Understanding 'global' systems biology: Metabonomics and the continuum of metabolism
Understanding 'global' systems biology: Metabonomics and the continuum of metabolism
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DOI：
10.1038/nrd1157
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发表时间：
2003-08-01
影响因子：
120.1
通讯作者：
Wilson, ID
中科院分区：
文献类型：
--
作者：
Nicholson, JK;Wilson, ID
为了将基因组学知识有效地应用于药物发现，需要通过系统生物学方法建立遗传变异和疾病过程之间的机制联系。人类有数百种功能特化的细胞类型，它们与环境因素有差异地相互作用，以影响疾病的发展和调节药物的作用。代谢组学可以提供一种模拟这些相互作用的方法，但“内源性”代谢过程（编码在基因组中，内在的细胞功能）和“外源性”（外来化合物）代谢之间的关系知之甚少，特别是在环境因素方面。我们提出了一个概述的“全球”哺乳动物的代谢转换，应占在人类系统生物学模型，并提出了一种新的概率方法，以帮助了解基因疾病的关系和棘手的问题的特异质药物毒性。
To apply genomic knowledge effectively in drug discovery, mechanistic connectivities between genetic variation and disease processes need to be established via systems biology approaches. Humans have hundreds of functionally specialized cell types that interact differentially with environmental factors to influence disease development and to modulate the effects of drugs. Metabonomics can provide a means of modelling these interactions, but the relationships between 'endogenous' metabolic processes (coded in the genome and intrinsic to cellular function) and 'xenobiotic' (foreign compound) metabolism are poorly understood, especially with respect to environmental factors. We present an overview of 'global' mammalian metabolic conversions that should be accounted for in human systems biology models and propose a new probabilistic approach to help understand gene-disease relationships and vexed issues of idiosyncratic drug toxicity.