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Background  Protein-protein interactions mediate a wide range of cellular functions and responses and have been studied rigorously through recent large-scale proteomics experiments and bioinformatics analyses. One of the most important findings of those endeavours was the observation that 'hub' proteins participate in significant numbers of protein interactions and play critical roles in the organization and function of cellular protein interaction networks (PINs) [ 1 , 2 ]. It has also been demonstrated that such hub proteins may constitute an important pool of attractive drug targets.  Thus, it is crucial to be able to identify hub proteins based not only on experimental data but also by means of bioinformatics predictions.    Results  A hub protein classifier has been developed based on the available interaction data and Gene Ontology (GO) annotations for proteins in the  Escherichia coli ,  Saccharomyces cerevisiae ,  Drosophila melanogaster  and  Homo sapiens  genomes. In particular, by utilizing the machine learning method of boosting trees we were able to create a predictive bioinformatics tool for the identification of proteins that are likely to play the role of a hub in protein interaction networks. Testing the developed hub classifier on external sets of experimental protein interaction data in Methicillin-resistant  Staphylococcus aureus  (MRSA) 252 and  Caenorhabditis elegans  demonstrated that our approach can predict hub proteins with a high degree of accuracy.  A practical application of the developed bioinformatics method has been illustrated by the effective protein bait selection for large-scale pull-down experiments that aim to map complete protein-protein interaction networks for several species.    Conclusion  The successful development of an accurate hub classifier demonstrated that highly-connected proteins tend to share certain relevant functional properties reflected in their Gene Ontology annotations. It is anticipated that the developed bioinformatics hub classifier will represent a useful tool for the theoretical prediction of highly-interacting proteins, the study of cellular network organizations, and the identification of prospective drug targets – even in those organisms that currently lack large-scale protein interaction data.

The use of Gene Ontology terms for predicting highly-connected 'hub' nodes in protein-protein interaction networks