Global functional atlas of Escherichia coli encompassing previously uncharacterized proteins.
Global functional atlas of Escherichia coli encompassing previously uncharacterized proteins.
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DOI：
10.1371/journal.pbio.1000096
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发表时间：
2009-04-28
期刊：
影响因子：
9.8
通讯作者：
Emili A
中科院分区：
文献类型：
--
作者：
Hu P;Janga SC;Babu M;Díaz-Mejía JJ;Butland G;Yang W;Pogoutse O;Guo X;Phanse S;Wong P;Chandran S;Christopoulos C;Nazarians-Armavil A;Nasseri NK;Musso G;Ali M;Nazemof N;Eroukova V;Golshani A;Paccanaro A;Greenblatt JF;Moreno-Hagelsieb G;Emili A
大肠杆菌K-12的4,225个蛋白质编码基因中有三分之一在功能上未被注释（孤儿）。许多细菌可以追溯到遥远的分支，如古细菌，这表明它们参与了基本的原核生物特征，而其他细菌似乎仅限于大肠杆菌，包括致病菌株。为了阐明孤儿的生物学作用，我们使用亲和标记的大肠杆菌菌株进行了广泛的蛋白质组学调查，并产生了全面的基因组背景推断，得出了几乎整个蛋白质组的高可信度概要，其中包括5,993种假定的物理相互作用和74,776种假定的功能关联，其中大多数是新的。各自概率网络的聚类揭示了离散多蛋白复合物和功能模块以及带注释的基因产物中假定的孤儿成员，而基于网络集成的机器学习策略则涉及特定生物过程中的孤儿。我们提供了额外的实验证据，支持孤儿参与蛋白质合成、氨基酸代谢、生物膜形成、运动和细菌包膜组装。该资源提供了一种模式微生物的“全系统”功能蓝图，并深入了解了以前未表征的蛋白质的生物学和进化意义。现代生物学的一个目标是绘制通过直接和间接相互作用共同作用的生物过程的蛋白质组。这样的分组有时被称为功能模块。模块内蛋白质相互作用的类型包括产生蛋白质复合物的物理相互作用和构成代谢途径的生化关联。我们结合了蛋白质组学和生物信息学工具，并利用它们高可信度地破译了大量蛋白质相互作用，复合物和功能模块。此外，通过探索相互作用网络的拓扑结构，我们成功地预测了一些功能未知的蛋白质的特定生物学作用，并确定了一些潜在的药物靶点。虽然我们的工作主要集中在大肠杆菌上，但我们的系统发育预测表明，我们的观察和预测的相当一部分可以外推到许多其他细菌分类群。由于从这项研究中获得的所有数据都是公开的，其他人可能会在我们的工作基础上进一步进行假设驱动的基因功能发现研究。一种整合蛋白质组学和基因组上下文工具的新资源提供了e的“系统范围”功能蓝图。大肠杆菌，深入了解以前未表征的蛋白质的生物学和进化意义。
One-third of the 4,225 protein-coding genes of Escherichia coli K-12 remain functionally unannotated (orphans). Many map to distant clades such as Archaea, suggesting involvement in basic prokaryotic traits, whereas others appear restricted to E. coli, including pathogenic strains. To elucidate the orphans' biological roles, we performed an extensive proteomic survey using affinity-tagged E. coli strains and generated comprehensive genomic context inferences to derive a high-confidence compendium for virtually the entire proteome consisting of 5,993 putative physical interactions and 74,776 putative functional associations, most of which are novel. Clustering of the respective probabilistic networks revealed putative orphan membership in discrete multiprotein complexes and functional modules together with annotated gene products, whereas a machine-learning strategy based on network integration implicated the orphans in specific biological processes. We provide additional experimental evidence supporting orphan participation in protein synthesis, amino acid metabolism, biofilm formation, motility, and assembly of the bacterial cell envelope. This resource provides a “systems-wide” functional blueprint of a model microbe, with insights into the biological and evolutionary significance of previously uncharacterized proteins. One goal of modern biology is to chart groups of proteins that act together to perform biological processes via direct and indirect interactions. Such groupings are sometimes called functional modules. The types of protein interactions within modules include physical interactions that generate protein complexes and biochemical associations that make up metabolic pathways. We have combined proteomic and bioinformatic tools, and used them to decipher a large number of protein interactions, complexes, and functional modules with high confidence. In addition, exploring the topology of the resulting interaction networks, we successfully predicted specific biological roles for a number of proteins with previously unknown functions, and identified some potential drug targets. Although our work is focused on E. coli, our phylogenetic projections suggest that a considerable fraction of our observations and predictions can be extrapolated to many other bacterial taxa. As all the data derived from this study are publicly available, others may build on our work for further hypothesis-driven studies of gene function discovery. A novel resource integrating proteomic and genome context-based tools provides a "systems-wide" functional blueprint ofE. coli, with insights into the biological and evolutionary significance of previously uncharacterized proteins.
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影响因子：
14.9
作者：
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Bork, P