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Open Access Highly Accessed Research article

Building and analyzing protein interactome networks by cross-species comparisons

Amy M Wiles1, Mark Doderer3, Jianhua Ruan3, Ting-Ting Gu1, Dashnamoorthy Ravi1, Barron Blackman1 and Alexander JR Bishop12*

Author Affiliations

1 Greehey Children's Cancer Research Institute, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA

2 Department of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA

3 Department of Computer Science, The University of Texas at San Antonio, San Antonio, TX 78249, USA

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BMC Systems Biology 2010, 4:36  doi:10.1186/1752-0509-4-36

Published: 30 March 2010

Abstract

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 webcite provides research biologists intuitive access to this data.