Signalogs Orthology-Based Identification of Novel Signaling Pathway Components in Three Metazoans 英文参考文献.docVIP

Signalogs:Orthology-BasedIdentificationofNovel SignalingPathwayComponentsinThreeMetazoans Tama′sKorcsma′ros1,2.,Ma′te′ S.Szalay2.,PetraRovo′1,RobinPalotai2,Da′vidFazekas1,KatalinLenti3, Ille′sJ.Farkas4,Pe′terCsermely2,TiborVellai1* 1Department of Genetics, Eo¨tvo¨s Lora′nd University, Budapest, Hungary, 2Department of Medical Chemistry, Faculty of Medicine, Semmelweis University, Budapest, Hungary, 3Department of Morphology and Physiology, Faculty of Health Sciences, Semmelweis University, Budapest, Hungary, 4Statistical and Biological Physics ResearchGroupoftheHungarianAcademyofSciencesandEo¨tvo¨sUniversity,Budapest,Hungary Abstract Background: Uncovering novel components of signal transduction pathways and their interactions within species is a central task in current biological research. Orthology alignment and functional genomics approaches allow the effective identification of signaling proteins by cross-species data integration. Recently, functional annotation of orthologs was transferred across organisms to predict novel roles for proteins. Despite the wide use of these methods, annotation of completesignalingpathwayshasnotyetbeentransferredsystematicallybetweenspecies. PrincipalFindings:Hereweintroducetheconceptof‘signalog’todescribepotentialnovelsignalingfunctionofaprotein on the basis of the known signaling role(s) of its ortholog(s). To identify signalogs on genomic scale, we systematically transferredsignalingpathwayannotationsamongthreeanimalspecies,thenematodeCaenorhabditiselegans,thefruitfly Drosophilamelanogaster,andhumans.UsingorthologydatafromInParanoidandsignalingpathwayinformationfromthe SignaLinkdatabase,wepredict88worm,92fly,and73humannovelsignalingcomponents.Furthermore,wedevelopedan on-linetoolandaninteractiveorthologynetworkviewertoallowuserstopredictandvisualizecomponentsoforthologous pathways. We verified the novelty of the predicted signalogs by literature search and comparison to known pathway annotations. In C. elegans, 6 out of the