Conserved patterns of protein interaction in multiple species

  1. Roded Sharan*,,
  2. Silpa Suthram,
  3. Ryan M. Kelley,
  4. Tanja Kuhn§,
  5. Scott McCuine,
  6. Peter Uetz§,
  7. Taylor Sittler,
  8. Richard M. Karp*,, and
  9. Trey Ideker,
  1. *Computer Science Division, University of California, and International Computer Science Institute, 1947 Center Street, Berkeley, CA 94704; Department of Bioengineering, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093; and §Institute of Genetics, Research Center Karlsruhe, Postfach 3640, D-76021 Karlsruhe, Germany
  1. Contributed by Richard M. Karp, December 22, 2004

Abstract

To elucidate cellular machinery on a global scale, we performed a multiple comparison of the recently available protein–protein interaction networks of Caenorhabditis elegans, Drosophila melanogaster, and Saccharomyces cerevisiae. This comparison integrated protein interaction and sequence information to reveal 71 network regions that were conserved across all three species and many exclusive to the metazoans. We used this conservation, and found statistically significant support for 4,645 previously undescribed protein functions and 2,609 previously undescribed protein interactions. We tested 60 interaction predictions for yeast by two-hybrid analysis, confirming approximately half of these. Significantly, many of the predicted functions and interactions would not have been identified from sequence similarity alone, demonstrating that network comparisons provide essential biological information beyond what is gleaned from the genome.

Footnotes

  • To whom correspondence may be addressed. E-mail: karp{at}icsi.berkeley.edu or trey{at}bioeng.ucsd.edu.

  • Present address: School of Computer Science, Tel-Aviv University, Tel-Aviv 69978, Israel.

  • Author contributions: R.S., R.M. Karp, and T.I. designed research; R.S., S.S., R.M. Kelley, T.K., S.M., T.S., and T.I. performed research; R.S., S.S., R.M. Kelley, P.U., R.M. Karp, and T.I. contributed new reagents/analytic tools; R.S., S.S., R.M. Kelley, T.K., S.M., P.U., T.S., and T.I. analyzed data; and R.S., P.U., R.M. Karp, and T.I. wrote the paper.

  • Abbreviation: GO, gene ontology.

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