简介:Protein-proteininteractions(PPIs)havebeenwidelystudiedtounderstandthebiologicalprocessesormolecularfunctionsassociatedwithdifferentdiseasesystemslikecancer.Whilefocusedstudiesonindividualcancershavegeneratedvaluableinformation,globalandcomparativeanalysisofdatasetsfromdifferentcancertypeshasnotbeendone.Inthiswork,wecarriedoutbioinformaticanalysisofPPIscorrespondingtodifferentiallyexpressedgenesfrommicroarraysofvarioustumortissues(belongingtobladder,colon,kidneyandthyroidcancers)andcomparedtheirassociatedbiologicalprocessesandmolecularfunctions(basedonGeneOntologyterms).Weidentifiedasetofprocessesorfunctionsthatarecommontoallthesecancers,aswellasthosethatarespecifictoonlyoneorpartialcancertypes.Similarly,proteininteractionnetworksinnucleicacidmetabolismwerecomparedtoidentifythecommon/specificclustersofproteinsacrossdifferentcancertypes.Ourresultsprovideabasisforfurtherexperimentalinvestigationstostudyproteininteractionnetworksassociatedwithcancer.Themethodologydevelopedinthisworkcanalsobeappliedtostudysimilardiseasesystems.
简介:Heterogeneousnuclearribonucleoproteins(hnRNPs)arespliceosomalmacromolecularassemblagesandthusactivelyparticipateinpre-mRNAmetabolism.Theyarecomposedofevolutionarilyconservedandtandemlyrepeatedmotifs,wherebothRNA-bindingandprotein-proteinrecognitionoccurtoachievecellularactivities.Byyetunknownmechanisms,theseribonucleoprotein(RNP)particlesaretargetedbyautoantibodiesandhenceplaysignificantroleinavarietyofhumansystemicautoimmunediseases.Thisfeaturemakesthemimportantprognosticmarkersintermsofmolecularepidemiologyandpathogenesisofautoimmunity.SinceRNPdomainisoneofthemostconservedandwidespreadscaffolds,evolutionalysesoftheseRNA-bindingdomainscanprovidefurthercluesondisease-specificepitopeformation.ThestudypresentedhereinrepresentsasequencecomparisonofRNA-recognitionregionsofrecentlyclonedandcharacterizedhumanhnRNPA3withthoseofotherrelevanthnRNPA/B-typeproteins.Theirimplicationsinhumanautoimmunityareparticularlyemphasized.
简介:Accurateidentificationofprotein-codingregions(exons)inDNAsequenceshasbeenachallengingtaskinbioinformatics.Particularlythecodingregionshavea3-baseperiodicity,whichformsthebasisofallexonidentificationmethods.Manysignalprocessingtoolsandtechniqueshavebeenappliedsuccessfullyfortheidentificationtaskbutstillimprovementinthisdirectionisneeded.Inthispaper,wehaveintroducedanewpromisingmodel-independenttime-frequencyfilteringtechniquebasedonS-transformforaccurateidentificationofthecodingregions.TheS-transformisapowerfullineartime-frequencyrepresentationusefulforfilteringintime-frequencydomain.Thepotentialoftheproposedtechniquehasbeenassessedthroughsimulationstudyandtheresultsobtainedhavebeencomparedwiththeexistingmethodsusingstandarddatasets.Thecomparativestudydemonstratesthattheproposedmethodoutperformsitscounterpartsinidentifyingthecodingregions.
简介:Animprovedmethod,calledAlternativeSpectralRotation(ASR)measure,forpredictingproteincodingregionsinriceDNAhasbeendeveloped.ThemethodisbasedontheSpectralRotation(SR)measureproposedbyKotlarandLavner,anditsaccuracyishigherthanthatoftheSRmeasureandtheSpectralContent(SC)measureproposedbyTiwarietal.Inordertoincreasetheidentifyingaccuracy,wechosethreedifferentcodingcharacters,namelytheasymmetric,purine,andstop-codonvariablesasparameters,andanapprovingresultwaspresentedbythemethodofLinearDiscriminantAnalysis(LDA).
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.
简介:植物非特定的类脂化合物转移蛋白质(nsLtps)被报导了对细菌、真菌的病原体涉及植物防卫活动。在这研究,我们识别了135(122通常认为并且13以前识别了)SolanaceaensLtps,它被聚类进8个不同的组。由与Boutrot的nsLtp分类作比较,我们分类这八个组进五种类型(我,II,IV,IX和X)。我们把SolanaceaensLtps与Arabi-dopsis和GramineaensLtps作比较并且发现(1)那打字我,II和IV被Solanaceae,Gramineae和Arabidopsis分享;(2)类型III,V,VI和VIII被Gramineae和Arabidopsis分享然而并非到目前为止在Solanaceae检测了;(3)而类型IX在Arabidopsis和Solanaceae仅仅是在场的,类型VII仅仅在Gramineae被发现;(4)类型X是在我们的数据说明52.59%SolanaceaensLtps的一种新类型,并且到目前为止没在任何另外的植物被报导。我们进一步造了并且比较了八个组的三维的结构,并且发现在nsLtp家庭以内的主要功能的多样化能被早于到monocot/dicot分叉,并且许多基因复制和顺序变化在monocot/dicot分叉以后发生在nsLtp家庭,特别在Solanaceae。
简介:小RNA(sRNAs)是直接在房间施加他们的功能的非编码的抄本。sRNAs的鉴定由于清楚的顺序和结构的偏爱的缺乏是一项困难的任务。大多数sRNAs在类以内被识别在相关染色体的特定的intergenic区域。然而,几个这些区域仍然保持由于顺序相同或有势力的缺乏未注解统计鉴定工具。一台计算引擎被造了在intergenic区域以内寻找在Enterobacteriaceae染色体识别并且粗略地注解新通常认为的sRNA区域。在相关询问染色体识别类似的sRNA区域作为模板利用试验性地已知的sRNA数据和他们的flankinggenes/KEGGOrthology(击倒)数字。搜索引擎不仅有能力为特定的sRNAs定位通常认为的intergenic区域,而且有力量定位保存,洗牌或删除了在询问染色体的基因簇。因为它使用KO术语定位象sRNAs那样的机能上地重要的区域,更进一步,到另外的基因的击倒数字赋值将增加敏感。PsRNA服务者通过从兴趣的sRNA检索的信息被用于通常认为的sRNA区域的鉴定。计算引擎在http://bioserver1.physics.iisc.ernet.in/psrna/和http://bicmku.in:8081/psrna/在网上是可得到的。
简介:蛋白质领域被保存,在相互作用起一个重要作用在之中的机能上地独立的结构联系了蛋白质。域域相互作用最近被用来预言蛋白质蛋白质相互作用(PPI)。一般来说,一双领域的相互作用概率用训练得分功能被获得。令人满意阀值,当“交往”,带那些领域的蛋白质对被考虑。在这研究,蛋白质的签名内容被利用在Saccharomycescerevisiae,Caenorhabditiselegin,和人预言PPI对现代人。蛋白质签名模式的类似被获得,PPI预言基于二进制类似得分函数被拉。结果证明由建议途径的预言的真积极的率用最大的可能性评价方法比那高是约32%,导致在与一个测试集合相比操作的接收装置下面的区域的22%增加什么时候特征(巨鸟)曲线。当包含一个或二签名的蛋白质被移开时,预言的PPI对的敏感显著地增加了。预言的PPI对是平均,11更多半预定在0.95的信心水平比随机的选择交往,并且平均,4比那些由也预言更好预定种系发生的介绍或基因表达介绍。
简介:流行性感冒A病毒(H1N1),人的地方性的紧张的一个基因分类,鸟并且猪流感,穿过种类障碍到人并且显然获得了人的能力到人的传播。因为NS1蛋白质禁止抗病毒的干扰素/生产,H5N1子类型的一些紧张是高度剧毒的。另一蛋白质NS2调停到通过出口的细胞质的从原子核的病毒的ribonucleoprotein的出口信号。在这份报纸,我们学习了H1N1子类型的这些蛋白质的结构功能关系并且决定了他们的致病力的原因。我们的结果证明非保守的变化稍微稳定了或使动摇NS1或NS1-dsRNA建筑群的结构的域,稍微因此增加了或减少NS1蛋白质并且因而的函数提高了或减少H1N1病毒的致病力。不同紧张的NS2蛋白质在不同领域带了非保守的变化,导致功能的细微损失。这些变化稍微减少了病毒的致病力。因此,结果证实这些病毒的蛋白质的结构功能关系。
简介:TheE(envelope)proteinisthesmalleststructuralproteininallcoronavirusesandistheonlyviralstructuralproteininwhichnovariationhasbeendetected.WeconductedgenomesequencingandphylogeneticanalysesofSARS-CoV.Basedongenomesequencing,wepredictedtheEproteinisatransmembrane(TM)pro-teincharacterizedbyaTMregionwithstronghydrophobicityandα-helixcon-formation.Weidentifiedasegment(NH2-_L-Cys-A-Y-Cys-Cys-N_-COOH)inthecarboxyl-terminalregionoftheEproteinthatappearstoformthreedisulfidebondswithanothersegmentofcorrespondingcysteinesinthecarboxyl-terminusoftheS(spike)protein.ThesebondspointtoapossiblestructuralassociationbetweentheEandSproteins.OurphylogeneticanalysesoftheEproteinsequencesinallpub-lishedcoronavirusesplaceSARS-CoVinanindependentgroupinCoronaviridaeandsuggestanon-humananimalorigin.
简介:管理生命的自然现象的内在的原则是在最近的年里收到到期的重要性的关键问题之一。没有规模的建筑学的特色是大多数连接节点(中心)的活力。这篇文章的主要目的是由在二个相互作用系统的拓扑的参数上考虑建筑上的模式和中心的移动的后果分析蛋白质蛋白质和果蝇melanogaster的新陈代谢的相互作用网络。分析证明两个相互作用网络跟随一个没有规模的模型,建立从改变的状况,很真实的世界网络遵循小世界模式的事实。平均路径长度出现了一双重并且三方面的增加(从9.42~20.93并且从5.29~17.75变化,分别地)分别地,由于中心的删除为蛋白质蛋白质和新陈代谢的相互作用联网。相反,节点的任意的消除没在蛋白质蛋白质和新陈代谢的相互作用网络的拓扑的参数显示出任何显著不同(平均路径长度:9.42+/-0.02和5.27+/-0.01,分别地)。为二个盒子的这越轨行为强调大多数连接节点的意义到网络的自然拓扑学。
简介:植物蛋白质蛋白质相互作用网络没被大规模实验识别了。以便更好在米饭理解蛋白质相互作用,预言的米饭Interactome网络(PRIN;http://bis.zju.edu.cn/prin/)介绍76,585个预言的相互作用包含5,049米饭蛋白质。在印射米饭的genomic特征以后(去注解,subcellular本地化预言,和基因表示),我们发现一个注解得好、生物学上重要的网络是足够富有的在高顺序的生物系统以内捕获许多重要功能的连接,例如小径和生物进程。而且,我们作为例子拿了疯盒子的包含域的蛋白质和生理节奏的节奏发信号小径证明功能的蛋白质建筑群和生物小径能有效地在我们的预言的网络被扩展。在PRIN的扩展分子的网络更加改进了这些分析的能力集成存在知识并且提供新奇卓见进基因和基因网络的功能和协作。
简介:ThenameofSRproteinsisderivedfromtheirtypicalRSdomainthatisrichinserine(Ser,S)andarginine(Arg,R).Theyareconservedinevolution.Uptonow,10membersoftheSRproteinfamilyhavebeenidentifiedinhumans.SRproteinscontainoneortwoRNAbindingmotifsasidefromtheRSdomain,andalsopossessspecialbiochemicalandimmunologicalfeatures.AstothefunctionsofSRproteins,theyfacilitatetherecruitmentofthecomponentsofsplicesomeviaprotein-proteininteractiontoprompttheassemblyofearlysplicesome;whileinalternativesplicing,tissue-specificallyexpressedSRproteinalongwiththerelativeratioofSRproteinandheterogeneousnuclearribonucleoprotein(hnRNP)iscomposedoftwomainregulativemechanismsforalternativesplicing.Almostallofthebiochemicalfunctionsareregulatedbyreversiblephosphorylation.
简介:WedescribetheGALT-Protdatabaseanditsrelatedweb-basedapplicationthathavebeendevelopedtocollectinformationaboutthestructuralandfunctionaleffectsofmutationsonthehumanenzymegalactose-1-phosphateuridyltransferase(GALT)involvedinthegeneticdiseasenamedgalactosemiatypeI.Besidesalistofmissensemutationsatgeneandproteinsequencelevels,GALT-ProtreportstheanalysisresultsofmutantGALTstructures.Inadditiontothestructuralinformationaboutthewild-typeenzyme,thedatabasealsoincludesstructuresofover100singlepointmutantssimulatedbymeansofacomputationalprocedure,andtheanalysistoeachmutantwasmadewithseveralbioinformaticsprogramsinordertoinvestigatetheeffectofthemutations.Theweb-basedinterfaceallowsqueryingofthedatabase,andseverallinksarealsoprovidedinordertoguaranteeahighintegrationwithotherresourcesalreadypresentontheweb.Moreover,thearchitectureofthedatabaseandthewebapplicationisflexibleandcanbeeasilyadaptedtostoredatarelatedtootherproteinswithpointmutations.GALT-Protisfreelyavailableathttp://bioinformatica.isa.cnr.it/GALT/.
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.
简介:Microsatellitesorsimplesequencerepeats(SSRs)havebeenfoundinmostorganismsduringthelastdecade.Sincelarge-scalesequencesarebeinggenerated,especiallythosethatcanbeusedtosearchformicrosatellites,thedevelopmentofthesemarkersisgettingmoreconvenient.KeepingSSRsinviewingtheimportanceoftheapplication,availableCDS(codingsequences)orESTs(expressedsequencetags)ofsomeeukaryoticspecieswereusedtostudythefrequencyanddensityofvarioustypesofmicrosatellites.OnthebasisofsurveyingCDSorESTsequencesamountingto66.6Mbinsilkworm,37.2Mbinfly,20.8Mbinmosquito,60.0Mbinmouse,34.9Mbinzebrafishand33.5MbinCaenorhabditiselegans,thefrequencyofSSRswas1/1.00Kbinsilkworm,1/0.77Kbinfly,1/1.03Kbinmosquito,1/1.21Kbinmousey1/1.25Kbinzebrafishand1/1.38KbinC.Elegans.TheoverallaverageSSRfrequencyofthesespeciesis1/1.07Kb.Hexanucleotiderepeats(64.5%-76.6%)arethemostabundantclassofSSRintheinvestigatedspecies,followedbytrimeric,dimeric,tetrameric,monomericandpentamericrepeats.Furthermore,theA-richrepeatsarepredominantineachtypeofSSRs,whereasG-richrepeatsarerareinthecodingregions.
简介:Proteinphosphorylationplaysanimportantroleinvariouscellularprocesses.Duetoitshighcomplexity,themechanismneedstobefurtherstudied.Inthelastfewyears,manymethodshavebeencontributedtothisfield,butalmostalloftheminvestigatedthemechanismbasedonproteinsequencesaroundproteinsites.Inthisstudy,weimplementanexplorationbycharacterizingthemicroenvironmentsurroundingphosphorylatedproteinsiteswithamodifiedshellmodel,andobtainsomesignificantpropertiesbytherank-sumtest,suchasthelackofsomeclassesofresidues,atoms,andsecondarystructures.Furthermore,wefindthatthedepletionofsomepropertiesaffectsproteinphosphorylationremarkably.Ourresultssuggestthatitisameaningfuldirectiontoexplorethemechanismofproteinphosphorylationfrommicroenvironmentandweexpectfurtherfindingsalongwiththeincreasingsizeofphosphorylationandproteinstructuredata.
简介:Thenucleocapsidprotein(Nprotein)hasbeenfoundtobeanantigenicproteininanumberofcoronaviruses.WhethertheNproteininsevereacuterespiratorysyndrome-associatedcoronavirus(SARS-CoV)isantigenicremainstobeelucidated.UsingWesternblotandEnzyme-linkedImmunosorbentAssay(ELISA),therecombinantNproteinsandthesynthesizedpeptidesderivedfromtheNproteinwerescreenedinserafromSARSpatients.AllpatientserainthisstudydisplayedstrongpositiveimmunoreactivitiesagainsttherecombinantNproteins,whereasnormalseragavenegativeimmunoresponsestotheseproteins,indicatingthattheNproteinofSARS-CoVisanantigenicprotein.Furthermore,theepitopesitesintheNproteinweredeterminedbycompetitionexperiments,inwhichtherecombinantproteinsorthesynthesizedpeptidescompetedagainsttheSARS-CoVproteinstobindtotheantibodiesraisedinSARSsera.OneepitopesitelocatedattheC-terminuswasconfirmedasthemostantigenicregioninthisprotein.AdetailedscreeningofpeptidewithELISAdemonstratedthattheaminosequencefromCodons371to407wastheepitopesiteattheC-terminusoftheNprotein.UnderstandingoftheepitopesitescouldbeverysignificantfordevelopinganeffectivediagnosticapproachtoSARS.
简介:Functionalcharacterizationofeverysingleproteinisamajorchallengeofthepostgenomicera.Thelarge-scaleanalysisofacell'sproteins,proteomics,seekstoprovidetheseproteinswithreliableannotationsregardingtheirinteractionpartnersandfunctionsinthecellularmachinery.Animportantsteponthiswayistodeterminethesubcellularlocalizationofeachprotein.Eukaryoticcellsaredividedintosubcellularcompartments,ororganelles.Transportacrossthemembraneintotheorganellesisahighlyregulatedandcomplexcellularprocess.Predictingthesubcellularlocalizationbycomputationalmeanshasbeenanareaofvividactivityduringrecentyears.Thepubliclyavailablepredictionmethodsdiffermainlyinfouraspects:theunderlyingbiologicalmotivation,thecomputationalmethodused,localizationcoverage,andreliability,whichareofimportancetotheuser.Thisreviewprovidesashortdescriptionofthemaineventsintheproteinsortingprocessandanoverviewofthemostcommonlyusedmethodsinthisfield.