Formulating genome-scale kinetic models in the post-genome era.

Formulating genome-scale kinetic models in the post-genome era.
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在基因组后时代制定基因组规模的动力学模型。

DOI:
10.1038/msb.2008.8
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发表时间:
2008
影响因子:
9.9
通讯作者:
Palsson, Bernhard O.
Palsson, Bernhard O.
中科院分区:
生物学1区
文献类型:
--
作者:
Jamshidi, Neema;Palsson, Bernhard O.

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生物界现在充斥着高通量数据集,并正在努力应对整合不同数据集的挑战。这种整合采取的形式是对大型数据集进行统计分析,或通过自下而上的反应网络重建。虽然已经取得了进展,统计和结构的方法,大规模的系统仍然难用传统的方法建立动态模型。注释基因组的可用性使得能够重建基因组规模的网络,现在高通量代谢组学和通量组学数据沿着热力学信息的可用性为建立基因组规模的动力学模型提供了可能性。我们在这里描述了一个框架,用于构建和分析这样的模型。数学分析的挑战反映在四个基本属性中,(i)雅可比矩阵分解为化学,动力学和热力学信息,(ii)化学计量矩阵和梯度矩阵转置之间的结构相似性,(iii)使通量或浓度能够作为自变量的对偶变换,以及(iv)生物网络中的时标层次。这些特性的识别和评价突出了值得注意的和具有挑战性的新的计算机分析问题。
The biological community is now awash in high-throughput data sets and is grappling with the challenge of integrating disparate data sets. Such integration has taken the form of statistical analysis of large data sets, or through the bottom–up reconstruction of reaction networks. While progress has been made with statistical and structural methods, large-scale systems have remained refractory to dynamic model building by traditional approaches. The availability of annotated genomes enabled the reconstruction of genome-scale networks, and now the availability of high-throughput metabolomic and fluxomic data along with thermodynamic information opens the possibility to build genome-scale kinetic models. We describe here a framework for building and analyzing such models. The mathematical analysis challenges are reflected in four foundational properties, (i) the decomposition of the Jacobian matrix into chemical, kinetic and thermodynamic information, (ii) the structural similarity between the stoichiometric matrix and the transpose of the gradient matrix, (iii) the duality transformations enabling either fluxes or concentrations to serve as the independent variables and (iv) the timescale hierarchy in biological networks. Recognition and appreciation of these properties highlight notable and challenging new in silico analysis issues.
DOI: 10.1186/1752-0509-1-26
发表时间: 2007-06-08
影响因子: --
作者:
Jamshidi, Neema;Palsson, Bernhard O
通讯作者: Palsson, Bernhard O
DOI: 10.1529/biophysj.104.050385
发表时间: 2005-03-01
影响因子: 3.4
作者:
Famili, I;Mahadevan, R;Palsson, BO
通讯作者: Palsson, BO
DOI: 10.1038/msb4100155
发表时间: 2007
影响因子: 9.9
作者:
通讯作者: --
DOI: 10.1073/pnas.0609508103
发表时间: 2006-12-19
影响因子: 11.1
作者:
Brauer, Matthew J.;Yuan, Jie;Rabinowitz, Joshua D.
通讯作者: Rabinowitz, Joshua D.
DOI: 10.1038/ng1432
发表时间: 2004-10-01
期刊: NATURE GENETICS
影响因子: 30.8
作者:
Fong, SS;Palsson, BO
通讯作者: Palsson, BO