Functional and Transcriptional Coherency of Modules in the Human Protein Interaction Network

Summary Modularity is a major design principle in interaction networks. Various studies have shown that protein interaction networks in prokaryotes and eukaryotes display a modular structure. A majority of the studies have been performed for the yeast interaction network, for which data have become abundant. The systematic examination of the human protein interaction network, however, is still in an early phase. To assess whether the human interaction network similarly displays a modular structure, we assembled a large protein network consisting of over 30,000 interactions. More than 670 modules were subsequently identified based on the detection of cliques. Inspection showed that these modules included numerous known protein complexes. The extracted modules were scrutinized for their coherency with respect to function, localization and expression, thereby allowing us to distinguish between stable and dynamic modules. Finally, the examination of the overlap between modules identified key proteins linking distinct molecular processes.

[1]  James R. Knight,et al.  A Protein Interaction Map of Drosophila melanogaster , 2003, Science.

[2]  A. Fraser,et al.  A first-draft human protein-interaction map , 2004, Genome Biology.

[3]  L. Mirny,et al.  Protein complexes and functional modules in molecular networks , 2003, Proceedings of the National Academy of Sciences of the United States of America.

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

[5]  H. Lehrach,et al.  A Human Protein-Protein Interaction Network: A Resource for Annotating the Proteome , 2005, Cell.

[6]  S. Batalov,et al.  A gene atlas of the mouse and human protein-encoding transcriptomes. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

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

[8]  A. Barabasi,et al.  The human disease network , 2007, Proceedings of the National Academy of Sciences.

[9]  Gary D Bader,et al.  BIND--The Biomolecular Interaction Network Database. , 2001, Nucleic acids research.

[10]  Erich E. Wanker,et al.  Comparison of Human Protein-Protein Interaction Maps , 2007, German Conference on Bioinformatics.

[11]  W. Wong,et al.  Transitive functional annotation by shortest-path analysis of gene expression data , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[12]  Pall I. Olason,et al.  A human phenome-interactome network of protein complexes implicated in genetic disorders , 2007, Nature Biotechnology.

[13]  Y. Benjamini,et al.  Controlling the false discovery rate: a practical and powerful approach to multiple testing , 1995 .

[14]  Illés J. Farkas,et al.  CFinder: locating cliques and overlapping modules in biological networks , 2006, Bioinform..

[15]  M. Ashburner,et al.  Gene Ontology: tool for the unification of biology , 2000, Nature Genetics.

[16]  Robert Hoffmann,et al.  HomoMINT: an inferred human network based on orthology mapping of protein interactions discovered in model organisms , 2005, BMC Bioinformatics.

[17]  Erich E. Wanker,et al.  UniHI: an entry gate to the human protein interactome , 2006, Nucleic Acids Res..

[18]  T. Vicsek,et al.  Uncovering the overlapping community structure of complex networks in nature and society , 2005, Nature.

[19]  S. L. Wong,et al.  Towards a proteome-scale map of the human protein–protein interaction network , 2005, Nature.

[20]  Erich E. Wanker,et al.  Flexible web-based integration of distributed large-scale human protein interaction maps , 2007, J. Integr. Bioinform..

[21]  Robert Gentleman,et al.  A graph-theoretic approach to testing associations between disparate sources of functional genomics data , 2004, Bioinform..

[22]  Igor Jurisica,et al.  Online Predicted Human Interaction Database , 2005, Bioinform..

[23]  Hanno Steen,et al.  Development of human protein reference database as an initial platform for approaching systems biology in humans. , 2003, Genome research.