This Article Full Text Full Text (PDF) Supplemental Research Data Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yu, H. Articles by Gerstein, M. Search for Related Content PubMed PubMed Citation Articles by Yu, H. Articles by Gerstein, M. Social Bookmarking                   What's this?

Methods

Annotation Transfer Between Genomes: Protein–Protein Interologs and Protein–DNA Regulogs

¹ Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA ² Dana-Farber Cancer Institute and Department of Genetics, Harvard Medical School, Boston 02115, Massachusetts, USA

Proteins function mainly through interactions, especially with DNA and other proteins. While some large-scale interaction networks are now available for a number of model organisms, their experimental generation remains difficult. Consequently, interolog mapping—the transfer of interaction annotation from one organism to another using comparative genomics—is of significant value. Here we quantitatively assess the degree to which interologs can be reliably transferred between species as a function of the sequence similarity of the corresponding interacting proteins. Using interaction information from Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, and Helicobacter pylori, we find that protein–protein interactions can be transferred when a pair of proteins has a joint sequence identity >80% or a joint E-value <10^–70. (These "joint" quantities are the geometric means of the identities or E-values for the two pairs of interacting proteins.) We generalize our interolog analysis to protein–DNA binding, finding such interactions are conserved at specific thresholds between 30% and 60% sequence identity depending on the protein family. Furthermore, we introduce the concept of a "regulog"—a conserved regulatory relationship between proteins across different species. We map interologs and regulogs from yeast to a number of genomes with limited experimental annotation (e.g., Arabidopsis thaliana) and make these available through an online database at http://interolog.gersteinlab.org. Specifically, we are able to transfer 90,000 potential protein–protein interactions to the worm. We test a number of these in two-hybrid experiments and are able to verify 45 overlaps, which we show to be statistically significant.

³ Corresponding author.
E-MAIL Mark.Gerstein{at}yale.edu; FAX 1 360 838 7861.

[Supplemental material is available online at www.genome.org. The interologs and regulogs mapped from yeast to other genomes are available online at http://interolog.gersteinlab.org.]

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				C. Su, J. M. Peregrin-Alvarez, G. Butland, S. Phanse, V. Fong, A. Emili, and J. Parkinson Bacteriome.org an integrated protein interaction database for E. coli Nucleic Acids Res., January 11, 2008; 36(suppl_1): D632 - D636. [Abstract] [Full Text] [PDF]

				A. Ruepp, B. Brauner, I. Dunger-Kaltenbach, G. Frishman, C. Montrone, M. Stransky, B. Waegele, T. Schmidt, O. N. Doudieu, V. Stumpflen, et al. CORUM: the comprehensive resource of mammalian protein complexes Nucleic Acids Res., January 11, 2008; 36(suppl_1): D646 - D650. [Abstract] [Full Text] [PDF]

				F. P. Davis, D. T. Barkan, N. Eswar, J. H. McKerrow, and A. Sali Host pathogen protein interactions predicted by comparative modeling Protein Sci., December 1, 2007; 16(12): 2585 - 2596. [Abstract] [Full Text] [PDF]

				J. Geisler-Lee, N. O'Toole, R. Ammar, N. J. Provart, A. H. Millar, and M. Geisler A Predicted Interactome for Arabidopsis Plant Physiology, October 1, 2007; 145(2): 317 - 329. [Abstract] [Full Text] [PDF]

				B. S. Srinivasan, N. H. Shah, J. A. Flannick, E. Abeliuk, A. F. Novak, and S. Batzoglou Current progress in network research: toward reference networks for key model organisms Brief Bioinform, September 1, 2007; 8(5): 318 - 332. [Abstract] [Full Text] [PDF]

				M. D. Dyer, T. M. Murali, and B. W. Sobral Computational prediction of host-pathogen protein protein interactions Bioinformatics, July 1, 2007; 23(13): i159 - i166. [Abstract] [Full Text] [PDF]

				C. Tian, T. Kasuga, M. S. Sachs, and N. L. Glass Transcriptional Profiling of Cross Pathway Control in Neurospora crassa and Comparative Analysis of the Gcn4 and CPC1 Regulons Eukaryot. Cell, June 1, 2007; 6(6): 1018 - 1029. [Abstract] [Full Text] [PDF]

				X. Zhu, M. Gerstein, and M. Snyder Getting connected: analysis and principles of biological networks Genes & Dev., May 1, 2007; 21(9): 1010 - 1024. [Abstract] [Full Text] [PDF]

				A. Schlicker, C. Huthmacher, F. Ramirez, T. Lengauer, and M. Albrecht Functional evaluation of domain domain interactions and human protein interaction networks Bioinformatics, April 1, 2007; 23(7): 859 - 865. [Abstract] [Full Text] [PDF]

				K. Tan, T. Shlomi, H. Feizi, T. Ideker, and R. Sharan Transcriptional regulation of protein complexes within and across species PNAS, January 23, 2007; 104(4): 1283 - 1288. [Abstract] [Full Text] [PDF]

				Z. Liang, M. Xu, M. Teng, and L. Niu NetAlign: a web-based tool for comparison of protein interaction networks Bioinformatics, September 1, 2006; 22(17): 2175 - 2177. [Abstract] [Full Text] [PDF]

				I. Lozada-Chavez, S. C. Janga, and J. Collado-Vides Bacterial regulatory networks are extremely flexible in evolution Nucleic Acids Res., July 13, 2006; 34(12): 3434 - 3445. [Abstract] [Full Text] [PDF]

				O. Mendez, B. Martin, R. Sanz, R. Aragues, V. Moreno, B. Oliva, V. Stresing, and A. Sierra Underexpression of transcriptional regulators is common in metastatic breast cancer cells overexpressing Bcl-xL Carcinogenesis, June 1, 2006; 27(6): 1169 - 1179. [Abstract] [Full Text] [PDF]

				F. P. Davis, H. Braberg, M.-Y. Shen, U. Pieper, A. Sali, and M.S. Madhusudhan Protein complex compositions predicted by structural similarity Nucleic Acids Res., May 31, 2006; 34(10): 2943 - 2952. [Abstract] [Full Text] [PDF]

				R. Aragues, D. Jaeggi, and B. Oliva PIANA: protein interactions and network analysis Bioinformatics, April 15, 2006; 22(8): 1015 - 1017. [Abstract] [Full Text] [PDF]

				R. Jothi, E. Zotenko, A. Tasneem, and T. M. Przytycka COCO-CL: hierarchical clustering of homology relations based on evolutionary correlations Bioinformatics, April 1, 2006; 22(7): 779 - 788. [Abstract] [Full Text] [PDF]

				D. R. Boverhof and T. R. Zacharewski Toxicogenomics in Risk Assessment: Applications and Needs Toxicol. Sci., February 1, 2006; 89(2): 352 - 360. [Abstract] [Full Text] [PDF]

				U. Guldener, M. Munsterkotter, M. Oesterheld, P. Pagel, A. Ruepp, H.-W. Mewes, and V. Stumpflen MPact: the MIPS protein interaction resource on yeast Nucleic Acids Res., January 1, 2006; 34(suppl_1): D436 - D441. [Abstract] [Full Text] [PDF]

				K. Dolinski and D. Botstein Changing perspectives in yeast research nearly a decade after the genome sequence Genome Res., December 1, 2005; 15(12): 1611 - 1619. [Abstract] [Full Text] [PDF]

				J. C. Kwekel, L. D. Burgoon, J. W. Burt, J. R. Harkema, and T. R. Zacharewski A cross-species analysis of the rodent uterotrophic program: elucidation of conserved responses and targets of estrogen signaling Physiol Genomics, November 17, 2005; 23(3): 327 - 342. [Abstract] [Full Text] [PDF]

				M. E. Cusick, N. Klitgord, M. Vidal, and D. E. Hill Interactome: gateway into systems biology Hum. Mol. Genet., October 15, 2005; 14(suppl_2): R171 - R181. [Abstract] [Full Text] [PDF]

				P. Wong, A. Fritz, and D. Frishman Designability, aggregation propensity and duplication of disease-associated proteins Protein Eng. Des. Sel., October 1, 2005; 18(10): 503 - 508. [Abstract] [Full Text] [PDF]

				L. Espana, B. Martin, R. Aragues, C. Chiva, B. Oliva, D. Andreu, and A. Sierra Bcl-xL-Mediated Changes in Metabolic Pathways of Breast Cancer Cells: From Survival in the Blood Stream to Organ-Specific Metastasis Am. J. Pathol., October 1, 2005; 167(4): 1125 - 1137. [Abstract] [Full Text] [PDF]

				J. McDermott, R. Bumgarner, and R. Samudrala Functional annotation from predicted protein interaction networks Bioinformatics, August 1, 2005; 21(15): 3217 - 3226. [Abstract] [Full Text] [PDF]

				L. J. Lu, Y. Xia, A. Paccanaro, H. Yu, and M. Gerstein Assessing the limits of genomic data integration for predicting protein networks Genome Res., July 1, 2005; 15(7): 945 - 953. [Abstract] [Full Text] [PDF]

				M. Medina Genomes, phylogeny, and evolutionary systems biology PNAS, May 3, 2005; 102(suppl_1): 6630 - 6635. [Abstract] [Full Text] [PDF]

				K. R. Brown and I. Jurisica Online Predicted Human Interaction Database Bioinformatics, May 1, 2005; 21(9): 2076 - 2082. [Abstract] [Full Text] [PDF]

				R. Sharan, S. Suthram, R. M. Kelley, T. Kuhn, S. McCuine, P. Uetz, T. Sittler, R. M. Karp, and T. Ideker From the Cover: Conserved patterns of protein interaction in multiple species PNAS, February 8, 2005; 102(6): 1974 - 1979. [Abstract] [Full Text] [PDF]

				H.-W. Ma, B. Kumar, U. Ditges, F. Gunzer, J. Buer, and A.-P. Zeng An extended transcriptional regulatory network of Escherichia coli and analysis of its hierarchical structure and network motifs Nucleic Acids Res., December 16, 2004; 32(22): 6643 - 6649. [Abstract] [Full Text] [PDF]