Yu, HY; Luscombe, NM; Lu, HX; Zhu, XW; Xia, Y; Han, JDJ; Bertin, N; Chung, S; Vidal, M; Gerstein, M
Annotation transfer between genomes: Protein-protein interologs and protein-DNA regulogs
Teil von
  • Genome research, 2004-06-01, Vol.14 (6), p.1107-1118
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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 oil 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 ail online database at 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.

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