Nucleic Acids Research Advance Access originally published online on June 27, 2008
Nucleic Acids Research 2008 36(13):4286-4294; doi:10.1093/nar/gkn390
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Nucleic Acids Research, 2008, Vol. 36, No. 13 4286-4294
© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Computational Biology |
Global investigation of protein–protein interactions in yeast Saccharomyces cerevisiae using re-occurring short polypeptide sequences
1School of Computer Science, Carleton University, 2Department of Biology and Ottawa Institute of Systems Biology, Carleton University, Ottawa, Canada, 3Department of Mathematics and Computer Science, Fayetteville State University, Fayetteville, USA and 4Department of Systems and Computer Engineering, Carleton University, Ottawa, Canada
*To whom correspondence should be addressed. Tel: 613 520 2600; Fax: 613 520 3539; Email: ashkan_golshani{at}carleton.ca
Received March 12, 2008. Revised May 27, 2008. Accepted June 4, 2008.
Protein–protein interaction (PPI) maps provide insight into cellular biology and have received considerable attention in the post-genomic era. While large-scale experimental approaches have generated large collections of experimentally determined PPIs, technical limitations preclude certain PPIs from detection. Recently, we demonstrated that yeast PPIs can be computationally predicted using re-occurring short polypeptide sequences between known interacting protein pairs. However, the computational requirements and low specificity made this method unsuitable for large-scale investigations. Here, we report an improved approach, which exhibits a specificity of 
99.95% and executes 16 000 times faster. Importantly, we report the first all-to-all sequence-based computational screen of PPIs in yeast, Saccharomyces cerevisiae in which we identify 29 589 high confidence interactions of 2 x 107 possible pairs. Of these, 14 438 PPIs have not been previously reported and may represent novel interactions. In particular, these results reveal a richer set of membrane protein interactions, not readily amenable to experimental investigations. From the novel PPIs, a novel putative protein complex comprised largely of membrane proteins was revealed. In addition, two novel gene functions were predicted and experimentally confirmed to affect the efficiency of non-homologous end-joining, providing further support for the usefulness of the identified PPIs in biological investigations.
The authors wish it to be known that, in their opinion, the first two authors along with the last two authors should be regarded as joint First Authors