Global relative parameter sensitivities of the feed-forward loops in genetic networks

Global relative parameter sensitivities of the feed-forward loops in genetic networks
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遗传网络中前馈回路的全局相对参数灵敏度

DOI:
10.1016/j.neucom.2011.05.034
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发表时间:
2012-02
期刊:
影响因子:
6
通讯作者:
M. J. Ogorzalek
M. J. Ogorzalek
中科院分区:
计算机科学2区
文献类型:
--
作者:
P. Wang;J. Lü;M. J. Ogorzalek

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众所周知,前馈回路(FFL)是真实的生物网络中的典型网络模体。在过去的十年中,FFL的结构、功能以及噪声特性受到越来越多的关注。通过引入一种简单的新方法,进一步研究了Hill动力学模型遗传网络中FFL的全局相对参数灵敏度(GRPS)。我们的研究结果表明:(i)对于相干FFL(CFFL),最丰富的类型1配置(C1)对系统参数全局最敏感,而对于非相干FFL(IFFL),最丰富的类型1配置(I1)对系统参数全局最不敏感;(ii)FFL配置的噪声越小,该电路对其参数的全局越敏感;以及(iii)最丰富的FFL配置通常是对系统参数变化(IFFL)最不敏感(鲁棒性)的或噪声最小的(CFFL)。因此,上述结果可以很好地解释为什么FFL是网络模体,并在进化中被自然选择。此外,建议GRPS方法揭示了一些潜在的真实的世界的应用,如合成的遗传电路,预测干预措施在医学和生物技术的效果,等等。
It is well known that the feed-forward loops (FFLs) are typical network motifs in many real world biological networks. The structures, functions, as well as noise characteristics of FFLs have received increasing attention over the last decade. This paper aims to further investigate the global relative parameter sensitivities (GRPS) of FFLs in genetic networks modeled by Hill kinetics by introducing a simple novel approach. Our results indicate that: (i) for the coherent FFLs (CFFLs), the most abundant type 1 configuration (C1) is the most globally sensitive to system parameters, while for the incoherent FFLs (IFFLs), the most abundant type 1 configuration (I1) is the least globally sensitive to system parameters; (ii) the less noisy of a FFL configuration, the more globally sensitive of this circuit to its parameters; and (iii) the most abundant FFL configurations are often either the least sensitive (robust) to system parameters variation (IFFLs) or the least noisy (CFFLs). Therefore, the above results can well explain the reason why FFLs are network motifs and are selected by nature in evolution. Furthermore, the proposed GRPS approach sheds some light on the potential real world applications, such as the synthetic genetic circuits, predicting the effect of interventions in medicine and biotechnology, and so on.
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