Random Phenotypic Variation of Yeast (Saccharomyces cerevisiae) Single-Gene Knockouts Fits a Double Pareto-Lognormal Distribution 英文参考文献.docVIP

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Random Phenotypic Variation of Yeast (Saccharomyces cerevisiae) Single-Gene Knockouts Fits a Double Pareto-Lognormal Distribution 英文参考文献.doc

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Random Phenotypic Variation of Yeast (Saccharomyces cerevisiae) Single-Gene Knockouts Fits a Double Pareto-Lognormal Distribution 英文参考文献

RandomPhenotypicVariationofYeast(Saccharomyces cerevisiae)Single-GeneKnockoutsFitsaDoublePareto- LognormalDistribution JohnH.Graham1*,DanielT.Robb2,3,AmyR.Poe1,4 1DepartmentofBiology,BerryCollege,MountBerry,Georgia,UnitedStatesofAmerica,2DepartmentofPhysics,Astronomy,andGeology,BerryCollege,MountBerry, Georgia,UnitedStatesofAmerica,3DepartmentofMathematics,ComputerScienceandPhysics,RoanokeCollege,Salem,Virginia,UnitedStatesofAmerica,4Centerfor IntegrativeGenomics,GeorgiaInstituteofTechnology,Atlanta,Georgia,UnitedStatesofAmerica Abstract Background: Distributed robustness is thought to influence the buffering of random phenotypic variation through the scale-freetopologyofgeneregulatory,metabolic,andprotein-proteininteractionnetworks.Ifthishypothesisistrue,then thephenotypicresponsetotheperturbationofparticularnodesinsuchanetworkshouldbeproportionaltothenumberof linksthosenodesmakewithneighboringnodes.Thissuggestsaprobabilitydistributionapproximatinganinversepower- law of random phenotypic variation. Zero phenotypic variation, however, is impossible, because random molecular and cellularprocessesareessentialtonormaldevelopment.Consequently,amorerealisticdistributionshouldhaveay-intercept closetozerointhelowertail,amodegreaterthanzero,andalong(fat)uppertail.ThedoublePareto-lognormal(DPLN) distributionisanidealcandidatedistribution.Itconsistsofamixtureofalognormalbodyandupperandlowerpower-law tails. Objective and Methods: If our assumptions are true, the DPLN distribution should provide a better fit to random phenotypicvariationinalargeseriesofsingle-geneknockoutlinesthanotherskewedorsymmetricaldistributions.Wefita large published data set of single-gene knockout lines in Saccharomyces cerevisiae to seven different probability distributions: DPLN, right Pareto-lognormal (RPLN), left Pareto-lognormal (LPLN), normal, lognormal, exponential, and Pareto.ThebestmodelwasjudgedbytheAkaikeInformationCriterion(AIC). Results: Phenotypic variation among gene knockouts in S. cer