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H Inferring protein-protein interactions through high-throughput interaction data from dive.pdf

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H Inferring protein-protein interactions through high-throughput interaction data from dive

1Inferring protein-protein interactions through high-throughput interaction data from diverse organisms Yin Liu1, Nianjun Liu2, Hongyu Zhao2,3,* 1Program of Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA 2Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06520, USA 3Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA *To whom correspondence should be addressed. Keywords: domain, likelihood, high-throughput data, protein-protein interaction ? The Author (2005). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@ Bioinformatics Advance Access published May 19, 2005 2ABSTRACT Motivation: Identifying protein-protein interactions is critical for understanding cellular processes. Because protein domains represent binding modules and are responsible for the interactions between proteins, computational approaches have been proposed to predict protein interactions at the domain level. The fact that protein domains are likely evolutionarily conserved allows us to pool information from data across multiple organisms for the inference of domain-domain and protein-protein interaction probabilities. Results: We use a likelihood approach to estimating domain-domain interaction probabilities by integrating large-scale protein interaction data from three organisms, S. cerevisiae, C. elegans, and D. melanogaster. The estimated domain-domain interaction probabilities are then used to predict protein-protein interactions in S. cerevisiae. Based on a thorough comparison of sensitivity and specificity, Gene Ontology term enrichment and gene expression profiles, we have demonstrated that it may be far more informative to predict protein-protein interactions from diverse organisms than that based on a single organism. Availability: The program for computing the protein-protein interaction prob