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Efficient Reverse-Engineering of a Developmental Gene Regulatory Network 英文参考文献.docVIP

Efficient Reverse-Engineering of a Developmental Gene Regulatory Network 英文参考文献.doc

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Efficient Reverse-Engineering of a Developmental Gene Regulatory Network 英文参考文献

EfficientReverse-EngineeringofaDevelopmentalGene RegulatoryNetwork AntonCrombach1.,KarlR.Wotton1.,DamjanCicin-Sain1,MaksatAshyraliyev2,JohannesJaeger1* 1EMBL/CRGResearchUnitinSystemsBiology,CentreforGenomicRegulation(CRG)andUniversitatPompeuFabra(UPF),Barcelona,Spain,2DepartmentofMathematics andComputerSciences,Bahc?es?ehir University,Istanbul,Turkey Abstract Understanding the complex regulatory networks underlying development and evolution of multi-cellular organisms is a majorprobleminbiology.Computationalmodelscanbeusedastoolstoextracttheregulatorystructureanddynamicsof suchnetworksfromgeneexpressiondata.Thisapproachiscalledreverseengineering.Ithasbeensuccessfullyappliedto many gene networks in various biological systems. However, to reconstitute the structure and non-linear dynamics of a developmentalgenenetworkinitsspatialcontextremainsaconsiderablechallenge.Here,weaddressthischallengeusing a case study: the gap gene network involved in segment determination during early development of Drosophila melanogaster. A major problem for reverse-engineering pattern-forming networks is the significant amount of time and effort required to acquire and quantify spatial gene expression data. We have developed a simplified data processing pipelinethatconsiderablyincreasesthethroughputofthemethod,butresultsindataofreducedaccuracycomparedto thosepreviously used for gapgene network inference. Wedemonstrate that wecaninfer the correct networkstructure usingourreduceddataset,andinvestigateminimaldatarequirementsforsuccessfulreverseengineering.Ourresultsshow that timing and position of expression domain boundaries are the crucial features for determining regulatory network structurefromdata,whileitislessimportanttopreciselymeasureexpressionlevels.Basedonthis,wedefineminimaldata requirements for gap gene network inference. Our results demonstrate the feasibility of reverse-engineering with much reduced experimental effort. This enables more widespread use of the method in differ

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