Abstract
We study the question of detecting Conserved Protein Interaction Modules (CPIMs) in protein-protein interaction (PPI) networks. We propose a novel algorithm called GraphHopper that analyzes two PPI networks to find CPIMs. GraphHopper finds CPIMs by “hopping” from one network to another using orthology relationships. By decoupling the degree of evolutionary conservation in a CPIM from the reliability of the PPIs in a CPIM, GraphHopper finds CPIMs with a wide variety of topologies that previous algorithms cannot detect.
GraphHopper is competitive with NetworkBlast and Match-and-Split, two state-of-the-art algorithms for computing CPIMs, on the task of recapitulating MIPS processes and complexes. Upon applying GraphHopper to human, fly, and yeast PPI networks, we find a number of CPIMs involved in fundamental processes of the cell that are conserved in all three species. We present the first global map of human-fly CPIMs. This map sheds light on the conservation of protein interaction modules in multi-cellular organisms. CPIMs related to development and the nervous system emerge only in the human-fly comparison. For example, a set of 10 interconnected CPIMs suggest that fly proteins involved in eye development may have human orthologs that have evolved functions related to blood clotting, vascular development, and structural support.
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References
Sharan, R., Ideker, T.: Modeling cellular machinery through biological network comparison. Nat. Biotechnol. 24(4), 427–433 (2006)
Kelley, B.P., Sharan, R., Karp, R.M., Sittler, T., Root, D.E., Stockwell, B.R., Ideker, T.: Conserved pathways within bacteria and yeast as revealed by global protein network alignment. Proc. Natl. Acad. Sci. U S A 100(20), 11394–11399 (2003)
Koyuturk, M., Kim, Y., Topkara, U., Subramaniam, S., Szpankowski, W., Grama, A.: Pairwise alignment of protein interaction networks. J. Comput. Biol. 13(2), 182–199 (2006)
Sharan, R., Ideker, T., Kelley, B.P., Shamir, R., Karp, R.M.: Identification of protein complexes by comparative analysis of yeast and bacterial protein interaction data. In: RECOMB 2004: Proceedings of the eighth annual international conference on Computational molecular biology, pp. 282–289. ACM Press, New York (2004)
Suthram, S., Shlomi, T., Ruppin, E., Sharan, R., Ideker, T.: A direct comparison of protein interaction confidence assignment schemes. BMC Bioinformatics 7, 360 (2006)
Narayanan, M., Karp, R.M.: Comparing Protein Interaction Networks via a Graph Match-and-Split Algorithm. J. Comput. Biol. 14(7), 892–907 (2007)
Koyuturk, M., Kim, Y., Subramaniam, S., Szpankowski, W., Grama, A.: Detecting conserved interaction patterns in biological networks. J. Comput. Biol. 13(7), 1299–1322 (2006)
Gandhi, T.K., et al.: Analysis of the human protein interactome and comparison with yeast, worm and fly interaction datasets. Nat. Genet. 38(3), 285–293 (2006)
Sharan, R., Suthram, S., Kelley, R.M., Kuhn, T., Mccuine, S., Uetz, P., Sittler, T., Karp, R.M., Ideker, T.: From the cover: Conserved patterns of protein interaction in multiple species. Proc. Natl. Acad. Sci. U S A 102(6), 1974–1979 (2005)
Guldener, U., Munsterkotter, M., Oesterheld, M., Pagel, P., Ruepp, A., Mewes, H.W., Stumpflen, V.: MPact: the MIPS protein interaction resource on yeast. Nucleic Acids Res. 34, D436–D441 (2006)
Goldberg, D.S., Roth, F.P.: Assessing experimentally derived interactions in a small world. Proc. Natl. Acad Sci. U S A 100(8), 4372–4376 (2003)
Ramani, A.K., Bunescu, R.C., Mooney, R.J., Marcotte, E.M.: Consolidating the set of known human protein-protein interactions in preparation for large-scale mapping of the human interactome. Genome Biol. 6(5), R40 (2005)
Stelzl, U., et al.: A human protein-protein interaction network: a resource for annotating the proteome. Cell 122(6), 957–968 (2005)
Rual, J., et al.: Towards a proteome-scale map of the human protein-protein interaction network. Nature 437(7062), 1173–1178 (2005)
Xenarios, I., Rice, D.W., Salwinski, L., Baron, M.K., Marcotte, E.M., Eisenberg, D.: DIP: the database of interacting proteins. Nucleic Acids Res. 28(1), 289–291 (2000)
Gansner, E.R., North, S.C.: An open graph visualization system and its applications to software engineering. Software – Practice and Experience 30(11), 1203–1233 (2000)
Araujo, S.J., Tear, G.: Axon guidance mechanisms and molecules: lessons from invertebrates. Nat. Rev. Neurosci. 4(11), 910–922 (2003)
Giot, L., et al.: A protein interaction map of drosophila melanogaster. Science 302(5651), 1727–1736 (2003)
Peri, S., et al.: Development of human protein reference database as an initial platform for approaching systems biology in humans. Genome Res. 13(10), 2363–2371 (2003)
Flannick, J., Novak, A., Srinivasan, B.S., McAdams, H.H., Batzoglou, S.: Graemlin: general and robust alignment of multiple large interaction networks. Genome Res. 16(9), 1169–1181 (2006)
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Rivera, C.G., Murali, T.M. (2009). Identifying Evolutionarily Conserved Protein Interaction Modules Using GraphHopper. In: Rajasekaran, S. (eds) Bioinformatics and Computational Biology. BICoB 2009. Lecture Notes in Computer Science(), vol 5462. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-00727-9_9
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DOI: https://doi.org/10.1007/978-3-642-00727-9_9
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