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

Hsing M, Byler KG, Cherkasov A - BMC Syst Biol (2008)

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Faculty of Graduate Studies, Bioinformatics Graduate Program, University of British Columbia, Vancouver, BC, Canada. mhsing@interchange.ubc.ca

ABSTRACT

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) 12. 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.

Show MeSH

Related in: MedlinePlus

Accumulative protein interaction distribution plots. a) E. coli, b) S. cerevisiae, c) D. melanogaster, d) H. sapiens. On each plot, the (x, y) coordinate of the sharp turn or the inflection point is shown.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2553323&req=5

Figure 1: Accumulative protein interaction distribution plots. a) E. coli, b) S. cerevisiae, c) D. melanogaster, d) H. sapiens. On each plot, the (x, y) coordinate of the sharp turn or the inflection point is shown.

Mentions: Hub proteins were identified based on their numbers of protein interactions and their percentile ranking relative to other proteins in the same species. Proteins of the same species were divided into different percentile groups, sorted by the number of protein-protein interactions in a decreasing order (ie. higher percentile proteins have more interactions than lower percentile proteins). It is clear that hub proteins have more interactions than non-hubs, but currently there is no consensus on exactly how many interactions a hub protein should have. Often, hubs are defined arbitrarily to have at least certain number of interactions [40]. In our study, the hub selection criterion was based on the position of a sharp turn (or inflection point) on an accumulative protein interaction distribution plot from each of the four species. As shown in Figure 1, the protein interactions followed a power law distribution, such that a sharp turn is visible around the 90th protein percentile position on the interaction plots.


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

Hsing M, Byler KG, Cherkasov A - BMC Syst Biol (2008)

Accumulative protein interaction distribution plots. a) E. coli, b) S. cerevisiae, c) D. melanogaster, d) H. sapiens. On each plot, the (x, y) coordinate of the sharp turn or the inflection point is shown.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2553323&req=5

Figure 1: Accumulative protein interaction distribution plots. a) E. coli, b) S. cerevisiae, c) D. melanogaster, d) H. sapiens. On each plot, the (x, y) coordinate of the sharp turn or the inflection point is shown.
Mentions: Hub proteins were identified based on their numbers of protein interactions and their percentile ranking relative to other proteins in the same species. Proteins of the same species were divided into different percentile groups, sorted by the number of protein-protein interactions in a decreasing order (ie. higher percentile proteins have more interactions than lower percentile proteins). It is clear that hub proteins have more interactions than non-hubs, but currently there is no consensus on exactly how many interactions a hub protein should have. Often, hubs are defined arbitrarily to have at least certain number of interactions [40]. In our study, the hub selection criterion was based on the position of a sharp turn (or inflection point) on an accumulative protein interaction distribution plot from each of the four species. As shown in Figure 1, the protein interactions followed a power law distribution, such that a sharp turn is visible around the 90th protein percentile position on the interaction plots.

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Faculty of Graduate Studies, Bioinformatics Graduate Program, University of British Columbia, Vancouver, BC, Canada. mhsing@interchange.ubc.ca

ABSTRACT

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) 12. 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.

Show MeSH
Related in: MedlinePlus