Functional Characterization of Transcription Factor Motifs Using Cross-species Comparison across Large Evolutionary Distances 英文参考文献.docVIP

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Functional Characterization of Transcription Factor Motifs Using Cross-species Comparison across Large Evolutionary Distances 英文参考文献.doc

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Functional Characterization of Transcription Factor Motifs Using Cross-species Comparison across Large Evolutionary Distances 英文参考文献

FunctionalCharacterizationofTranscriptionFactor MotifsUsingCross-speciesComparisonacrossLarge EvolutionaryDistances JaebumKim1,RyanCunningham1,BrianJames1,StefanWyder2,JoshuaD.Gibson3,OliverNiehuis4, EvgenyM.Zdobnov2,HughM.Robertson5,6,GeneE.Robinson5,6,JohnH.Werren7,SaurabhSinha1,6* 1Department of Computer Science, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America, 2Department of Genetic Medicine and Development,UniversityofGenevaMedicalSchool,andSwissInstituteofBioinformatics,Geneva,Switzerland,3SchoolofLifeSciences,ArizonaStateUniversity,Tempe, Arizona,UnitedStatesofAmerica,4DepartmentofBiology,UniversityofOsnabru¨ck,Osnabru¨ck,Germany,5DepartmentofEntomology,UniversityofIllinoisatUrbana- Champaign, Urbana, Illinois, United States of America, 6Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, United States of America,7DepartmentofBiology,UniversityofRochester,Rochester,NewYork,UnitedStatesofAmerica Abstract Weaddresstheproblemoffindingstatisticallysignificantassociationsbetweencis-regulatorymotifsandfunctionalgene sets,inordertounderstandthebiologicalrolesoftranscriptionfactors.Wedevelopacomputationalframeworkforthis task,whosefeaturesincludeanewstatisticalscoreformotifscanning,theuseofdifferentscoresforpredictingtargetsof differentmotifs,andnewwaystodealwithredundanciesamongsignificantmotif–functionassociations.Thisframeworkis appliedtotherecentlysequencedgenomeofthejewelwasp,Nasoniavitripennis,makinguseoftheexistingknowledgeof motifsandgeneannotationsinanotherinsectgenome,thatofthefruitfly.Theframeworkusescross-speciescomparisonto improvethespecificityofitspredictions,anddoessowithoutrelyinguponnon-codingsequencealignment.Itistherefore wellsuitedforcomparativegenomicsacrosslargeevolutionarydivergences,whereexistingalignment-basedmethodsare notapplicable.Wealsoapplytheframeworktofindmotifsassociatedwithsociallyregulatedgenesetsinthehoneybee, Apismellifera,usingcomparisonswithNasoni