合相关治疗来定义更多疾病状态的能力来提高其“精准度”。鉴于人类表型的复杂性，仍有许多工作要做。在这篇综述中，我们从高层次剖析这一挑战，以确定为更接近这些目标需要做些什么。在影响人类健康和疾病中各种表型的变量——遗传学、表观遗传学、环境影响和微生物群——的背景下，我们详细阐述了为什么个体的生化（代谢物）组成越来越被视为精确定义表型的关键因素。尽管个体的生化（代谢物）组成通常被视为并经常被证明是表型状态的替代指标，但我们回顾了代谢物（以及个体的代谢谱）如何在功能上也与遗传学和微生物群等众多表型影响因素相关。我们描述了如何利用技术全面测量个体的生化谱——代谢组学——对于定义个体表型是不可或缺的，以及它目前如何在大型人群研究中用于继续阐述人类健康和疾病。最后，我们总结了在已定义特征（即生物标志物）的情况下代谢组学用于评估个体健康的实例。
