简介：G-proteincoupledreceptors(GPCRs)representoneofthemostimportantclassesofdrugtargetsforpharmaceuticalindustryandplayimportantrolesincellularsignaltransduction.PredictingthecouplingspecificityofGPCRstoG-proteinsisvitalforfurtherunderstandingthemechanismofsignaltransductionandthefunctionofthereceptorswithinacell,whichcanprovidenewcluesforpharmaceuticalresearchanddevelopment.Inthisstudy,thefeaturesofaminoacidcompositionsandphysiochemicalpropertiesofthefull-lengthGPCRsequenceshavebeenanalyzedandextracted.Basedonthesefeatures,classifiershavebeendevelopedtopredictthecouplingspecificityofGPCRstoG-proteinsusingsupportvectormachines.Thetestingresultsshowthatthismethodcouldobtainbetterpredictionaccuracy.

简介：Allelefrequenciesfor15shorttandemrepeat(STR)loci(D8S1179,D21S11,D7S820,CSF1PO,D3S1358,TH01,D13S317,D16S539,D2S1338,D19S433,vWA,TPOX,D18S51,D5S818,andFGA)wereobtainedfrom7,636unrelatedindivid-ualsofChineseHanpopulationlivinginQinghaiandChongqing,China.Totally206alleleswereobserved,withthecorrespondingallelefrequenciesrangingfrom0.0001–0.4982.Chi-squaretestshowedthatalloftheSTRlociagreedwiththeHardy-Weinbergequilibrium.Wealsocomparedourdatawithpreviouslypub-lishedpopulationdataofotherethnicsorareas.TheresultsarevaluableforhumanidentificationandpaternitytestinginChineseHanpopulation.

简介：Microarrayhasbecomeapopularbiotechnologyinbiologicalandmedicalresearch.However,systematicandstochasticvariabilitiesinmicroarraydataareexpectedandunavoidable,resultingintheproblemthattherawmeasurementshaveinherent"noise"withinmicroarrayexperiments.Currently,logarithmicratiosareusuallyanalyzedbyvariousclusteringmethodsdirectly,whichmayintroducebiasinterpretationinidentifyinggroupsofgenesorsamples.Inthispaper,astatisticalmethodbasedonmixedmodelapproacheswasproposedformicroarraydataclusteranalysis.TheunderlyingrationaleofthismethodistopartitiontheobservedtotalgeneexpressionlevelintovariousvariationscausedbydifferentfactorsusinganANOVAmodel,andtopredictthedifferentialeffectsofGV(genebyvariety)interactionusingtheadjustedunbiasedprediction(AUP)method.ThepredictedGVinteractioneffectscanthenbeusedastheinputsofclusteranalysis.Weillustratedtheapplicationofourmethodwithageneexpressiondatasetandelucidatedtheutilityofourapproachusinganexternalvalidation.

简介：Annotationsofcompletegenomesequencessubmitteddirectlyfromsequencingprojectsarediverseintermsofannotationstrategiesandupdatefrequencies.Theseinconsistenciesmakecomparativestudiesdifficult.Toallowrapiddataprepara-tionofalargenumberofcompletegenomes,automationandspeedareimpor-tantforgenomere-annotation.Hereweintroduceanopen-sourcerapidgenomere-annotationsoftwaresystem,Restauro-G,specializedforbacterialgenomes.Restauro-Gre-annotatesagenomebysimilaritysearchesutilizingtheBLAST-LikeAlignmentTool,referringtoproteindatabasessuchasUniProtKB,NCBInr,NCBICOGs,Pfam,andPSORTb.Re-annotationbyRestauro-Gachievedover98%accuracyformostbacterialchromosomesincomparisonwiththeoriginalmanuallycuratedannotationofEMBLreleases.Restauro-GwasdevelopedinthegenericbioinformaticsworkbenchG-languageGenomeAnalysisEnvironmentandisdistributedathttp://restauro-g.iab.keio.ac.jp/undertheGNUGeneralPublicLicense.

简介：Thestudyofsmalldrugmoleculesinteractingwithnucleicacidsisanareaofintenseresearchthathasparticularrelevanceinourunderstandingofrelativemechanisminchemotherapeuticapplicationsandtheassociationbetweengenetics(includingsequencevariation)anddrugresponse.Inthiscontribution,wedemonstratehowthesequence-specificbindingofananticancerdrugDacarbazine(DTIC)tosinglebase(A-G)mismatchcouldbesensitivelydetectedbycombiningelectrochemicaldetectionwithbiosensingsurfacebasedongoldnanoparticles.

简介：UnderstandingthecouplingspecificitybetweenGprotein-coupledreceptors(GPCRs)andspecificclassesofGproteinsisimportantforfurtherelucidationofreceptorfunctionswithinacell.IncreasinginformationonGPCRsequencesandtheGproteinfamilywouldfacilitatepredictionofthecouplingpropertiesofGPCRs.Inthisstudy,wedescribeanovelapproachforpredictingthecouplingspecificitybetweenGPCRsandGproteins.ThismethodusesnotonlyGPCRsequencesbutalsothefunctionalknowledgegeneratedbynaturallanguagepro-cessing,andcanachieve92.2%predictionaccuracybyusingtheC4.5algorithm.Furthermore,rulesrelatedtoGPCR-Gproteincouplingaregenerated.Thecom-binationofsequenceanalysisandtextminingimprovesthepredictionaccuracyforGPCR-Gproteincouplingspecificity,andalsoprovidescluesforunderstandingGPCRsignaling.

简介：AcomputationalsystemforthepredictionandclassificationofhumanG-proteincoupledreceptors(GPCRs)hasbeendevelopedbasedonthesupportvectormachine(SVM)methodandproteinsequenceinformation.ThefeaturevectorsusedtodeveloptheSVMpredictionmodelsconsistofstatisticallysignificantfeaturesselectedfromsingleaminoacid,dipeptide,andtripeptidecompositionsofproteinsequences.Furthermore,thelengthdistributiondifferencebetweenGPCRsandnon-GPCRshasalsobeenexploitedtoimprovethepredictionperformance.ThetestingresultswithannotatedhumanproteinsequencesdemonstratethatthissystemcangetgoodperformanceforbothpredictionandclassificationofhumanGPCRs.

简介：G-proteincoupledreceptors(GPCRs)areaclassofseven-helixtransmembraneproteinsthathavebeenusedinbioinformaticsasthetargetstofacilitatedrugdiscoveryforhumandiseases.AlthoughthousandsofGPCRsequenceshavebeencollected,theligandspecificityofmanyGPCRsisstillunknownandonlyonecrystalstructureoftherhodopsin-likefamilyhasbeensolved.Therefore,identifyingGPCRtypesonlyfromsequencedatahasbecomeanimportantresearchissue.Inthisstudy,anoveltechniqueforidentifyingGPCRtypesbasedontheweightedLevenshteindistancebetweentworeceptorsequencesandthenearestneighbormethod(NNM)isintroduced,whichcandealwithreceptorsequenceswithdifferentlengthsdirectly.Inourexperimentsforclassifyingfourclasses(acetylcholine,adrenoceptor,dopamine,andserotonin)oftherhodopsin-likefamilyofGPCRs,theerrorratesfromtheleave-one-outprocedureandtheleave-half-outprocedurewere0.62%and1.24%,respectively.Theseresultsarepriortothoseofthecovariantdiscriminantalgorithm,thesupportvectormachinemethod,andtheNNMwithEuclideandistance.

简介：Werecentlyreportedtheuseofagene-trappingapproachtoisolatecellclonesinwhichareportergenehadintegratedintogenesmodulatedbyT-cellactivation.WehavenowtestedapanelofclonesfromthatreportandidentifiedtheonethatrespondstoavarietyofG-proteincoupledreceptors(GPCR).TheβlactamasetaggedEGR-3JurkatcellwasusedtodissectspecificGPCRsignalinginvivo.ThreeGPCRswerestudied,includingthechemokinereceptorCXCR4(Gicoupled)thatwasendogenouslyexpressed,theplateletactivationfactor(PAF)receptor(Gq-coupled),andβ2adrenergicreceptor(Gs-coupled)thatwasbothstablytransfected.Agonistsforeachreceptoractivatedtranscriptionoftheβ-lactamasetaggedEGR-3gene.InductionofEGR-3throughCXCR4wasblockedbypertussistoxinandPD58059,aspecificinhibitorofMEK(MAPK/ERKkinase).NeitheroftheseinhibitorsblockedisoproterenolorPAF-mediatedactivationofEGR-3.Conversely,β2-andPAF-mediatedEGR-3activationwasblockedbythep38,specificinhibitorSB580.Inaddition,bothβ2-andPAF-mediatedEGR-3activationcouldbesynergisticallyactivatedbyCXCR4activation.ThiscombinedresultindicatesthatEGR-3canbeactivatedthroughdistinctsignaltransductionpathwaysbydifferentGPCRsandthatsignalscanbeintegratedandamplifiedtoefficientlytunethelevelofactivation.