Examination of the relationship between essential genes in PPI network and hub proteins in reverse nearest neighbor topology.
Examination of the relationship between essential genes in PPI network and hub proteins in reverse nearest neighbor topology.
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DOI：
10.1186/1471-2105-11-505
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发表时间：
2010-10-12
影响因子：
3
通讯作者：
Nesvizhskii AI
中科院分区：
文献类型：
--
作者：
Ning K;Ng HK;Srihari S;Leong HW;Nesvizhskii AI
在许多蛋白质-蛋白质相互作用(PPI)网络中，紧密连接的HUB蛋白更有可能是必不可少的蛋白质。这被称为中心性-致命性规则，它表明蛋白质在PPI网络中的拓扑位置与其生物本质有关。虽然在许多PPI网络中都可以观察到这样的连接，但这些连接的基本拓扑属性还没有被清楚地理解。一些推测的连接是基本蛋白质参与整个网络连接的维持，或者它们在基本蛋白质簇中发挥作用。在这项工作中，我们试图通过确定蛋白质重要性和反向最近邻拓扑(RNN)的相关性，从不同的角度研究必要蛋白质的放置和网络拓扑。RNN拓扑是从PPI网络派生的加权有向图，它是PPI网络中蛋白质之间拓扑依赖的自然表示。与最初的PPI网络类似，我们观察到RNN拓扑中的必要蛋白往往是枢纽蛋白。此外，必需基因在RNN拓扑结构中包含许多HUB蛋白的簇(RNN蛋白簇)中丰富。基于RNN拓扑学中必需基因的这两个性质，我们提出了一种新的度量：RNN簇中心性。来自各种PPI网络的结果表明，在所选蛋白质是关键蛋白质的比例方面，RNN簇中心性优于其他中心性度量。我们还研究了RNN簇的生物学重要性。这项研究表明，RNN簇中心性提供了蛋白质重要性与蛋白质在PPI网络中的位置之间的最佳关联。此外，合并的RNN簇被发现在拓扑上具有重要意义，因为必需蛋白在RNN簇中显著丰富，并且由于它们在许多基因本体论(GO)过程中发挥重要作用而具有生物学意义。
In many protein-protein interaction (PPI) networks, densely connected hub proteins are more likely to be essential proteins. This is referred to as the "centrality-lethality rule", which indicates that the topological placement of a protein in PPI network is connected with its biological essentiality. Though such connections are observed in many PPI networks, the underlying topological properties for these connections are not yet clearly understood. Some suggested putative connections are the involvement of essential proteins in the maintenance of overall network connections, or that they play a role in essential protein clusters. In this work, we have attempted to examine the placement of essential proteins and the network topology from a different perspective by determining the correlation of protein essentiality and reverse nearest neighbor topology (RNN). The RNN topology is a weighted directed graph derived from PPI network, and it is a natural representation of the topological dependences between proteins within the PPI network. Similar to the original PPI network, we have observed that essential proteins tend to be hub proteins in RNN topology. Additionally, essential genes are enriched in clusters containing many hub proteins in RNN topology (RNN protein clusters). Based on these two properties of essential genes in RNN topology, we have proposed a new measure; the RNN cluster centrality. Results from a variety of PPI networks demonstrate that RNN cluster centrality outperforms other centrality measures with regard to the proportion of selected proteins that are essential proteins. We also investigated the biological importance of RNN clusters. This study reveals that RNN cluster centrality provides the best correlation of protein essentiality and placement of proteins in PPI network. Additionally, merged RNN clusters were found to be topologically important in that essential proteins are significantly enriched in RNN clusters, and biologically important because they play an important role in many Gene Ontology (GO) processes.
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影响因子：
4.3
作者：
Batada NN;Hurst LD;Tyers M
通讯作者：
Tyers M
影响因子：
9.8
作者：
Batada NN;Reguly T;Breitkreutz A;Boucher L;Breitkreutz BJ;Hurst LD;Tyers M
通讯作者：
Tyers M
影响因子：
64.8
作者：
Gavin, AC;Bösche, M;Superti-Furga, G
通讯作者：
Superti-Furga, G
影响因子：
64.8
作者：
Jeong, H;Mason, SP;Oltvai, ZN
通讯作者：
Oltvai, ZN
影响因子：
64.8
作者：
Gavin, AC;Aloy, P;Superti-Furga, G
通讯作者：
Superti-Furga, G