HomoMINT: an inferred human network based on orthology mapping of protein interactions discovered in model organisms

BackgroundThe application of high throughput approaches to the identification of protein interactions has offered for the first time a glimpse of the global interactome of some model organisms. Until now, however, such genome-wide approaches have not been applied to the human proteome.ResultsIn order to fill this gap we have assembled an inferred human protein interaction network where interactions discovered in model organisms are mapped onto the corresponding human orthologs. In addition to a stringent assignment to orthology classes based on the InParanoid algorithm, we have implemented a string matching algorithm to filter out orthology assignments of proteins whose global domain organization is not conserved. Finally, we have assessed the accuracy of our own, and related, inferred networks by benchmarking them against i) an assembled experimental interactome, ii) a network derived by mining of the scientific literature and iii) by measuring the enrichment of interacting protein pairs sharing common Gene Ontology annotation.ConclusionThe resulting networks are named HomoMINT and HomoMINT_filtered, the latter being based on the orthology table filtered by the domain architecture matching algorithm. They contains 9749 and 5203 interactions respectively and can be analyzed and viewed in the context of the experimentally verified interactions between human proteins stored in the MINT database. HomoMINT is constantly updated to take into account the growing information in the MINT database.

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

[2]  B. Séraphin,et al.  A generic protein purification method for protein complex characterization and proteome exploration , 1999, Nature Biotechnology.

[3]  G. Sumara,et al.  A Probabilistic Functional Network of Yeast Genes , 2004 .

[4]  Peer Bork,et al.  SMART 4.0: towards genomic data integration , 2004, Nucleic Acids Res..

[5]  Martin Vingron,et al.  IntAct: an open source molecular interaction database , 2004, Nucleic Acids Res..

[6]  Poethig Rs,et al.  Life with 25,000 genes. , 2001 .

[7]  C. Sander,et al.  The HUPO PSI's Molecular Interaction format—a community standard for the representation of protein interaction data , 2004, Nature Biotechnology.

[8]  Gary D Bader,et al.  Analyzing yeast protein–protein interaction data obtained from different sources , 2002, Nature Biotechnology.

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

[10]  Kimberly Van Auken,et al.  WormBase: a multi-species resource for nematode biology and genomics , 2004, Nucleic Acids Res..

[11]  R. Chanet,et al.  Protein interaction mapping: a Drosophila case study. , 2005, Genome research.

[12]  Ian M. Donaldson,et al.  BIND: the Biomolecular Interaction Network Database , 2001, Nucleic Acids Res..

[13]  Matteo Pellegrini,et al.  Prolinks: a database of protein functional linkages derived from coevolution , 2004, Genome Biology.

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

[15]  Lincoln Stein,et al.  Reactome: a knowledgebase of biological pathways , 2004, Nucleic Acids Res..

[16]  Luisa Montecchi Palazzi,et al.  Comparative interactomics , 2005, FEBS letters.

[17]  Dan Gusfield,et al.  Algorithms on Strings, Trees, and Sequences - Computer Science and Computational Biology , 1997 .

[18]  A. Valencia,et al.  A gene network for navigating the literature , 2004, Nature Genetics.

[19]  Christian E. V. Storm,et al.  Automatic clustering of orthologs and in-paralogs from pairwise species comparisons. , 2001, Journal of molecular biology.

[20]  Amos Bairoch,et al.  The ENZYME database in 2000 , 2000, Nucleic Acids Res..

[21]  Jean YH Yang,et al.  Bioconductor: open software development for computational biology and bioinformatics , 2004, Genome Biology.

[22]  Ioannis Xenarios,et al.  DIP, the Database of Interacting Proteins: a research tool for studying cellular networks of protein interactions , 2002, Nucleic Acids Res..

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

[24]  C. Chothia,et al.  Structure, function and evolution of multidomain proteins. , 2004, Current opinion in structural biology.

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

[26]  J. Wojcik,et al.  The protein–protein interaction map of Helicobacter pylori , 2001, Nature.

[27]  S. Fields,et al.  The two-hybrid system: a method to identify and clone genes for proteins that interact with a protein of interest. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[28]  Christian von Mering,et al.  STRING: a database of predicted functional associations between proteins , 2003, Nucleic Acids Res..

[29]  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.

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

[31]  E. Myers,et al.  Basic local alignment search tool. , 1990, Journal of molecular biology.

[32]  Gene Ontology Consortium The Gene Ontology (GO) database and informatics resource , 2003 .

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

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

[35]  A. Emili,et al.  Interaction network containing conserved and essential protein complexes in Escherichia coli , 2005, Nature.

[36]  Charles DeLisi,et al.  Predictome: a database of putative functional links between proteins , 2002, Nucleic Acids Res..

[37]  M. Tyers,et al.  Osprey: a network visualization system , 2003, Genome Biology.

[38]  Cheng-Yan Kao,et al.  POINT: a database for the prediction of protein-protein interactions based on the orthologous interactome , 2004, Bioinform..

[39]  Gabriele Ausiello,et al.  MINT: the Molecular INTeraction database , 2006, Nucleic Acids Res..

[40]  M. Gerstein,et al.  Annotation transfer for genomics: measuring functional divergence in multi-domain proteins. , 2001, Genome research.

[41]  Christian von Mering,et al.  STRING: known and predicted protein–protein associations, integrated and transferred across organisms , 2004, Nucleic Acids Res..

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

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