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Inferring Ancestral Protein Interaction Networks

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Part of the Methods in Molecular Biology™ book series (MIMB,volume 452)


With the recent sequencing of numerous complete genomes and the advent of high throughput technologies (e.g., yeast two-hybrid assays or tandem-affinity purification experiments), it is now possible to estimate the ancestral form of protein interaction networks. This chapter combines protein interaction data and comparative genomics techniques in an attempt to reconstruct a network of core proteins and interactions in yeast that potentially represents an ancestral state of the budding yeast protein interaction network.

Key words

  • Ancestral state
  • protein interaction networks
  • phylogenetic profiles
  • comparative genomics
  • bioinformatics

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  1. Uetz, P., Giot, L., Cagney, G., et al. (2000) A comprehensive analysis of protein-protein interactions in Saccharomyces cerevisiae. Nature 403, 623–627.

    CrossRef  PubMed  CAS  Google Scholar 

  2. Gavin, A. C., Bosche, M., Krause, R., et al. (2002) Functional organization of the yeast proteome by systematic analysis of protein complexes. Nature 415, 141–147.

    CrossRef  PubMed  CAS  Google Scholar 

  3. Giot, L., Bader, J. S., Brouwer, C., et al. (2003) A protein interaction map of Drosophila melanogaster. Science 302, 1727–1736.

    CrossRef  PubMed  CAS  Google Scholar 

  4. Li, S., Armstrong, C. M., Bertin, N., et al. (2004) A map of the interactome network of the metazoan C. elegans. Science 303, 540–543.

    CrossRef  PubMed  CAS  Google Scholar 

  5. Butland, G., Peregrin-Alvarez, J. M., Li, J., et al. (2005) Interaction network containing conserved and essential protein complexes in Escherichia coli. Nature 433, 531–537.

    CrossRef  Google Scholar 

  6. Pereira-Leal, J. B., Audit, B., Peregrin-Alvarez, J. M., et al. (2005) An exponential core in the heart of the yeast protein interaction network. Mol Biol Evol 22, 421–425.

    CrossRef  PubMed  CAS  Google Scholar 

  7. Peregrin-Alvarez, J. M., Tsoka, S., Ouzounis, C. A. (2003) The phylogenetic extent of metabolic enzymes and pathways. Genome Res 13, 422–427.

    CrossRef  PubMed  CAS  Google Scholar 

  8. Makarova, K. S., Aravind, L., Galperin, M. Y., et al. (1999) Comparative genomics of the Archaea (Euryarchaeota): evolution of conserved protein families, the stable core, and the variable shell. Genome Res 9, 608–628.

    PubMed  CAS  Google Scholar 

  9. Harris, J. K., Kelley, S. T., Spiegelman, G. B., et al. (2003) The genetic core of the universal ancestor. Genome Res 13, 407– 412.

    CrossRef  PubMed  CAS  Google Scholar 

  10. Kyrpides, N., Overbeek, R., Ouzounis, C. (1999) Universal protein families and the functional content of the last universal common ancestor. J Mol Evol 49, 413–423.

    CrossRef  PubMed  CAS  Google Scholar 

  11. Deane, C. M., Salwinski, L., Xenarios, I., et al. (2002) Protein interactions: two methods for assessment of the reliability of high-throughput observations. Mol Cell Prot 1, 349–356.

    CrossRef  CAS  Google Scholar 

  12. Altschul, S. F., Gish, W., Miller, W., et al. (1990) Basic local alignment search tool. J Mol Biol 215, 403–410.

    PubMed  CAS  Google Scholar 

  13. Goldovsky, L., Cases, I., Enright, A. J., et al. (2005) BioLayout (Java): versatile network visualisation of structural and functional relationships. Appl Bioinformatics 4, 71–74.

    CrossRef  PubMed  CAS  Google Scholar 

  14. Pellegrini, M., Marcotte, E. M., Thompson, M. J., et al. (1999) Assigning protein functions by comparative genome analysis: protein phylogenetic profiles. Proc Natl Acad Sci U S A 96, 4285–4288.

    CrossRef  PubMed  CAS  Google Scholar 

  15. Woese, C. (1998) The universal ancestor. Proc Natl Acad Sci U S A 9, 6854–6859.

    CrossRef  Google Scholar 

  16. Ouzounis, C. A., Kunin, V., Darzentas, N., et al. (2005) A minimal estimate for the gene content of the last common ancestor: exobiology from a terrestrial perspective. Res Microbiol 2005; Epub ahead of print.

    Google Scholar 

  17. Ouzounis, C. A. (2005) Ancestral state reconstructions for genomes. Curr Opin Genet Dev 15, 595–600.

    CrossRef  PubMed  CAS  Google Scholar 

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The author thanks John Parkinson for reading the manuscript and making useful comments. This work was supported by the Hospital for Sick Children (Toronto, Ontario, Canada) Research Training Center.

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© 2008 Humana Press, a part of Springer Science+Business Media, LLC

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Peregrín-Alvarez, J.M. (2008). Inferring Ancestral Protein Interaction Networks. In: Keith, J.M. (eds) Bioinformatics. Methods in Molecular Biology™, vol 452. Humana Press.

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  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-707-5

  • Online ISBN: 978-1-60327-159-2

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