Process-Driven Inference of Biological Network Structure Feasibility, Minimality, and Multiplicity 英文参考文献.docVIP

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Process-Driven Inference of Biological Network Structure Feasibility, Minimality, and Multiplicity 英文参考文献.doc

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Process-Driven Inference of Biological Network Structure Feasibility, Minimality, and Multiplicity 英文参考文献

Process-DrivenInferenceofBiologicalNetwork Structure:Feasibility,Minimality,andMultiplicity GuanyuWang1,YongwuRong2,HaoChen1,CarlPearson1,ChenghangDu1,RahulSimha3,ChenZeng1,4* 1Department of Physics, George Washington University, Washington, D.C., United States of America, 2Department of Mathematics, George Washington University, Washington, D.C., United States of America, 3Department of Computer Science, George Washington University, Washington, D.C., United States of America, 4DepartmentofPhysics,HuazhongUniversityofScienceandTechnology,Wuhan,China Abstract Acommonprobleminmolecularbiologyistouseexperimentaldata,suchasmicroarraydata,toinferknowledgeaboutthe structure of interactions between important molecules in subsystems of the cell. By approximating the state of each moleculeas‘‘on’’or‘‘off’’,itbecomespossibletosimplifytheproblem,andexploitthetoolsofBooleananalysisforsuch inference.AmongstBooleantechniques,theprocess-drivenapproachhasshownpromiseinbeingabletoidentifyputative networkstructures,aswellasstabilityandmodularityproperties.Thispaperexaminestheprocess-drivenapproachmore formally,andmakesfourcontributionsaboutthecomputationalcomplexityoftheinferenceproblem,underthe‘‘dominant inhibition’’assumptionofmolecularinteractions.Thefirstisaproofthatthefeasibilityproblem(doesthereexistanetwork thatexplainsthedata?)canbesolvedinpolynomial-time.Second,theminimalityproblem(whatisthesmallestnetwork thatexplainsthedata?)isshowntobeNP-hard,andthereforeunlikelytoresultinapolynomial-timealgorithm.Third,a simplepolynomial-timeheuristicisshowntoproducenear-minimalsolutions,asdemonstratedbysimulation.Fourth,the theoretical framework explains how multiplicity (the number of network solutions to realize a given biological process), whichcantakeexponential-timetocompute,caninsteadbeaccuratelyestimatedbyafast,polynomial-timeheuristic. Citation: Wang G, Rong Y, Chen H, Pearson C, Du C, et al. (2012) Process-Driven Inference of Biological Network Structure: Feasibility, Minima