A Survey of Genomic Properties for the Detection of Regulatory Polymorphisms 英文参考文献.docVIP

ASurveyofGenomicProperties fortheDetectionofRegulatoryPolymorphisms Stephen B.Montgomery¤*,Obi L.Griffith, Johanna M. Schuetz, Angela Brooks-Wilson, Steven J.M.Jones Canada’sMichaelSmithGenomeSciencesCentre,BritishColumbiaCancerAgency,Vancouver,BritishColumbia,Canada Advances in the computational identification of functional noncoding polymorphisms will aid in cataloging novel determinants of health and identifying genetic variants that explain human evolution. To date, however, the development and evaluation of such techniques has been limited by the availability of known regulatory polymorphisms. We have attempted to address this by assembling, from the literature, a computationally tractable setofregulatorypolymorphismswithintheORegAnnodatabase().Wehavefurtherused104 regulatorysingle-nucleotidepolymorphismsfromthissetand951polymorphismsofunknownfunction,from2-kband 152-bpnoncodingupstreamregionsofgenes,toinvestigatethediscriminatorypotentialof23propertiesrelatedto generegulationandpopulationgenetics.Amongthemostimportantpropertiesdetectedinthisregionaredistanceto transcription start site, local repetitive content, sequence conservation, minor and derived allele frequencies, and presence of a CpG island. We further used the entire set of properties to evaluate their collective performance in detectingregulatorypolymorphisms.Usinga10-foldcross-validationapproach,wewereabletoachieveasensitivity andspecificityof0.82and0.71,respectively,andweshowthatthisperformanceisstronglyinfluencedbythedistance tothetranscriptionstartsite. Citation:MontgomerySB,GriffithOL,SchuetzJM,Brooks-WilsonA,JonesSJM(2007)Asurveyofgenomicpropertiesforthedetectionofregulatorypolymorphisms.PLoS ComputBiol3(6):e106.doi:10.1371/journal.pcbi.0030106 expressionofgenes.SuchrSNPshavebeenimplicatedinthe etiology of several human diseases, including cancer [17,18], Introduction Our ability to identify the molecular mechanisms respon- sibleforspeci?cgenetictraitswithinourpopulationwillbe enhancedbyo