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

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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.

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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.

简介：一个新奇高产量的系统，为分离和反应(4SR)叫了叠的片胶化系统，为DNA/RNA和蛋白质/肽的分析被开发。系统提供利用叠的片胶化的性质的一条新奇三维的胶化电气泳动途径。它同时允许多重样品反应以及被分开，出现一二维(mxn)样品装载系统。为这个目的，包含井(在这篇论文的100口井)的可变数字的高产量的多微的容器(MMV)被使用了，它用25公里做的是方形尺寸的polyacrylamide胶化。在electrophoretic分离以后，而且，包含一件需要的样品的片胶化能容易被移开并且继续到下一步。不同生物反应以及产品的连续分离有效地被执行处理DNA/RNA和蛋白质/肽。它证明这个系统有多种潜力被发展。

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