Computational verification of protein-protein interactions by orthologous co-expression.
BACKGROUND
High-throughput methods identify an overwhelming number of protein-protein interactions. However, the limited accuracy of these methods results in the false identification of many spurious interactions. Accordingly, the resulting interactions are regarded as hypothetical and computational methods are needed to increase their confidence. Several methods have recently been suggested for this purpose including co-expression as a confidence measure for interacting proteins, but their performance is still quite poor.


RESULTS
We introduce a novel computational method for verification of protein-protein interactions based on the co-expression of orthologs of interacting partners. The performance of our method is analysed using known S. cerevisiae interactions, and is shown to overcome limitations of previous methods. We present specific examples of known and putative interactions that are detected by our method and not by previous methods, and suggest that they represent transient interactions that might have been conserved and stabilized in other species.


CONCLUSIONS
Co-expression of orthologous protein-pairs can be used to increase the confidence of hypothetical protein-protein interactions in S. cerevisiae as well as in other species. This approach may be especially useful for species with no available expression profiles and for transient interactions.
Tirosh
Itay
I
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel. itay.tirosh@weizmann.ac.il <itay.tirosh@weizmann.ac.il>
Barkai
Naama
N
D000818:Animals; D001665:Binding Sites; D003001:Cloning, Molecular; D019295:Computational Biology / Q000379:methods*; D003196:Computer Graphics; D030541:Databases, Genetic; D030562:Databases, Protein; D005656:Fungal Proteins / Q000737:chemistry; D015870:Gene Expression; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D006801:Humans; D008957:Models, Genetic; D015233:Models, Statistical; D008968:Molecular Conformation; D011485:Protein Binding; D017510:Protein Folding; D025941:Protein Interaction Mapping / Q000379:methods*; D011506:Proteins / Q000737:chemistry; D040901:Proteomics; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D016415:Sequence Alignment; D012984:Software
D005656:Fungal Proteins; D011506:Proteins
Nucleic Acids Res. 2004 Jul 1;32(Web Server issue):W69-72
15215353
Proc Natl Acad Sci U S A. 2004 Jun 15;101(24):9033-8
15175431
Yeast. 1999 Mar 30;15(5):397-407
10219998
Cell. 1998 Jul 10;94(1):35-44
9674425
Nature. 2000 Feb 10;403(6770):623-7
10688190
J Mol Biol. 2000 Jun 2;299(2):283-93
10860738
Mol Biol Evol. 2000 Jul;17(7):1061-74
10889219
Nat Rev Mol Cell Biol. 2001 Mar;2(3):202-10
11265250
Proc Natl Acad Sci U S A. 2001 Apr 10;98(8):4569-74
11283351
Mol Cell Biol. 2001 Nov;21(21):7331-44
11585915
Nat Genet. 2001 Dec;29(4):482-6
11694880
Genome Res. 2001 Dec;11(12):1971-3
11731485
Genome Res. 2001 Dec;11(12):2120-6
11731503
Nucleic Acids Res. 2002 Jan 1;30(1):31-4
11752246
Genome Res. 2002 Jan;12(1):37-46
11779829
Nature. 2002 Jan 10;415(6868):141-7
11805826
Nature. 2002 Jan 10;415(6868):180-3
11805837
Nature. 2002 May 23;417(6887):399-403
12000970
Mol Cell. 2002 May;9(5):1133-43
12049748
Mol Cell Proteomics. 2002 May;1(5):349-56
12118076
J Mol Biol. 2003 Apr 11;327(5):919-23
12662919
Curr Opin Struct Biol. 2003 Jun;13(3):377-82
12831890
Science. 2003 Oct 10;302(5643):249-55
12934013
Science. 2003 Dec 5;302(5651):1727-36
14605208
Science. 2004 Jan 23;303(5657):540-3
14704431
Trends Genet. 2004 Feb;20(2):72-6
14746987
PLoS Biol. 2004 Jan;2(1):E9
14737187
BMC Bioinformatics. 2004 Apr 16;5:38
15090078
Nucleic Acids Res. 1997 Sep 1;25(17):3389-402
9254694