Global protein function prediction from protein-protein interaction networks (original) (raw)

Nature Biotechnology volume 21, pages 697–700 (2003)Cite this article

Abstract

Determining protein function is one of the most challenging problems of the post-genomic era. The availability of entire genome sequences and of high-throughput capabilities to determine gene coexpression patterns has shifted the research focus from the study of single proteins or small complexes to that of the entire proteome1. In this context, the search for reliable methods for assigning protein function is of primary importance. There are various approaches available for deducing the function of proteins of unknown function using information derived from sequence similarity or clustering patterns of co-regulated genes2,3, phylogenetic profiles4, protein-protein interactions (refs. 5–8 and Samanta, M.P. and Liang, S., unpublished data), and protein complexes9,10. Here we propose the assignment of proteins to functional classes on the basis of their network of physical interactions as determined by minimizing the number of protein interactions among different functional categories. Function assignment is proteome-wide and is determined by the global connectivity pattern of the protein network. The approach results in multiple functional assignments, a consequence of the existence of multiple equivalent solutions. We apply the method to analyze the yeast Saccharomyces cerevisiae protein-protein interaction network5. The robustness of the approach is tested in a system containing a high percentage of unclassified proteins and also in cases of deletion and insertion of specific protein interactions.

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Authors and Affiliations

  1. Department of Physics, University of Notre Dame, Notre Dame, 46556, Indiana, USA
    Alexei Vazquez
  2. International School for Advanced Studies (SISSA) and INFM, V. Beirut 2-4, Trieste, 34014, Italy
    Alexei Vazquez, Alessandro Flammini & Amos Maritan
  3. The Abdus Salam International Centre for Theoretical Physics, P.O. Box 586, Trieste, 34100, Italy
    Amos Maritan
  4. Laboratoire de Physique Théorique (UMR du CNRS 8627), Bâtiment 210 Université de Paris-Sud, Orsay, 91405, Cedex, France
    Alessandro Vespignani

Authors

  1. Alexei Vazquez
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  2. Alessandro Flammini
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  3. Amos Maritan
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  4. Alessandro Vespignani
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Correspondence toAlexei Vazquez.

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Vazquez, A., Flammini, A., Maritan, A. et al. Global protein function prediction from protein-protein interaction networks.Nat Biotechnol 21, 697–700 (2003). https://doi.org/10.1038/nbt825

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