Compartmentalization of the Edinburgh Human Metabolic Network.
Compartmentalization of the Edinburgh Human Metabolic Network.
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爱丁堡人体代谢网络的划分
DOI：
10.1186/1471-2105-11-393
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发表时间：
2010-07-22
影响因子：
3
通讯作者：
Goryanin I
中科院分区：
文献类型：
--
作者：
Hao T;Ma HW;Zhao XM;Goryanin I
研究背景人体代谢的直接体内研究因各种亚细胞器的不同代谢功能而变得复杂。不同细胞器中的不同微环境可能导致相同蛋白质的不同功能以及相同代谢反应使用不同酶。为了更好地了解在人体代谢的复杂性，一个分区的人体代谢网络与集成的亚细胞位置informationsResultsWe扩展了以前重建的爱丁堡人体代谢网络（EHMN）[马，等人。分子系统生物学，3：135，2007]通过整合的亚细胞位置信息的反应，增加运输反应和完善的蛋白质反应的关系的基础上的位置信息。首先，从基因本体中获得蛋白质位置信息，并通过Swiss-Prot位置关键字搜索进行补充。然后根据蛋白质-反应关系将EHMN中的所有反应分配到一个位置，得到一个初步的划分网络。我们研究了每个途径中的局部子网络，通过连接性分析来识别间隙和孤立的反应，并根据文献中的信息改进了位置信息。结果，数百个反应的位置信息被修改，数百个不正确的蛋白质-反应关系被纠正。添加了超过1400个转运反应以连接位置特异性代谢网络。为了验证网络，我们进行了途径分析，以检查网络合成或降解某些关键代谢物的能力。与以前发表的人类代谢网络（Human Recon 1）相比，我们的网络包含超过1000个以上的反应分配到明确的cellularcompartment.ConclusionsBy结合蛋白质的位置信息，网络连接分析和手动文献检索，我们已经重建了一个更完整的划分的人类代谢网络。整个网络可在 http://www.ehmn.bioinformatics.ed.ac.uk 免费供学术使用。
BackgroundDirect in vivo investigation of human metabolism is complicated by the distinct metabolic functions of various sub-cellular organelles. Diverse micro-environments in different organelles may lead to distinct functions of the same protein and the use of different enzymes for the same metabolic reaction. To better understand the complexity in the human metabolism, a compartmentalized human metabolic network with integrated sub-cellular location information is required.ResultsWe extended the previously reconstructed Edinburgh Human Metabolic Network (EHMN) [Ma, et al. Molecular Systems Biology, 3:135, 2007] by integrating the sub-cellular location information for the reactions, adding transport reactions and refining the protein-reaction relationships based on the location information. Firstly, protein location information was obtained from Gene Ontology and complemented by a Swiss-Prot location keywords search. Then all the reactions in EHMN were assigned to a location based on the protein-reaction relationships to get a preliminary compartmentalized network. We investigated the localized sub-networks in each pathway to identify gaps and isolated reactions by connectivity analysis and refined the location information based on information from literature. As a result, location information for hundreds of reactions was revised and hundreds of incorrect protein-reaction relationships were corrected. Over 1400 transport reactions were added to link the location specific metabolic network. To validate the network, we have done pathway analysis to examine the capability of the network to synthesize or degrade certain key metabolites. Compared with a previously published human metabolic network (Human Recon 1), our network contains over 1000 more reactions assigned to clear cellular compartments.ConclusionsBy combining protein location information, network connectivity analysis and manual literature search, we have reconstructed a more complete compartmentalized human metabolic network. The whole network is available at http://www.ehmn.bioinformatics.ed.ac.uk and free for academic use.
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影响因子：
14.9
作者：
Ren Q;Chen K;Paulsen IT
通讯作者：
Paulsen IT
影响因子：
4.1
作者：
Dodt, G;Kim, DG;Mihalik, SJ
通讯作者：
Mihalik, SJ
影响因子：
4.1
作者：
Gómez-Fabre, PM;Aledo, JC;Márquez, J
通讯作者：
Márquez, J
影响因子：
7.4
作者：
Bode, K;Hooks, MA;Couée, I
通讯作者：
Couée, I
爱丁堡人类代谢网络重建及其功能分析。
影响因子：
9.9
作者：
Ma, Hongwu;Sorokin, Anatoly;Mazein, Alexander;Selkov, Alex;Selkov, Evgeni;Demin, Oleg;Goryanin, Igor
通讯作者：
Goryanin, Igor