学科分类
/ 2
28 个结果
  • 简介:Microarrayhasbecomeapopularbiotechnologyinbiologicalandmedicalresearch.However,systematicandstochasticvariabilitiesinmicroarraydataareexpectedandunavoidable,resultingintheproblemthattherawmeasurementshaveinherent"noise"withinmicroarrayexperiments.Currently,logarithmicratiosareusuallyanalyzedbyvariousclusteringmethodsdirectly,whichmayintroducebiasinterpretationinidentifyinggroupsofgenesorsamples.Inthispaper,astatisticalmethodbasedonmixedmodelapproacheswasproposedformicroarraydataclusteranalysis.TheunderlyingrationaleofthismethodistopartitiontheobservedtotalgeneexpressionlevelintovariousvariationscausedbydifferentfactorsusinganANOVAmodel,andtopredictthedifferentialeffectsofGV(genebyvariety)interactionusingtheadjustedunbiasedprediction(AUP)method.ThepredictedGVinteractioneffectscanthenbeusedastheinputsofclusteranalysis.Weillustratedtheapplicationofourmethodwithageneexpressiondatasetandelucidatedtheutilityofourapproachusinganexternalvalidation.

  • 标签: 聚类基因 基因表达 微分结构 互感作用 基因多样性
  • 简介:G-proteincoupledreceptors(GPCRs)representoneofthemostimportantclassesofdrugtargetsforpharmaceuticalindustryandplayimportantrolesincellularsignaltransduction.PredictingthecouplingspecificityofGPCRstoG-proteinsisvitalforfurtherunderstandingthemechanismofsignaltransductionandthefunctionofthereceptorswithinacell,whichcanprovidenewcluesforpharmaceuticalresearchanddevelopment.Inthisstudy,thefeaturesofaminoacidcompositionsandphysiochemicalpropertiesofthefull-lengthGPCRsequenceshavebeenanalyzedandextracted.Basedonthesefeatures,classifiershavebeendevelopedtopredictthecouplingspecificityofGPCRstoG-proteinsusingsupportvectormachines.Thetestingresultsshowthatthismethodcouldobtainbetterpredictionaccuracy.

  • 标签: G-蛋白 疾病预防 分子机制 临床表现
  • 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.

  • 标签: 生物信息学 基因组学 基因分析 基因解释系统
  • 简介:Thestudyofsmalldrugmoleculesinteractingwithnucleicacidsisanareaofintenseresearchthathasparticularrelevanceinourunderstandingofrelativemechanisminchemotherapeuticapplicationsandtheassociationbetweengenetics(includingsequencevariation)anddrugresponse.Inthiscontribution,wedemonstratehowthesequence-specificbindingofananticancerdrugDacarbazine(DTIC)tosinglebase(A-G)mismatchcouldbesensitivelydetectedbycombiningelectrochemicaldetectionwithbiosensingsurfacebasedongoldnanoparticles.

  • 标签: 电气化学 A-G基因 基因错配 抗癌药物 药物反应 纳米微粒
  • 简介:UnderstandingthecouplingspecificitybetweenGprotein-coupledreceptors(GPCRs)andspecificclassesofGproteinsisimportantforfurtherelucidationofreceptorfunctionswithinacell.IncreasinginformationonGPCRsequencesandtheGproteinfamilywouldfacilitatepredictionofthecouplingpropertiesofGPCRs.Inthisstudy,wedescribeanovelapproachforpredictingthecouplingspecificitybetweenGPCRsandGproteins.ThismethodusesnotonlyGPCRsequencesbutalsothefunctionalknowledgegeneratedbynaturallanguagepro-cessing,andcanachieve92.2%predictionaccuracybyusingtheC4.5algorithm.Furthermore,rulesrelatedtoGPCR-Gproteincouplingaregenerated.Thecom-binationofsequenceanalysisandtextminingimprovesthepredictionaccuracyforGPCR-Gproteincouplingspecificity,andalsoprovidescluesforunderstandingGPCRsignaling.

  • 标签: GPCR G蛋白 耦合特异性 预测 序列特征 生物机能
  • 简介:AcomputationalsystemforthepredictionandclassificationofhumanG-proteincoupledreceptors(GPCRs)hasbeendevelopedbasedonthesupportvectormachine(SVM)methodandproteinsequenceinformation.ThefeaturevectorsusedtodeveloptheSVMpredictionmodelsconsistofstatisticallysignificantfeaturesselectedfromsingleaminoacid,dipeptide,andtripeptidecompositionsofproteinsequences.Furthermore,thelengthdistributiondifferencebetweenGPCRsandnon-GPCRshasalsobeenexploitedtoimprovethepredictionperformance.ThetestingresultswithannotatedhumanproteinsequencesdemonstratethatthissystemcangetgoodperformanceforbothpredictionandclassificationofhumanGPCRs.

  • 标签: 疾病预防 识别方法 G-蛋白质 受体
  • 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.

  • 标签: G-蛋白 受体 遗传疾病 视紫红质
  • 简介:Nineshorttandemrepeat(STR)markersontheXchromosome(DXS101,DXS6789,DXS6799,DXS6804,DXS7132,DXS7133,DXS7423,DXS8378,andHPRTB)wereanalyzedinfourpopulationgroups(Mongol,Ewenki,Oroqen,andDaur)fromInnerMongolia,China,inordertolearnaboutthegeneticdiversity,forensicsuitability,andpossiblegeneticaffinitiesofthepopulations.Frequencyestimates,Hardy-Weinbergequilibrium,andotherparametersofforensicinterestwerecomputed.Theresultsrevealedthattheninemarkershaveamoderatede-greeofvariabilityinthepopulationgroups.Mostheterozygosityvaluesfortheninelocirangefrom0.480to0.891,andthereareevidentdifferencesofgeneticvariabilityamongthepopulations.AUPGMAtreeconstructedonthebasisofthegenerateddatashowsverylowgeneticdistancebetweentMongolandHan(Xi’an)populations.Ourresultsbasedongeneticdistanceanalysisareconsistentwiththeresultsofearlierstudiesbasedonlinguisticsandtheimmigrationhistoryandoriginofthesepopulations.TheminisatellitelociontheXchromosomestudiedherearenotonlyusefulinshowingsignificantgeneticvariationbetweenthepop-ulations,butalsoaresuitableforhumanidentitytestingamongInnerMongolianpopulations.

  • 标签: 中国人 内蒙古 遗传距离 遗传多态性 染色体
  • 简介:Thesurfaceglycoproteinhemagglutinin(HA)helpstheinfluenzaAvirustoevadethehostimmunesystembyantigenicvariationandisamajordrivingforceforviralevolution.Inthisstudy,theselectionpressureonHAofH5N1influenzaAviruswasanalyzedusingbioinformaticsalgorithms.Mostoftheidentifiedpositiveselection(PS)siteswerefoundtobewithinoradjacenttoepitopesites.SomeoftheidentifiedPSsitesareconsistentwithpreviousexperimentalstudies,providingfurthersupporttothebiologicalsignificanceofourfindings.ThehighestfrequencyofPSsiteswasobservedinrecentstrainsisolatedduring2005–2007.PhylogeneticanalysiswasalsoconductedonHAsequencesfromvarioushosts.Viraldriftisalmostsimilarinbothavianandhumanspecieswithaprogressivetrendovertheyears.OurstudyreportsnewmutationsinfunctionalregionsofHAthatmightprovidemarkersforvaccinedesignorcanbeusedtopredictisolatesofpandemicpotential.

  • 标签: H5N1病毒 选择压力 血凝素 演变 系统发育分析 流感病毒
  • 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.

  • 标签: G-蛋白相连受体 信号通道 转移因子 EGR-3
  • 简介:在染色体为特定的DNA目标设计锌手指蛋白质主题在染色体工程的领域里是批评的。我们为为绑在特定的目标DNA地点的C2H2锌手指预言识别helices开发了一个计算方法。这预言用锌手指蛋白质和他们的目标DNA三位字节的彻底的数据集基于人工的神经网络。用户们能为也要预言在的二或三根锌手指选择选择一模块化或为输入DNA顺序的synergistic时尚。这个方法将为对为几个生物、生物医学的应用程序设计特定的锌手指抄写因素和锌手指核酸酶感兴趣的研究人员是珍贵的。网工具ZiF预言在http://web.iitd.ac.in/sundar/zifpredict/在网上是可得到的。

  • 标签: C2H2型锌指蛋白 DNA序列 Web 结合特异性 预测 工具
  • 简介:骨头导出髓的间充质的干细胞(MSC)是为房间移植在临床的应用程序显示出一个重要潜力的pluripotent干细胞。在现在的论文,proteomic技术被用来接近与猪的骨头髓MSC联系的蛋白质侧面并且在5-azacytidine(5-aza)的效果上调查MSC蛋白质的规定。超过1,700蛋白质种类根据胶化分析与MSC被分开。与控制MSC介绍的表达式相比,有起来调整的11个蛋白质点并且26在5-aza-treated房间的蛋白质模式下面调整。21蛋白质的一个总数被MALDI-TOF-MS分析成功地识别,在哪个之中一些有趣的蛋白质,例如高山哈B-crystallin,在A2的附属建筑,和stathmin1,被报导了通过不同发信号的小径在房间增长和区别包含。我们的数据应该为MSC区别和apoptosis的未来学习是有用的。

  • 标签: 5-氮胞苷 基因表达 骨髓干细胞 电泳实验
  • 简介:Humantumornecrosisfactorα(hTNFα),apleiotropiccytokinewithactivitiesrangingfromhostdefensemechanismsininfectionandinjurytoseveretoxicityinsepticshockorotherrelateddiseases,isapromisingtargetfordrugscreening.UsingtheSELEX(systematicevolutionofligandsbyexponentialenrichment)process,weisolatedoligonucleotideligands(aptamers)withhighaffinitiesforhTNFα.Aptamerswereselectedfromastartingpoolof40randomizedsequencescomposedofabout1015RNAmolecules.RepresentativeaptamersweretruncatedtotheminimallengthwithhighaffinityforhTNFαandwerefurthermodifiedbyreplacementof2'-OHwith2'-Fand2'-NH2atallribopurinepositions.ThesemodifiedRNAaptamerswereresistanttonuclease.ThespecificityoftheseaptamersforhTNFαwasconfirmed,andtheiractivitytoinhibitthecytotoxicityofhTNFαonmouseL929cellswasdetermined.Resultsdemonstratedthatfour2'-NH2-modifiedaptamersboundtohTNFαwithhighaffinityandblockedthebindingofhTNFαtoitsreceptor,thusprotectingtheL929cellsfromthecytotoxicityofhTNFα.OligonucleotideaptamersdescribedherearepotentialtherapeuticsanddiagnosticsforhTNFc-relateddiseases.

  • 标签: HTNFΑ 人肿瘤坏死因子Α 相似法则 RNA 核糖核酸 低聚核苷酸配位子
  • 简介:Domaindatabaseisessentialfordomainpropertyresearch.Eliminatingredundantinformationindatabasequeryisveryimportantfordatabasequality.Herewereportthemanualconstructionofanon-redundanthumanSH2domaindatabase.Thereare119humanSH2domainsin110SH2-containingproteins.HumanSH2swerealignedwithClustalX,andahomologoustreewasgenerated.Inthistree,proteinswithsimilarknownfunctionwereclassifiedintothesamegroup.Someproteinsinthesamegrouphavebeenreportedtohavesimilarbindingmotifsexperimentally.Thetreemightprovidecluesaboutpossiblefunctionsofhypotheticalproteinsforfurtherexperimentalverification.

  • 标签: 人类基因组计划 SH2域 同源性 系统进化树 非冗余数据库
  • 简介:Inthepost-genomicera,variouscomputationalmethodsthatpredictprotein-proteininteractionsatthegenomelevelareavailable;however,eachmethodhasitsownadvantagesanddisadvantages,resultinginfalsepredictions.Herewedevel-opedauniqueintegratedapproachtoidentifyinteractingpartner(s)ofSemaphorin5A(SEMA5A),beginningwithsevenproteinssharingsimilarligandinteractingresiduesasputativebindingpartners.ThemethodsincludeDwyerandRoot-Bernstein/Dillontheoriesofproteinevolution,hydropathiccomplementarityofproteinstructure,patternofproteinfunctionsamongmolecules,informationondomain-domaininteractions,co-expressionofgenesandproteinevolution.AmongthesetofsevenproteinsselectedasputativeSEMA5Ainteractingpartners,wefoundthefunctionsofPlexinB3andNeuropilin-2tobeassociatedwithSEMA5A.WemodeledthesemaphorindomainstructureofPlexinB3andfoundthatitsharessimilaritywithSEMA5A.Moreover,avirtualexpressiondatabasesearchandRT-PCRanalysisshowedco-expressionofSEMA5AandPlexinB3andtheseproteinswerefoundtohaveco-evolved.Inaddition,weconfirmedtheinterac-tionofSEMA5AwithPlexinB3inco-immunoprecipitationstudies.Overall,thesestudiesdemonstratethatanintegratedmethodofpredictioncanbeusedatthegenomelevelfordiscoveringmanyunknownproteinbindingpartnerswithknownligandbindingdomains.

  • 标签: 蛋白质结构 相关蛋白 相互作用 APRIORI 互补 后基因组时代
  • 简介:以便获得米饭幼仔圆锥花序proteome的高分辨率的electrophorogram,我们评估了通常使用在的各种各样的协议二维(2D)蛋白质的polyacrylamide胶化电气泳动(页)包括染色协议的胶化,使不能调动的pH坡度(IPG)的pH范围脱衣并且样品装载数量。结果证明染色协议使用的银敏化包含冰川的醋酸,钠醋酸盐和钠thiosulfate的答案(在1988由Heukeshoven和Dernick报导了)并且染色方法使用答案包含的Coomassie灿烂的蓝色G-250,铵硫酸盐和磷的酸(在2010由粉红色的等报导了)表明了优异染色效果。另外,当有5-8的pH范围的IPG胶化长带被使用时,我们也与4-7的pH范围证明更高的分辨率被完成,与那相比。最后,最佳的装载数量作为与染色协议的银硝酸盐在联合与pH5-8使用17厘米长的非线性的IPG长带的130g被决定。评估结果将在年轻米饭颖果的proteome分析是有用的。

  • 标签: 聚丙烯酰胺凝胶电泳 蛋白质组分 协议 水稻 评价 颖果