Annotation transfer between genomes: protein-protein interologs and protein-DNA regulogs.
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 approximately 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.
Yu
Haiyuan
H
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA.
Luscombe
Nicholas M
NM
Lu
Hao Xin
HX
Zhu
Xiaowei
X
Xia
Yu
Y
Han
Jing-Dong J
JD
Bertin
Nicolas
N
Chung
Sambath
S
Vidal
Marc
M
Gerstein
Mark
M
D000595:Amino Acid Sequence / Q000502:physiology; D000818:Animals; D001426:Bacterial Proteins / Q000502:physiology; D001665:Binding Sites / Q000502:physiology; D017173:Caenorhabditis elegans / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000502:physiology; D019295:Computational Biology / Q000379:methods / Q000706:statistics & numerical data; D017124:Conserved Sequence / Q000502:physiology; D004247:DNA / Q000502:physiology*; D004269:DNA, Bacterial / Q000502:physiology; D004271:DNA, Fungal / Q000502:physiology; D018509:DNA, Helminth / Q000502:physiology; D004268:DNA-Binding Proteins / Q000502:physiology*; D030562:Databases, Protein; D029721:Drosophila Proteins / Q000502:physiology; D004331:Drosophila melanogaster / Q000235:genetics; D016678:Genome; D016680:Genome, Bacterial; D016681:Genome, Fungal; D016480:Helicobacter pylori / Q000235:genetics; D011485:Protein Binding / Q000502:physiology; D025941:Protein Interaction Mapping / Q000379:methods / Q000706:statistics & numerical data; D011506:Proteins / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000502:physiology; D017386:Sequence Homology, Amino Acid
D001426:Bacterial Proteins; D029742:Caenorhabditis elegans Proteins; D004269:DNA, Bacterial; D004271:DNA, Fungal; D018509:DNA, Helminth; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D011506:Proteins; D029701:Saccharomyces cerevisiae Proteins; D004247:DNA