Identification of Essential Proteins Based on Edge Clustering Coefficient

Identification of essential proteins is key to understanding the minimal requirements for cellular life and important for drug design. The rapid increase of available protein-protein interaction (PPI) data has made it possible to detect protein essentiality on network level. A series of centrality measures have been proposed to discover essential proteins based on network topology. However, most of them tended to focus only on the location of single protein, but ignored the relevance between interactions and protein essentiality. In this paper, a new centrality measure for identifying essential proteins based on edge clustering coefficient, named as NC, is proposed. Different from previous centrality measures, NC considers both the centrality of a node and the relationship between it and its neighbors. For each interaction in the network, we calculate its edge clustering coefficient. A node's essentiality is determined by the sum of the edge clustering coefficients of interactions connecting it and its neighbors. The new centrality measure NC takes into account the modular nature of protein essentiality. NC is applied to three different types of yeast protein-protein interaction networks, which are obtained from the DIP database, the MIPS database and the BioGRID database, respectively. The experimental results on the three different networks show that the number of essential proteins discovered by NC universally exceeds that discovered by the six other centrality measures: DC, BC, CC, SC, EC, and IC. Moreover, the essential proteins discovered by NC show significant cluster effect.

[1]  P. Shannon,et al.  Cytoscape: a software environment for integrated models of biomolecular interaction networks. , 2003, Genome research.

[2]  Terry Roemer,et al.  Essential Gene Identification and Drug Target Prioritization in Aspergillus fumigatus , 2007, PLoS pathogens.

[3]  A. Barabasi,et al.  Lethality and centrality in protein networks , 2001, Nature.

[4]  L. Freeman Centrality in social networks conceptual clarification , 1978 .

[5]  Dmitrij Frishman,et al.  MIPS: analysis and annotation of proteins from whole genomes in 2005 , 2006, Nucleic Acids Res..

[6]  A. Barabasi,et al.  Network biology: understanding the cell's functional organization , 2004, Nature Reviews Genetics.

[7]  Ney Lemke,et al.  Towards the prediction of essential genes by integration of network topology, cellular localization and biological process information , 2009, BMC Bioinformatics.

[8]  Ioannis Xenarios,et al.  DIP: the Database of Interacting Proteins , 2000, Nucleic Acids Res..

[9]  David Botstein,et al.  SGD: Saccharomyces Genome Database , 1998, Nucleic Acids Res..

[10]  Dirk Koschützki,et al.  How to identify essential genes from molecular networks? , 2009, BMC Systems Biology.

[11]  Insuk Lee,et al.  A high-accuracy consensus map of yeast protein complexes reveals modular nature of gene essentiality , 2007, BMC Bioinformatics.

[12]  Gary D Bader,et al.  Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry , 2002, Nature.

[13]  M E J Newman,et al.  Community structure in social and biological networks , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[14]  Yi Pan,et al.  A Fast Hierarchical Clustering Algorithm for Functional Modules Discovery in Protein Interaction Networks , 2011, IEEE/ACM Transactions on Computational Biology and Bioinformatics.

[15]  Yi Pan,et al.  Essential Proteins Discovery from Weighted Protein Interaction Networks , 2010, ISBRA.

[16]  Benjamin Audit,et al.  An exponential core in the heart of the yeast protein interaction network. , 2005, Molecular biology and evolution.

[17]  Dianne P. O'Leary,et al.  Why Do Hubs in the Yeast Protein Interaction Network Tend To Be Essential: Reexamining the Connection between the Network Topology and Essentiality , 2008, PLoS Comput. Biol..

[18]  Ernesto Estrada Virtual identification of essential proteins within the protein interaction network of yeast , 2005, Proteomics.

[19]  Claudio Castellano,et al.  Defining and identifying communities in networks. , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[20]  Huanye Sheng,et al.  Understanding gene essentiality by finely characterizing hubs in the yeast protein interaction network. , 2010, Biochemical and biophysical research communications.

[21]  Jianzhi Zhang,et al.  Why Do Hubs Tend to Be Essential in Protein Networks? , 2006, PLoS genetics.

[22]  Christie S. Chang,et al.  The BioGRID interaction database: 2013 update , 2012, Nucleic Acids Res..

[23]  Matthew W. Hahn,et al.  Comparative genomics of centrality and essentiality in three eukaryotic protein-interaction networks. , 2005, Molecular biology and evolution.

[24]  G. Arndt,et al.  Genome‐wide screening for gene function using RNAi in mammalian cells , 2005, Immunology and cell biology.

[25]  J. A. Rodríguez-Velázquez,et al.  Subgraph centrality in complex networks. , 2005, Physical review. E, Statistical, nonlinear, and soft matter physics.

[26]  B. Snel,et al.  Comparative assessment of large-scale data sets of protein–protein interactions , 2002, Nature.

[27]  Wen-Hsiung Li,et al.  Gene essentiality, gene duplicability and protein connectivity in human and mouse. , 2007, Trends in genetics : TIG.

[28]  Alpan Raval,et al.  Identifying Hubs in Protein Interaction Networks , 2009, PloS one.

[29]  P. Bonacich Power and Centrality: A Family of Measures , 1987, American Journal of Sociology.

[30]  K. Sneppen,et al.  Specificity and Stability in Topology of Protein Networks , 2002, Science.

[31]  Hon Wai Leong,et al.  Examination of the relationship between essential genes in PPI network and hub proteins in reverse nearest neighbor topology , 2010, BMC Bioinformatics.

[32]  R. Ozawa,et al.  A comprehensive two-hybrid analysis to explore the yeast protein interactome , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[33]  Dmitrij Frishman,et al.  MIPS: analysis and annotation of proteins from whole genomes in 2005 , 2005, Nucleic Acids Res..

[34]  M. Zelen,et al.  Rethinking centrality: Methods and examples☆ , 1989 .

[35]  Keunwan Park,et al.  Localized network centrality and essentiality in the yeast–protein interaction network , 2009, Proteomics.

[36]  Ronald W. Davis,et al.  Functional characterization of the S. cerevisiae genome by gene deletion and parallel analysis. , 1999, Science.

[37]  Yan Lin,et al.  DEG 5.0, a database of essential genes in both prokaryotes and eukaryotes , 2008, Nucleic Acids Res..

[38]  Leonard M. Freeman,et al.  A set of measures of centrality based upon betweenness , 1977 .

[39]  Hsuan-Cheng Huang,et al.  Essential core of protein-protein interaction network in Escherichia coli. , 2009, Journal of proteome research.

[40]  P. Bork,et al.  Functional organization of the yeast proteome by systematic analysis of protein complexes , 2002, Nature.

[41]  Alexander Rives,et al.  Modular organization of cellular networks , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[42]  D. Ingber,et al.  High-Betweenness Proteins in the Yeast Protein Interaction Network , 2005, Journal of biomedicine & biotechnology.

[43]  H. Bussey,et al.  Large‐scale essential gene identification in Candida albicans and applications to antifungal drug discovery , 2003, Molecular microbiology.

[44]  P. Stadler,et al.  Centers of complex networks. , 2003, Journal of theoretical biology.

[45]  Guillermo Owen,et al.  Centrality and power in social networks: a game theoretic approach , 2003, Math. Soc. Sci..

[46]  Kara Dolinski,et al.  The BioGRID Interaction Database: 2011 update , 2010, Nucleic Acids Res..

[47]  Taesung Park,et al.  Analysis of human disease genes in the context of gene essentiality. , 2008, Genomics.

[48]  O Mason,et al.  Graph theory and networks in Biology. , 2006, IET systems biology.

[49]  Ronald W. Davis,et al.  Functional profiling of the Saccharomyces cerevisiae genome , 2002, Nature.

[50]  Sanjay Kumar,et al.  Computational prediction of essential genes in an unculturable endosymbiotic bacterium, Wolbachia of Brugia malayi , 2009, BMC Microbiology.

[51]  James R. Knight,et al.  A comprehensive analysis of protein–protein interactions in Saccharomyces cerevisiae , 2000, Nature.