Fault Tolerance in Protein Interaction Networks Stable Bipartite Subgraphs and Redundant Pathways 英文参考文献.docVIP

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Fault Tolerance in Protein Interaction Networks Stable Bipartite Subgraphs and Redundant Pathways 英文参考文献.doc

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Fault Tolerance in Protein Interaction Networks Stable Bipartite Subgraphs and Redundant Pathways 英文参考文献

FaultToleranceinProteinInteractionNetworks:Stable BipartiteSubgraphsandRedundantPathways ArthurBrady1*,KyleMaxwell2,NoahDaniels2,LenoreJ.Cowen2* 1CenterforBioinformaticsandComputationalBiology,UniversityofMaryland,CollegePark,Maryland,UnitedStatesofAmerica, 2DepartmentofComputerScience, TuftsUniversity,Medford,Massachusetts,UnitedStatesofAmerica Abstract Asincreasingamountsofhigh-throughputdatafortheyeastinteractomebecomeavailable,moresystem-wideproperties areuncovered.Oneinterestingquestionconcernsthefaulttoleranceofproteininteractionnetworks:whetherthereexist alternative pathways that can perform some required function if a gene essential to the main mechanism is defective, absentorsuppressed.AsignaturepatternforredundantpathwaysistheBPM(between-pathwaymodel)motif,introduced byKelleyandIdeker.PastmethodsproposedtosearchtheyeastinteractomeforBPMmotifshavehadseveralimportant limitations.First,theyhavebeendrivenheuristicallybylocalgreedysearches,whichcanleadtotheinclusionofextragenes thatmaynotbelonginthemotif;second,theyhavebeenvalidatedsolelybyfunctionalcoherenceoftheputativepathways usingGOenrichment,makingitdifficulttoevaluateputativeBPMsintheabsenceofalreadyknownbiologicalannotation. We introduce stable bipartite subgraphs, and show they form a clean and efficient way of generating meaningful BPMs whichnaturallydiscardextragenesincludedbylocalgreedymethods.WeshowbyGOenrichmentmeasuresthatourBPM setoutperformspreviouswork,coveringmoreknowncomplexesandfunctionalpathways.Perhapsmostimportantly,since ourBPMsareinitiallygeneratedbyexaminingthegenetic-interactionnetworkonly,thelocationofedgesintheprotein- proteinphysicalinteractionnetworkcanthenbeusedtostatisticallyvalidateeachcandidateBPM,evenwithsparseGO annotation(ornoneatall).Weuncoversomeinterestingbiologicalexamplesofpreviouslyunknownputativeredundant pathwaysinsuchareasasvesicle-mediatedtransportandDNArepair. Citation: Brady A, Maxwell K, Daniels N, Cowen LJ (2009) Fault Tolerance in Protein Interact