Interolog/Regulog Database

1.Abstract

Proteins function mainly through physical interactions, especially with DNA and other proteins. Large-scale networks of both types of interactions are now available for a number of model organisms, but the experimental generation of these networks is still difficult. Therefore, interolog mapping - the transfer of interaction information 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 sequence similarity of interacting proteins. Using interaction information from S. cerevisiae, C. elegans, D. melanogaster, and H. pylori, we find that protein-protein interactions can be reliably transferred when a pair of proteins has a joint sequence identity greater than 50% or a joint E-value smaller than 10-120. (These "joint" values are the geometric mean of the identities or E-values for the two pairs of interacting proteins.) We generalize our interolog analysis to protein-DNA binding, and find that 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 for which there are limited experimental data (e.g. A. thaliana) and make these available through an on-line database at http://genecensus.org/interactions/interolog/. Specifically, we are able to transfer about 90,000 potential protein-protein interactions to worm. We test a number of these in large-scale two-hybrid experiments. We are able to verify 45 overlaps, which we show to be statistically significant.