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

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]  M. DePamphilis,et al.  HUMAN DISEASE , 1957, The Ulster Medical Journal.

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

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

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

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

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

[7]  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.

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

[9]  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.

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

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

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

[13]  S. L. Wong,et al.  A Map of the Interactome Network of the Metazoan C. elegans , 2004, Science.

[14]  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.

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

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

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

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

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

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

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

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

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

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