Gene Regulatory Networks from Multifactorial Perturbations Using Graphical Lasso Application to the DREAM4 Challenge 英文参考文献.docVIP

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Gene Regulatory Networks from Multifactorial Perturbations Using Graphical Lasso Application to the DREAM4 Challenge 英文参考文献.doc

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Gene Regulatory Networks from Multifactorial Perturbations Using Graphical Lasso Application to the DREAM4 Challenge 英文参考文献

GeneRegulatoryNetworksfromMultifactorial PerturbationsUsingGraphicalLasso:Applicationtothe DREAM4Challenge PatriciaMene′ndez1,2,YiannisA.I.Kourmpetis1,3,CajoJ.F.terBraak1*,FredA.vanEeuwijk1,2 1Biometris, Wageningen University, Wageningen, The Netherlands, 2Centre for BioSystems Genetics, Wageningen, The Netherlands, 3Laboratory of Bioinformatics, WageningenUniversity,Wageningen,TheNetherlands Abstract Amajorchallengeinthefieldofsystemsbiologyconsistsofpredictinggeneregulatorynetworksbasedondifferenttraining data.WithintheDREAM4initiative,wetookpartinthemultifactorialsub-challengethataimedtopredictgeneregulatory networksofsize100fromtrainingdataconsistingofsteady-statelevelsobtainedafterapplyingmultifactorialperturbations totheoriginalinsiliconetwork. Duetothestaticcharacterofthechallengedata,wetackledtheproblemviaasparse Gaussian Markov Random Field, which relates network topology with the covariance inverse generated by the gene measurements.Asforthecomputations,weusedtheGraphicalLassoalgorithmwhichprovidedalargerangeofcandidate network topologies. The main task was to select the optimal network topology and for that, different model selection criteriawereexplored.Theselectednetworkswerecomparedwiththegoldenstandardsandtheresultsrankedusingthe scoring metrics applied in the challenge, giving a better insight in our submission and the way to improve it. Our approachprovidesaneasystatisticalandcomputationalframeworktoinfergeneregulatorynetworksthatissuitablefor largenetworks,evenifthenumberoftheobservations(perturbations)isgreaterthanthenumberofvariables(genes). Citation:Mene′ndez P,KourmpetisYAI,terBraakCJF,vanEeuwijkFA(2010)GeneRegulatoryNetworksfromMultifactorialPerturbationsUsingGraphicalLasso: ApplicationtotheDREAM4Challenge.PLoSONE5(12):e14147.doi:10.1371/journal.pone.0014147 Editor:MarkIsalan,CenterforGenomicRegulation,Spain ReceivedMarch30,2010;AcceptedNovember8,2010;PublishedDecember20,2010 Copyright: ?2010 Menendez et al. This is an open-access article