The centrality of cancer proteins in human protein-protein interaction network: a revisit

Topological analysis of protein-protein interaction (PPI) networks has been widely applied to the investigation on cancer mechanisms. However, there is still a debate on whether cancer proteins exhibit more topological centrality compared to the other proteins in the human PPI network. To resolve this debate, we first identified four sets of human proteins, and then mapped these proteins into the yeast PPI network by homologous genes. Finally, we compared these proteins' properties in human and yeast PPI networks. Experiments over two real datasets demonstrated that cancer proteins tend to have higher degree and smaller clustering coefficient than non-cancer proteins. Experimental results also validated that cancer proteins have larger betweenness centrality compared to the other proteins on the STRING dataset. However, on the BioGRID dataset, the average betweenness centrality of cancer proteins is larger than that of disease and control proteins, but smaller than that of essential proteins.

[1]  Ulf Leser,et al.  A Comprehensive Benchmark of Kernel Methods to Extract Protein–Protein Interactions from Literature , 2010, PLoS Comput. Biol..

[2]  David Warde-Farley,et al.  Dynamic modularity in protein interaction networks predicts breast cancer outcome , 2009, Nature Biotechnology.

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

[4]  Igor Stagljar,et al.  Two-hybrid technologies in proteomics research. , 2008, Current opinion in biotechnology.

[5]  Zhongming Zhao,et al.  A comparative study of cancer proteins in the human protein-protein interaction network , 2010, BMC Genomics.

[6]  K. Gunsalus,et al.  Network modeling links breast cancer susceptibility and centrosome dysfunction. , 2007, Nature genetics.

[7]  Junfeng Xia,et al.  Do cancer proteins really interact strongly in the human protein-protein interaction network? , 2011, Comput. Biol. Chem..

[8]  R. Sharan,et al.  Protein networks in disease. , 2008, Genome research.

[9]  T. Hubbard,et al.  A census of human cancer genes , 2004, Nature Reviews Cancer.

[10]  Paul A. Bates,et al.  Global topological features of cancer proteins in the human interactome , 2006, Bioinform..

[11]  Tammy M. K. Cheng,et al.  Understanding cancer mechanisms through network dynamics. , 2012, Briefings in functional genomics.

[12]  Arun K. Ramani,et al.  How complete are current yeast and human protein-interaction networks? , 2006, Genome Biology.

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

[14]  H. Parkinson,et al.  A global map of human gene expression , 2010, Nature Biotechnology.

[15]  Peter D. Karp,et al.  A systematic study of genome context methods: calibration, normalization and combination , 2010, BMC Bioinformatics.