Protein–Protein Interactions More Conserved within Species than across Species 英文参考文献.docVIP
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Protein–Protein Interactions More Conserved within Species than across Species 英文参考文献
Protein–ProteinInteractionsMoreConserved
withinSpeciesthanacrossSpecies
Sven Mika1,2,*,Burkhard Rost2,3,4
1 Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York, United States of America, 2 Columbia University Center for
Computational Biology and Bioinformatics, Irvine Cancer Center, New York, New York, United States of America, 3 Institute of Physical Biochemistry, University Witten/
Herdecke,Witten,Germany,4NorthEastStructuralGenomicsConsortium,NewYork,NewYork,UnitedStatesofAmerica
Experimental high-throughput studies of protein–protein interactions are beginning to provide enough data for
comprehensive computational studies. Today, about ten large data sets, each with thousands of interacting pairs,
coarselysampletheinteractionsinfly,human,worm,andyeast.Anotherabout55,000pairsofinteractingproteins
have been identified by more careful, detailed biochemical experiments. Most interactions are experimentally
observed in prokaryotes and simple eukaryotes; very few interactions are observed in higher eukaryotes such as
mammals.Itiscommonlyassumedthatpathwaysinmammalscanbeinferredthroughhomologytomodelorganisms,
e.g.theexperimentalobservationthattwoyeastproteinsinteractistransferredtoinferthatthetwocorresponding
proteinsinhumanalsointeract.Twopairsforwhichtheinteractionisconservedareoftendescribedasinterologs.The
goal of this investigation was a large-scale comprehensive analysis of such inferences, i.e. of the evolutionary
conservation of interologs. Here, we introduced a novel score for measuring the overlap between protein–protein
interactiondatasets.Thismeasureappearedtoreflecttheoverallqualityofthedataandwasthebasisforourtwo
surprising results from our large-scale analysis. Firstly, homology-based inferences of physical protein–protein
interactionsappearedfarlesssuccessfulthanexpected.Infact,suchinferenceswereaccurateonlyforextremelyhigh
levels of sequence similarity. Secondly, and most surprisingly, the identification of i
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