Examination of the relationship between essential genes in PPI network and hub proteins in reverse nearest neighbor topology

BMC Bioinformatics

Research Article

Sriganesh Srihari¹  Hoong Kee Ng¹  Hon Wai Leong¹  Kang Ning²  Alexey I Nesvizhskii³ 

[1] Department of Computer Science, National University of Singapore, 117417, Singapore;Department of Pathology, University of Michigan, 4237 Medical Science Building I, 48109, Ann Arbor, MI, USA;Department of Pathology, University of Michigan, 4237 Medical Science Building I, 48109, Ann Arbor, MI, USA;Center for Computational Biology and Medicine, University of Michigan, 48109, Ann Arbor, MI, USA;

关键词: Gene Ontology;    Cluster Centrality;    Essential Gene;    Weighted Directed Graph;    Reverse Nearest Neighbor;   

DOI  :  10.1186/1471-2105-11-505

 received in 2010-01-29, accepted in 2010-10-12,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundIn 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).ResultsThe 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.ConclusionsThis 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.

【 授权许可】

Unknown   
© Ning et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.