Building and analyzing protein interactome networks by cross-species comparisons.
BACKGROUND
A genomic catalogue of protein-protein interactions is a rich source of information, particularly for exploring the relationships between proteins. Numerous systems-wide and small-scale experiments have been conducted to identify interactions; however, our knowledge of all interactions for any one species is incomplete, and alternative means to expand these network maps is needed. We therefore took a comparative biology approach to predict protein-protein interactions across five species (human, mouse, fly, worm, and yeast) and developed InterologFinder for research biologists to easily navigate this data. We also developed a confidence score for interactions based on available experimental evidence and conservation across species.


RESULTS
The connectivity of the resultant networks was determined to have scale-free distribution, small-world properties, and increased local modularity, indicating that the added interactions do not disrupt our current understanding of protein network structures. We show examples of how these improved interactomes can be used to analyze a genome-scale dataset (RNAi screen) and to assign new function to proteins. Predicted interactions within this dataset were tested by co-immunoprecipitation, resulting in a high rate of validation, suggesting the high quality of networks produced.


CONCLUSIONS
Protein-protein interactions were predicted in five species, based on orthology. An InteroScore, a score accounting for homology, number of orthologues with evidence of interactions, and number of unique observations of interactions, is given to each known and predicted interaction. Our website http://www.interologfinder.org provides research biologists intuitive access to this data.
Wiles
Amy M
AM
Greehey Children's Cancer Research Institute, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
Doderer
Mark
M
Ruan
Jianhua
J
Gu
Ting-Ting
TT
Ravi
Dashnamoorthy
D
Blackman
Barron
B
Bishop
Alexander J R
AJ
D000818:Animals; D017173:Caenorhabditis elegans; D019295:Computational Biology / Q000379:methods*; D004330:Drosophila; D006801:Humans; D051379:Mice; D015233:Models, Statistical; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry; D025941:Protein Interaction Mapping / Q000379:methods*; D011506:Proteins / Q000737:chemistry*; D034622:RNA Interference; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D012984:Software; D013045:Species Specificity; D014162:Transfection
D011506:Proteins; D046988:Proteasome Endopeptidase Complex