Environmental and genetic perturbations reveal different networks of metabolic regulation
Environmental and genetic perturbations reveal different networks of metabolic regulation
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DOI：
10.1038/msb.2011.96
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发表时间：
2011-12-01
影响因子：
9.9
通讯作者：
Clark, Andrew G.
中科院分区：
文献类型：
--
作者：
Greenberg, Anthony J.;Hackett, Sean R.;Clark, Andrew G.
系统生物学的进步有赖于对生物网络的准确描述。调控网络中的连接被识别为跨越一系列环境或遗传扰动的基因表达的相关性。为了使用这些信息来预测系统行为，我们必须测试扰动的性质如何影响它们所揭示的网络拓扑。为了探讨这个问题，我们重点研究了果蝇的新陈代谢。我们的干扰来源是来自五个群体的92个野生衍生品系的一组杂交，复制的方式允许单独评估遗传变异和环境波动的影响。我们直接测定了酶的活性和代谢产物的水平。利用多元贝叶斯模型估计代谢参数之间的协方差，建立网络拓扑的细粒度概率模型。在五个种群中，环境和遗传共同调节网络基本上是相同的。然而，遗传和环境的扰动揭示了代谢调节的质量差异，这表明环境变化，如改变饮食，产生的系统效应与遗传变化不同，即使主要目标是相同的。《分子系统生物学》7：563；2011年12月20日在线出版；doi：10.1038/msb.2011.96
Progress in systems biology depends on accurate descriptions of biological networks. Connections in a regulatory network are identified as correlations of gene expression across a set of environmental or genetic perturbations. To use this information to predict system behavior, we must test how the nature of perturbations affects topologies of networks they reveal. To probe this question, we focused on metabolism of Drosophila melanogaster. Our source of perturbations is a set of crosses among 92 wild-derived lines from five populations, replicated in a manner permitting separate assessment of the effects of genetic variation and environmental fluctuation. We directly assayed activities of enzymes and levels of metabolites. Using a multivariate Bayesian model, we estimated covariance among metabolic parameters and built fine-grained probabilistic models of network topology. The environmental and genetic co-regulation networks are substantially the same among five populations. However, genetic and environmental perturbations reveal qualitative differences in metabolic regulation, suggesting that environmental shifts, such as diet modifications, produce different systemic effects than genetic changes, even if the primary targets are the same. Molecular Systems Biology 7: 563; published online 20 December 2011; doi: 10.1038/msb.2011.96