Ontology-Based Meta-Analysis of Global Collections of High-Throughput Public Data 英文参考文献.docVIP

Ontology-BasedMeta-AnalysisofGlobalCollectionsof High-ThroughputPublicData IlyaKupershmidt1,2*,QiaojuanJaneSu1,AnoopGrewal1,SumanSundaresh1,InbalHalperin1 ,James Flynn1,MamathaShekar1,HelenWang1,JennyPark1,WenwuCui1,GregoryD.Wall1,RobertWisotzkey1, SatnamAlag1,SaeidAkhtari1,MostafaRonaghi1,3 1NextBio,Cupertino,California,UnitedStatesofAmerica,2RoyalInstituteofTechnology(KTH),Stockholm,Sweden,3Illumina,SanDiego,California,UnitedStatesof America Abstract Background:Theinvestigationoftheinterconnectionsbetweenthemolecularandgeneticeventsthatgovernbiological systemsisessentialifwearetounderstandthedevelopmentofdiseaseanddesigneffectivenoveltreatments.Microarray and next-generation sequencing technologies have the potential to provide this information. However, taking full advantage of these approaches requires that biological connections be made across large quantities of highly heterogeneous genomic datasets. Leveraging the increasingly huge quantities of genomic data in the public domain is fastbecomingoneofthekeychallengesintheresearchcommunitytoday. Methodology/Results: Wehavedevelopedanoveldataminingframeworkthatenablesresearcherstousethisgrowing collectionofpublichigh-throughputdatatoinvestigateanysetofgenesorproteins.Theconnectivitybetweenmolecular statesacrossthousandsofheterogeneousdatasetsfrommicroarraysandothergenomicplatformsisdeterminedthrougha combination of rank-based enrichment statistics, meta-analyses, and biomedical ontologies. We address data quality concerns through dataset replication and meta-analysis and ensure that the majority of the findings are derived using multiple lines of evidence. As an example of our strategy and the utility of this framework, we apply our data mining approachtoexplorethebiologyofbrownfatwithinthecontextofthethousandsofpubliclyavailablegeneexpression datasets. Conclusions:Ourworkpresentsapracticalstrategyfororganizing,mining,andcorrelatingglobalcollectionsoflarge-scale genomicdatatoexplorenormalanddiseasebiology.Usi