OrthoList A Compendium of C. elegans Genes with Human Orthologs 英文参考文献.docVIP

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OrthoList A Compendium of C. elegans Genes with Human Orthologs 英文参考文献.doc

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OrthoList A Compendium of C. elegans Genes with Human Orthologs 英文参考文献

OrthoList:ACompendiumofC.elegansGeneswith HumanOrthologs DanielD.Shaye1*,IvaGreenwald1,2,3* 1Howard Hughes Medical Institute, Columbia University, College of Physicians and Surgeons, New York, New York, United States of America, 2Department of Biochemistry and Molecular Biophysics, Columbia University, College of Physicians and Surgeons, New York, New York, United States of America, 3Department of GeneticsandDevelopment,ColumbiaUniversity,CollegeofPhysiciansandSurgeons,NewYork,NewYork,UnitedStatesofAmerica Abstract Background:C.elegansisanimportantmodelforgeneticstudiesrelevanttohumanbiologyanddisease.Wesoughtto assesstheorthologybetweenC.elegansandhumangenestounderstandbettertherelationshipbetweentheirgenomes andtogenerateacompellinglistofcandidatestostreamlineRNAi-basedscreensinthismodel. Results:Weperformedameta-analysisofresultsfromfourorthologypredictionprogramsandgeneratedacompendium, ‘‘OrthoList’’, containing 7,663 C. elegans protein-coding genes. Various assessments indicate that OrthoList has extensive coveragewithlowfalse-positiveandfalse-negativerates.Partofthisevaluationexaminedtheconservationofcomponents of the receptor tyrosine kinase, Notch, Wnt, TGF-? and insulin signaling pathways, and led us to update compendia of conservedC.eleganskinases,nuclearhormonereceptors,F-boxproteins,andtranscriptionfactors.Comparisonwithtwo publishedgenome-wideRNAiscreensindicatedthatvirtuallyalloftheconservedhitswouldhavebeenobtainedhadjust theOrthoListset(,38%ofthegenome)beentargeted.WecompiledOrtholistbyInterProdomainsandGeneOntology annotation,makingiteasytoidentifyC.elegansorthologsofhumandiseasegenesforpotentialfunctionalanalysis. Conclusions: We anticipate that OrthoList will be of considerable utility to C. elegans researchers for streamlining RNAi screens,byfocusingongeneswithapparenthumanorthologs,thusreducingscreeningeffortby,60%.Moreover,wefind thatOrthoListprovidesausefulbasisforannotatingorthologyandrevealsmoreC.elegansorthologsofhumangenesin variousfunct