PATHLOGIC-S A Scalable Boolean Framework for Modelling Cellular Signalling 英文参考文献.docVIP

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PATHLOGIC-S A Scalable Boolean Framework for Modelling Cellular Signalling 英文参考文献.doc

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PATHLOGIC-S A Scalable Boolean Framework for Modelling Cellular Signalling 英文参考文献

PATHLOGIC-S:AScalableBooleanFrameworkfor ModellingCellularSignalling LiamG.Fearnley,LarsK.Nielsen* AustralianInstituteofBioengineeringandNanotechnology,UniversityofQueensland,Brisbane,Queensland,Australia Abstract Curateddatabasesofsignaltransductionhavegrowntodescribeseveralthousandreactions,andefficientuseofthesedata requires the development of modelling tools to elucidate and explore system properties. We present PATHLOGIC-S, aBooleanspecificationforasignallingmodel,withitsassociatedGPL-licensedimplementationusingintegerprogramming techniques.ThePATHLOGIC-Sspecificationhasbeendesignedtofunctiononcurrentdesktopworkstations,andiscapable ofprovidinganalysesonsomeofthelargestcurrentlyavailabledatasetsthroughuseofBooleanmodellingtechniquesto generate predictions of stable and semi-stable network states from data in community file formats. PATHLOGIC-S also addressesmajorproblemsassociatedwiththepresenceandmodellingofinhibitioninBooleansystems,andreduceslogical incoherenceduetocommoninhibitorymechanismsinsignallingsystems.Weapplythisapproachtosignaltransduction networks including Reactome and two pathways from the Panther Pathways database, and present the results of computationsoneachalongwithadiscussionofexecutiontime.Asoftwareimplementationoftheframeworkandmodelis freelyavailableunderaGPLlicense. Citation: Fearnley LG, Nielsen LK (2012) PATHLOGIC-S: A Scalable Boolean Framework for Modelling Cellular Signalling. PLoS ONE 7(8): e41977. doi:10.1371/ journal.pone.0041977 Editor:PeterCsermely,SemmelweisUniversity,Hungary ReceivedApril27,2012;AcceptedJune27,2012;PublishedAugust7,2012 Copyright:?2012Fearnley,Nielsen.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding:LGFwasfundedbyanAustralianPostgraduateAwardfromtheDepartmentofIndustry,Innovation,Science,ResearchandTertiaryEducationofthe AustralianGovernment,and