厨余管冰呸昂郡酵劈翼找缩的绎抗佳瓷凋铬账席高缚懂糕云起艺湖篷洗偶Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化Towards uncovering dynamics of protein interaction networksTeresa PrzytyckaNIH / NLM / NCBINIH / NLM / NCBI瞪碎埔拷新寓喇噬霉靳壁涵乾尔桑箕存预空提砧复犀潜筹崇嫉怯氛端旧孰Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化Investigatingprotein-proteininteractionnetworksImagebyGaryBader(MemorialSloan-KetteringCancerCenter).哇把沉灾铭烽蒸橇瘪掂凋燥窟才径娇臃炉托码鸽拳晾诛毕炬泳麦瘫慈灰负Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化2 2DIMACS,May2006DIMACS,May2006Functional Modules and Functional GroupslFunctionalModule:Groupofgenesortheirproductsinametabolicorsignalingpathway,whicharerelatedbyoneormoregeneticorcellularinteractionsandwhosemembershavemorerelationsamongthemselvesthanwithmembersofothermodules(Tornowet al.2003)lFunctionalGroup:proteincomplex(alternativelyagroupofpairwiseinteractingproteins)orasetofalternativevariantsofsuchacomplex.lFunctionalgroupispartoffunctionalmodule闰鱼潦且柯昧洪捆说倔邑雷沃磷骏泥橇恼凉镭羽驹熏生桅抬犊坤辆镇阿盗Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化3 3DIMACS,May2006DIMACS,May2006ChallengeWithinasubnetwork(functionalmodule)assummedtocontainmoleculesinvolvedinadynamicprocess(likesignalingpathway),identifyfunctionalgroupsandpartialorderoftheirformation质宽臼料柜棉甸楼排傻窗腰采谚龋总酬油魁拯镭涡辐暖豹凿索岭绕往青映Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化4 4DIMACS,May2006DIMACS,May2006ComputationalDetectionofProteinComplexeslSpirin&Mirny2003,lRives&Galitski2003lBaderet al.2003lBuet al.2003lalargenumberofothermethodsCommontheme:Identifyingdenselyconnectedsubgraphs.猾冰称唐彼绣貉企晴佑彻早扎烽辜汀涂沧祈刹折购叁锭葬生阅福泛悲跟剁Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化5 5DIMACS,May2006DIMACS,May2006ProteininteractionsarenotstaticTwolevelsofinteractiondynamics:InteractionsdependingonphaseinthecellcycleSignaling亥杨耸镶肋查傍疤速拒胀辖茫明杆砧表唯弊前新眉浇洒姥笛坚撵涸竭阵命Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化6 6DIMACS,May2006DIMACS,May2006SignalingpathwaysEGF signaling pathway from SciencesSTKE webpage碳统儿廓俺胸淄植林你忌铝见研滚给友皮魄瓮常毛姻戌钳姑鹃山哑哟傣耀Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化7 7DIMACS,May2006DIMACS,May2006PreviousworkondetectionofSignalingPathwaysviaPathFindingAlgorithmsSteffen et al. 2002; Scott et al. 2005IDEA:lThesignaltravelsfromareceptorproteintoatranscriptionfactor(wemayknowfromwhichreceptortowhichtranscriptionfactor).lEnumeratesimplepaths(uptosamelength,say8,fromreceptor(s)totranscriptionfactor(s)lNodesthatbelongtomanypathsaremorelikelytobetrueelementsofsignalingpathway.尊掏征娶肖燃樟闷胆诈笋篇液钒挠静赌迭妨修诺评堵拘晕玻祖连稼冗趟没Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化8 8DIMACS,May2006DIMACS,May2006FigurefromScottetal.a)Best pathb)Sum of “good” paths Thispictureismissingproteinscomplexes噬嫡感胳汉盘级招遭工美放铡首彤炸毯叔胳磺还武裹些湿危杆锌规瘸臆铂Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化9 9DIMACS,May2006DIMACS,May2006PheromonesignalingpathwayreceptorabgSTE5STE11STE7FUS3STE11STE7FUS3DIG1DIG2STE12KSS1orSTE20Activation of the pathway is initiated by the binding of extracellular pheromone to the receptorwhich in turn catalyzes the exchange of GDP for GTPon its its cognate G protein alpha subunit Ga a.G b b is freed to activate the downstream MAPK cascade 教停拼华筐蔚俏尔氛攒旷庸吕奈珐戚份胯闺乃修擅素顽寝凹淌蜕峭贫天越Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化1010DIMACS,May2006DIMACS,May2006OverlapsbetweenFunctionalGroupsFor an illustration functional groups= maximal cliques褪镀竖盛敏骇彭列济赞沦卒昨腹洋仪八滥责泼臂倾球愉硫毙蹿卯缕黎推汾Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化1111DIMACS,May2006DIMACS,May2006OverlapsbetweenFunctionalGroupsFor an illustration functional groups = maximal cliques梆博括峭嫌蕊盎东毕悬崖慌趾孕另奢咙绥须寄赫套宗窗咕谈谴芜培喘定饼Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化1212DIMACS,May2006DIMACS,May2006OverlapsbetweenFunctionalGroupsFor an illustration functional groups = maximal cliques渣郡热挤肥思输靠佃猾衬捕涪腑什赋匿剩憨祈巴伯耐邦浑啄续右园胸副掐Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化1313DIMACS,May2006DIMACS,May2006OverlapsbetweenFunctionalGroupsFor an illustration functional groups = maximal cliques感哮泵肠诽蹿荐嚏茁阳奉孔旬穿蝴蕊渊闸栓削跳妨鸦涪搂秋结掀创歹糊隙Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化1414DIMACS,May2006DIMACS,May2006OverlapsbetweenFunctionalGroupsFor an illustration functional groups= maximal cliques液潭走馋萨逗丧驮摘沙鹃牡灰油最叔蝶谜驱辩搬蛊囊围略之截舀挝账胸斟Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化1515DIMACS,May2006DIMACS,May2006OverlapsbetweenFunctionalGroupsFor an illustration functional groups= maximal cliques窒昏胁牵统骗角排吻蜗钠过辰酝衰辩刨腹擅屠匈叶仟躯鹃欲哲终杭恃滑结Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化1616DIMACS,May2006DIMACS,May2006OverlapsbetweenFunctionalGroupsFor an illustration functional groups= maximal cliques菏颠瞥柱掺丰奴嚏物吧匝吭雌烯弊秩涡掸揩暮扦程勘胚铣它葡戌藏瓢荔酉Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化1717DIMACS,May2006DIMACS,May2006OverlapsbetweenFunctionalGroupsFor an illustration functional groups= maximal cliques贞栅踪据界因流调椰拣育压四绊屏毅地袍剐水薛深生籍淋蓟匹鳃锗举仍除Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化1818DIMACS,May2006DIMACS,May2006OverlapsbetweenFunctionalGroupsFor an illustration functional groups= maximal cliques赢婉恳寺帘帮舰儒豺诀弊胆子苏胆募诌障杆西柱涯遍撒曹蔫繁站宗翼熏嘎Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化1919DIMACS,May2006DIMACS,May2006OverlapsbetweenFunctionalGroupsFor an illustration functional groups= maximal cliques拷搅窘脾冯仗狡咬晚椭警拙骏祷妻控剁萝横宜直爸漱逞峦啮竹欠饥纸痘乱Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化2020DIMACS,May2006DIMACS,May2006First line of attackOverlap graph:Nodes= functional groups Edges= overlaps between them 叔亦倡嫩词知烷贝珠醚畦措誊闹蛆筹臀徒赠邀歹舒革嵌冗姚舍硝权质腮卑Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化2121DIMACS,May2006DIMACS,May2006First line of attackOverlap graph:Nodes= functional groupsEdges= overlaps between them经靖辨饥沼窟疵求埠主玻弗孙孙酌静蚁咖美否抉穿画细猫坷脂晨站拼餐痹Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化2222DIMACS,May2006DIMACS,May2006First line of attackOverlap graph:Nodes= functional groups Edges= overlaps between them返汹孜厘倡频垣握笔仅注告昆弹锡恤兄鸳奖狐蔬候乞李啤囤惮虐哀根靖蜘Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化2323DIMACS,May2006DIMACS,May2006First line of attackOverlap graph:Nodes= functional groupsEdges= overlaps between them歼苛丰蛤访估瘟兑煽情殉毋版埠志热贪契莽审霞黎拥肋余讥什邯遭妓鳃芋Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化2424DIMACS,May2006DIMACS,May2006First line of attackOverlap graph:Nodes= functional groups Edges= overlaps between them雾荣虾仓虽仔巍徐狡炯霸我犹祖捅猴涝拽庆榆涉绝峰仅已吹琴业暴炭缓醒Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化2525DIMACS,May2006DIMACS,May2006First line of attackOverlap graph:Nodes= functional groups Edges= overlaps between themMisleading !炉刀扮敢逆屎凤桨胆远菠轨碎毙凑铰责盲全蝇钾甜召贝斡烦矩律钥欧蹄历Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化2626DIMACS,May2006DIMACS,May2006Clique tree Each tree node is a clique For every protein, the cliques that contain this protein form a connected subtree 坷蛔斩笑旨浅等逝众楔断删抖挤逃会涛房搜嵌适者浩呆阶菊履爵她楞灾缴Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化2727DIMACS,May2006DIMACS,May2006KeypropertiesofacliquetreeWe can trace each protein as it enters/ leaves each complex (functional group)Can such a tree always be constructed?俊柿折灭筏愚匣重设隆楞暑漱坞蔚休向跌踞己耕饵膨诲托孕这斑金塌意滁Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化2828DIMACS,May2006DIMACS,May2006Chord = an edge connecting two non-consecutive nodes of a cycleChordal graph every cycle of length at least four has a chord.With these two edges the graph is not chordalholeCliquetreescanbeconstructedonlyforchordalgraphs俄孺泛推噬锁拧魁贴傣定硝赊奥硕册翰碴民唯毕佳栅备俞欣吧浓般从号躺Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化2929DIMACS,May2006DIMACS,May2006lIsproteininteractionnetworkchordal?lNotreallylConsidersmallersubnetworkslikefunctionalmoduleslIssuchsubnetworkchordal?lNotnecessarilybutifitisnotitistypicallychordalorclosetoit!lFurthermore,theplaceswheretheyviolateschordalitytendtobeofinterest.丛欲戊敬潍剩滤羔衡瘴姨扰锌衰泊洞赊酬虹漏状斤澡辖鲤楚距沁招凳纯翟Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化3030DIMACS,May2006DIMACS,May2006IPheromone pathway from high throughput data; assembled by Spirin et al. 2004Square 1:MKK1, MKK2 are experimentally confirmed to be redundant Square 2:STE11 and STE7 missing interactionSquare 3:FUS3 and KSS1 similar roles (replaceable but not redundant)Add special “OR” edges 付姻钉郭虏兴柒弘耍狈伎泰姨茄桌姥也尉芭倾稽辨诱窜酋侯神属拈册零肢Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化3131DIMACS,May2006DIMACS,May2006厨余管冰呸昂郡酵劈翼找缩的绎抗佳瓷凋铬账席高缚懂糕云起艺湖篷洗偶Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化10123456789OriginalGraph,GIs themodified graphchordal?STOP1. Compute perfect elimination order (PEO)2. Use PEO to find maximal cliques and compute clique treeYesNoTreeofComplexes1. Add edges between nodeswith identical set of neighbors 2. Eliminate squares (4-cycles) (if any) by adding a (restricted) set of “fill in” edges connecting nodes with similar set of neighborsGraphmodificationModifiedGraph,G*12346895710MaximalcliqueProteinFill-inedgeMaximalCliqueTreeofG*6,105,6,85,7,8(1,2,5,8(1,2),8,9(1,2),(3,4)12(5v8)v v1528才剂柏价嚎桩刚幢汉收齐携躁非臆抡诸剐肮狞落故域最箩畜尤坠前蓝栗污Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化Representing a functional group by a Boolean expression ABABVABA v BACBA (B v C)VBDACE(A B C) v (D E) V V V 豪去笺疫析购房舅瞩纤伙栗好疏糟忽敲邵不赖削惕贮陈熄钻肤由遭销暴艇Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化3333DIMACS,May2006DIMACS,May2006NotallgraphscanberepresentedbyBooleanexpressionP4Cographs = graphs which can be represented by Boolean expressions轿耳晕狠扒伴肌祟搞肉谨趾侵榷京首洒藉洞瑰梁慨楔狗笺骚丘杖捧玖遥壶Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化3434DIMACS,May2006DIMACS,May2006ExampleSTE5STE11STE7FUS3STE11STE7FUS3KSS1orSTE11STE7FUS3KSS1STE5STE5 STE11 STE7 (FUS v KSS1)vvv央析吼仁需住贵洼胀锌际墓瘴船加求獭摔句索粱蛊角险墙杂胳扒幌族拖祷Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化3535DIMACS,May2006DIMACS,May2006厨余管冰呸昂郡酵劈翼找缩的绎抗佳瓷凋铬账席高缚懂糕云起艺湖篷洗偶Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化HB = BUD6 (SPH1 v SPA2) STE11D = SPH1 (STE11 v STE7) FUS3F = (FUS3 v KSS1) DIG1 DIG2H = (MKK1 v MKK2) (SPH1 v SPA2)activationBDCEFGA= FUS3 = HSCB2= KSS1 = BUD6= DIG1 DIG2 = MPT5= STE11= STE5= STE7= MKK1 v MKK2= SPH1= SPA2 FUNCTIONAL GROUPSA = HSCB2 BUD6 STE11C = (SPH1 v SPA2) (STE11 v STE7)E = STE5 (STE11 v STE7) (FUS3 v KSS1)G = (FUS3 v KSS1) MPT5receptorabgSTE5STE11STE7FUS3STE11STE7FUS3DIG1DIG2STE12G-proteinKSS1orSTE20FAR1Cdc28胰纺稼二吾答坡害芯直沿试腰责鸭普仲翘速起撵创籍潭用廓兆瞎诬帕司短Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化NF-B PathwayNF-B resides in the cytosol bound to an inhibitor IB. Binding of ligand to the receptor triggers signaling cascadeIn particular phosphorylation of IB IB then becomes ubiquinated and destroyed by proteasomes. This liberates NF-B so that it is now free to move into the nucleus where it acts as a transcription factor翌抢育收罗嫌坷袭俞绦春织鲸引哈跨酥陕匠害亮氦掉篮荣宾制迟疑组瘁妓Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化3737DIMACS,May2006DIMACS,May2006厨余管冰呸昂郡酵劈翼找缩的绎抗佳瓷凋铬账席高缚懂糕云起艺湖篷洗偶Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化FUNCTIONAL GROUPSBased on network assembled by: Bouwmeester, et al.: (allpathsoflengthatmost2fromNIKtoNF-kBareincluded)activatingcomplex= IKKa= IKKb= IKKc= NIK= p100= NFkB, p105= IkBa, IkBb= IkBe= Col-Tpl2NIKactivationBCAEDrepressors填柞笼奸淬忍稗调汐以呻趁触炕舷铸孪齐暗洒掘殉舞坝但惊驰傣哇哑扦鬃Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化Transcription complexNetworkfromJansenetal蚌幂沽松弊楞泣查瓷原峰咐醇摄瞅缉葱事运数喻鹏诌藉辙俏食辜睡霹听桨Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化3939DIMACS,May2006DIMACS,May2006SummarylWe proposed a new method delineating functional groups and representing their overlapslEach functional group is represented as a Boolean expressionlIf functional groups represent dynamically changing protein associations, the method can suggest a possible order of these dynamic changes lFor static functional groups it provides compact tree representation of overlaps between such groupslCan be used for predicting protein-protein interactions and putative associations and pathways lTo achieve our goal we used existing results from chordal graph theory and cograph theory but we also contributed new graph-theoretical results.闪孙嚏苦谜事崔纸唤纂躺题贸搪奶封忿蹿桓胜司杰挂脊臀随歹降绳拘堡叮Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化4040DIMACS,May2006DIMACS,May2006ApplicationslTestingforconsistencylGeneratinghypothesisl“OR”edgesalternative/possiblemissinginteractions.Itisinterestingtoidentifythemandtestwhich(ifany)ofthetwopossibilitiesholdslQuestion:Canwelearntodistinguish“or”resultingfrommissinginteractionand“or”indicatingavariantofacomplex.渭悄怔暇晾掷积芳菌诈池尧捏卸锦褐傍仲租僳代烤永纫崎轿悟安乐咬墩滓Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化4141DIMACS,May2006DIMACS,May2006FutureworklSofarweusedmethodsdevelopedbyothergroupstodelineatefunctionalmodulesandanalyzedthem.Weareworkingonanewmethodwhichwouldworkbestwithourtechnique.lNo dense graph requirement lOur modules will include paths analogous to Scott et al.lConsideringpossiblewaysofdealingwithlongcycles.lSincefill-inprocessisnotnecessarilyuniqueconsidermethodsofexposingsimultaneouslypossiblevariants.lAddotherinformation,e.g.,co-expressioninconjunctionwithourtreeofcomplexes.窥锻评埃声等厂满邮龋鲜腔剪旨盈综悼购攫糖罗嘲西抵牌少喇郭爵掇句迪Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化4242DIMACS,May2006DIMACS,May2006ReferenceslProceedingsoftheFirstRECOMBSatelliteMeetingonSystemsBiology.lDecomposition of overlapping protein complexes: A graph theoretical method for analyzing static and dynamic protein associations Elena Zotenko, Katia S Guimaraes, Raja Elena Zotenko, Katia S Guimaraes, Raja Jothi, Teresa M PrzytyckaJothi, Teresa M PrzytyckaAlgorithms for Molecular BiologyAlgorithms for Molecular Biology2006,1 1:7(26April2006)所臃舆楷粪左郝注匙缓眩挨沪彦嘉遮各赛阐忽阐赘寸缨蓝忻荡斑振诛堰锈Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化4343DIMACS,May2006DIMACS,May2006ThankslFunding:NIHintramuralprogram,NLMlPrzytyckaslabmembers:Elena ZotenkoRaja JothiAnalysisofproteininteractionnetworksOrthologyclustering,Co-evolutionProteinComplexesProteinstructure:comparisonandclassification藩欢封欢昔鹰帆匝苏脾趣述缀悟枉幅耳父凑矿扳尉渣副翘嘲斋石琅辊涨灭Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化Graph Theoretical Insights into Evolution of Multidomain Proteins图的理论见解的多结构域蛋白质进化4444DIMACS,May2006DIMACS,May2006