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Bioinformatics Advance Access published online on June 12, 2008
Bioinformatics, doi:10.1093/bioinformatics/btn286
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© The Author (2008). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Ensemble Non-negative Matrix Factorization Methods for Clustering Protein-Protein Interactions

Derek Greene 1,*, Gerard Cagney 2,3, Nevan Krogan 3 and Pádraig Cunningham 1

1School of Computer Science and Informatics, University College Dublin, Ireland
2Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Ireland
3Department of Cellular and Molecular Pharmacology, University of California, San Francisco

*To whom correspondence should be addressed. Dr. Derek Greene, E-mail: derek.greene{at}ucd.ie


  Abstract

Motivation: When working with large-scale protein interaction data, an important analysis task is the assignment of pairs of proteins to groups that correspond to higher order assemblies. Previously a common approach to this problem has been to apply standard hierarchical clustering methods to identify such a groups. Here we propose a new algorithm for aggregating a diverse collection of matrix factorizations to produce a more informative clustering, which takes the form of a "soft" hierarchy of clusters.

Results: We apply the proposed Ensemble NMF algorithm to a high-quality assembly of binary protein interactions derived from two proteome-wide studies in yeast. Our experimental evaluation demonstrates that the algorithm lends itself to discovering small localized structures in this data, which correspond to known functional groupings of complexes. In addition, we show that the algorithm also supports the assignment of putative functions for previously uncharacterized proteins, for instance the protein YNR024W, which may be an uncharacterized component of the exosome.

Contact: derek.greene{at}ucd.ie

Supplementary information: http://mlg.ucd.ie/nmf

Associate Editor: Dr. Jonathan Wren

Received on April 3, 2008; revised on May 15, 2008; accepted on June 8, 2008

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