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酵母基因组规模代谢模型的进一步发展。

Further developments towards a genome-scale metabolic model of yeast.

作者信息

Dobson Paul D, Smallbone Kieran, Jameson Daniel, Simeonidis Evangelos, Lanthaler Karin, Pir Pınar, Lu Chuan, Swainston Neil, Dunn Warwick B, Fisher Paul, Hull Duncan, Brown Marie, Oshota Olusegun, Stanford Natalie J, Kell Douglas B, King Ross D, Oliver Stephen G, Stevens Robert D, Mendes Pedro

机构信息

School of Chemistry, The University of Manchester, Manchester M13 9PL, UK.

出版信息

BMC Syst Biol. 2010 Oct 28;4:145. doi: 10.1186/1752-0509-4-145.

DOI:10.1186/1752-0509-4-145
PMID:21029416
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2988745/
Abstract

BACKGROUND

To date, several genome-scale network reconstructions have been used to describe the metabolism of the yeast Saccharomyces cerevisiae, each differing in scope and content. The recent community-driven reconstruction, while rigorously evidenced and well annotated, under-represented metabolite transport, lipid metabolism and other pathways, and was not amenable to constraint-based analyses because of lack of pathway connectivity.

RESULTS

We have expanded the yeast network reconstruction to incorporate many new reactions from the literature and represented these in a well-annotated and standards-compliant manner. The new reconstruction comprises 1102 unique metabolic reactions involving 924 unique metabolites--significantly larger in scope than any previous reconstruction. The representation of lipid metabolism in particular has improved, with 234 out of 268 enzymes linked to lipid metabolism now present in at least one reaction. Connectivity is emphatically improved, with more than 90% of metabolites now reachable from the growth medium constituents. The present updates allow constraint-based analyses to be performed; viability predictions of single knockouts are comparable to results from in vivo experiments and to those of previous reconstructions.

CONCLUSIONS

We report the development of the most complete reconstruction of yeast metabolism to date that is based upon reliable literature evidence and richly annotated according to MIRIAM standards. The reconstruction is available in the Systems Biology Markup Language (SBML) and via a publicly accessible database http://www.comp-sys-bio.org/yeastnet/.

摘要

背景

迄今为止,已有多个基因组规模的网络重建用于描述酿酒酵母的代谢过程,每个重建在范围和内容上都有所不同。最近由社区驱动的重建虽然有充分的证据且注释完善,但在代谢物转运、脂质代谢和其他途径方面的呈现不足,并且由于缺乏途径连通性而不适用于基于约束的分析。

结果

我们扩展了酵母网络重建,纳入了文献中的许多新反应,并以注释完善且符合标准的方式呈现这些反应。新的重建包含1102个独特的代谢反应,涉及924种独特的代谢物——在范围上比以往任何重建都要大得多。特别是脂质代谢的呈现得到了改善,与脂质代谢相关的268种酶中有234种现在至少存在于一个反应中。连通性得到了显著改善,现在超过90%的代谢物可以从生长培养基成分中获得。目前的更新允许进行基于约束的分析;单基因敲除的生存能力预测与体内实验结果以及先前重建的结果相当。

结论

我们报告了迄今为止基于可靠文献证据并根据MIRIAM标准进行丰富注释的最完整的酵母代谢重建。该重建以系统生物学标记语言(SBML)提供,并可通过公开访问的数据库http://www.comp-sys-bio.org/yeastnet/获取。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5db/2988745/a6d2c7ac6d0b/1752-0509-4-145-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5db/2988745/c0c73524e0cb/1752-0509-4-145-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5db/2988745/7ac8c5a64b81/1752-0509-4-145-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5db/2988745/865efe59aae3/1752-0509-4-145-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5db/2988745/a6d2c7ac6d0b/1752-0509-4-145-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5db/2988745/c0c73524e0cb/1752-0509-4-145-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5db/2988745/7ac8c5a64b81/1752-0509-4-145-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5db/2988745/865efe59aae3/1752-0509-4-145-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5db/2988745/a6d2c7ac6d0b/1752-0509-4-145-4.jpg

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