Path finding methods accounting for stoichiometry in metabolic networks 英文参考文献.docVIP

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Path finding methods accounting for stoichiometry in metabolic networks 英文参考文献.doc

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Path finding methods accounting for stoichiometry in metabolic networks 英文参考文献

Peyetal.GenomeBiology2011,12:R49 /2011/12/5/R49 METHOD OpenAccess Pathfindingmethodsaccountingfor stoichiometryinmetabolicnetworks JonPey1,JoaquínPrada1,JohnEBeasley2* andFranciscoJPlanes1* Abstract Graph-basedmethodshavebeenwidelyusedfortheanalysisofbiologicalnetworks.Theirapplicationtometabolic networkshasbeenmuchdiscussed,inparticularnotingthatanimportantweaknessinsuchmethodsisthat reactionstoichiometryisneglected.Inthisstudy,weshowthatreactionstoichiometrycanbeincorporatedinto path-findingapproachesviamixed-integerlinearprogramming.Thismajoradvanceatthemodelinglevelresultsin improvedpredictionoftopologicalandfunctionalpropertiesinmetabolicnetworks. Background definitionofconnectivityisdebatable,however,particu- Theuseofgraphtheoryintheanalysisofbiologicalnet- larlywhenitisclaimedthatsuchapathisacompetent workshasbeenextensiveinthepastdecade[1].Particu- metabolicpathway,asrecentlydiscussed[25-27].Inthis larly, in metabolic networks different relevant topics context, the major criticism raised as to path-finding havebeenexaminedusingtherichvarietyofgraph-the- methodsisthattheyneglectreactionstoichiometryand oretic concepts, ranging from topological properties thereis,therefore,noguaranteethatanypathfoundcan [2-5], evolutionary analysis [6-8], pathway analysis operateinsustainedsteady-state. [9-13], transcriptional regulation [14-16], functional interpretation of‘omics’data [17-20] andprediction of the boundary of the metabolic network under study. noveldrugtargets[21-23]. Metabolitesinsidetheboundaryofthenetwork,typically Thesteady-state condition requires thedefinition of Graph-basedmethodsstartbyconvertingthemetabolic calledinternalmetabolites[28],mustbeinstoichiometric networkintoanappropriategraph.Differentrepresenta- balance.Balancingdoesnotapplytometabolitesoutside tionsarepossiblehere:i)metabolitegraphs,wherenodes the boundaries of the system (external metabolites), aremetabolites andarcsrepresent reactions link