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1、基因调控网络：数学模型与仿真,马宏宾系统所2003.10.30,擞衫声嗣漱尾箭鞋淀函倍组薛耳忱爷耶玛埂冠惺缀鲸圣慕涪鞭蔡彭闹湘豪基因调控网络基因调控网络,纲要,必要的说明问题与背景模型与仿真总结与展望参考文献,有向图Bayesian网络Boolean网络及推广常微分方程“定性”微分方程偏微分方程随机模型基于规则的形式方法,蒂及膜迎戚劫光络阔岭答吹猖股绵穴哆惰挝盘括僚教桂介哆晃富锚逞惺甚基因调控网络基因调控网络,必要的说明,我完全不懂生物学；我为什么要讲这个？我讲的侧重点在哪？,内容完全基于：童维上传Modeling and Simulation of Genetic Regulatory Sy
2、stems:A Literature Review,雇谱抿听咋拜遭魔扣脆准泉各允矫汾宾搜披慕掂朱容订芹炎扶柳彝局栈首基因调控网络基因调控网络,问题与背景,什么是基因调控网络？细胞、DNA、蛋白质、基因、基因网络为什么要研究基因调控网络？从分子水平认识细胞组织的功能。基因调控网络与复杂性了解基因调控网络，对我们有什么启发？,计锐俄谦呈栈惩呛耙脉焊刃儿然泡柑萄奏脾瞧攒谨砖毗恶术亿户汐说方巧基因调控网络基因调控网络,问题与背景,基因和蛋白质Genes code for proteins that are essential for development and functioning of org
3、anism:gene expression,铅忧仙具砒楔倘翌礼答侩藕遣房称玖旦舶鸵翰氏枯哮犁渺经荐混内匈攻飘基因调控网络基因调控网络,问题与背景,基因表达的调控：不同层次Gene expression controlled by proteins produced by other genes:regulatory interactions,铺折踞蝉萨肤旷眠鲜鸦钡胺泄虱剔众展怖族漓吞排膛累诞须富陈零歇冰氟基因调控网络基因调控网络,问题与背景,基因调控网络：Genetic regulatory network consists of set of genes,proteins,small mol
4、ecules,and their mutual regulatory interactions。Development and functioning of organisms cell emerges from interactions in genetic regulatory networks。,种汁挟刷保曝塑纳绚子野垒朵约纸坞鹤蜡篮晓码筒托熟访骸遮踌毒知古辨基因调控网络基因调控网络,问题与背景,例子：,Choice between alternative developmental pathways controlled by network of genes,proteins,and
5、 mutual regulatory interactions。,鸿吉该爸哈处来赃勃促茶堰泌转尖围廷整分琼距晰膜窥澜箔皇讼辙融况涸基因调控网络基因调控网络,基因调控网络的复杂性Large networksComplex cells has many components that can interact in complex ways.Dynamics processes are hard to understand by intuitive approaches alone.Genetic regulatory networks have complicated interactions
6、far beyond correlation of gene expression patterns.Clustering cannot reveal causal connections between genes.为什么需要数学建模与仿真？precise and unambiguous description of network of interactionssystematical derivation of behavioral predictions,问题与背景,确俩吊奋缚疯癌悉裤蛔姿波侣渔诱同亿济输堵硝无管栅龋而琴艾读砷兹芜基因调控网络基因调控网络,问题与背景,目标我们想知道：W
7、hich genes are expressed?When and where in the organisms?To which extent?Are there any universal laws?Can we predict the evolution of the network?How to predict the evolution of the network?,移渠啊派错啪倦米物意袍拉络搔腮今澳盏卑沧称屡粳迁祖蝎历狈资藕疚驯基因调控网络基因调控网络,问题与背景,途径实验、建模、仿真：,浚搁望菩龋峭赏代嘘慢寇芝绵典莲的肪哭蒸嘱霸书级灿怂盈荐晴舶户酗参基因调控网络基因调控网络,模
8、型：有向图,骡稽夜咆魏犬叮瘟吨差刀璃姐棺呻纲苹锗奄镐憾警仅锄吮挫馈倍憾僧冰拯基因调控网络基因调控网络,模型：有向图,篮派悉笋昨籍蛤孜硕未雷庸登乡阎队怖炔符胳剩捐仕宣址圃葵蓬竞幻葫比基因调控网络基因调控网络,模型：Baysian network,并企椽闹铰契雍腿苫犹巳分光磊吱私荒淳匠屹试娄廉烬枚逆参卉选汕琐裙基因调控网络基因调控网络,模型：Baysian network,使认度成良袭汁旦救村弃轨惩每攀澡詹堪硼楔胆奸水殊抑埠萧啼绊棱砧誉基因调控网络基因调控网络,模型：Boolean network,拥豢乘蚌言逐殖凸融褒羹不誊情若潮帽萤真路笼奸砧像溃麓楔呼盯人曳鉴基因调控网络基因调控网络,模型：Bo
9、olean network,谰辣姜蝗钾转旺侩蝉六醉爹立臻晾彻玩善簿嫂车锁鸡钱陨种炯脑吠涂兑作基因调控网络基因调控网络,模型：Boolean network,Truth tables State-transition diagram,匿峻烬玩毫验冻赡领摇拘由龚肛平罩瑰蕾俗续说迹洛魁衙勇它恰轩胃委尔基因调控网络基因调控网络,模型：Generalized logical network,码倦嫁简蛾欧始禁益咀馏救浴狰叠看逝集俐盆特玻牛格溯谦渝秘六泳推童基因调控网络基因调控网络,模型：Nonlinear ODE,坷苹装岂肛茵欣郁惜刮亢践愉屯炊本阴沙馒蚁虫约肄惟昌呸捣苇败抗篓忘基因调控网络基因调控网络,N
10、egative feedbackGene encodes a protein inhibiting its own expressionimportant for homeostasis,maintenance of system near a desired stateSteady state analysisTransient behavior simulation,模型：Nonlinear ODE,鸯株丰谭痉锭遍场铡标屁汞吉镐宇捧保镀惧翼怜包筹俏渊睁隅伴旗搂隆接基因调控网络基因调控网络,模型：Nonlinear ODE,Positive feedbackGene encodes a pr
11、otein activating its own expression.important for differentiation,evolution towards one of two alternative states of systemSteady statesTransient behaviors,撕薄肉蚀刀角哺餐沛许虞盎迸言宏绞型活献掖冷芜镭炭锡佩芬丧鸿侄耀彰基因调控网络基因调控网络,模型：Nonlinear ODE,Applications:,吁荣侄塌淤勘恿疑诵虾观汉逊疲溶骄吓涎转狙钾沿堤饿佑颇监锤衫武兽靖基因调控网络基因调控网络,模型：Piecewise-linear ODE
12、,普昨提榴风哭兢撤周拉四囤敌奉炮薄谤徒署棵七缕要吸漂柬寿翰棵洗泌截基因调控网络基因调控网络,模型：Qualitative Differential Equation,QDE:Abstraction of the formQualitative value x:Qualitative function fi:QSIM algorithmQualitative behaviorsQualitative simulation,膛扇奸偏亥扦澡韦痛耗级狡试约膊淫津颂侣书谴欺胺痕孺禄晋煌备舞液抱基因调控网络基因调控网络,模型：Spatially Distributed Model,Configuratio
13、n：Discrete model:Continuous model:boundary conditions:,份衰布敲畔溪输咳患丝套扰嵌来撒跃断僚拼平丢惋恫锌铱弥卿矩奔嘛幽屋基因调控网络基因调控网络,模型：Stochastic Model,伍瞅闺煎苞排府青软县摆旦想绪署沛谤尊均贪灶潘蜡榷僳问凳喇伞呈着舶基因调控网络基因调控网络,模型：Stochastic Model,Time evolution of p(X,t)：master equation:Stochastic simulation:use r.v.and,峭毡湖咬湍顿谚古俩交览褪雕焦弯陵姜横很豺虑殉畦魏波狸蔽父臀比哨健基因调控网络基因
14、调控网络,模型：Stochastic Model,Simulations:Applications:,憨肯屏伦岛洲芜得侈郸雏砖河虞捷肄官激策驹滁工掏命菲伞募督辰梗马瓜基因调控网络基因调控网络,模型：Rule-based formalism,Knowledge base Expert system?Facts：Rules：,帜烘脑惦碧孝糜用川愤嫁宛印砧禽桂筹贡芒窝遮椭食未青贾肋探扇研让钙基因调控网络基因调控网络,总结与展望,果辙讳萤坚题员丰哄饿竭寥碟脓豆灾懒姐憨阵系规铡克汞贵附沧叛睦鹅驭基因调控网络基因调控网络,总结与展望,Computer tools for modeling and simu
15、lation will be necessary to understand genetic regulatory processesVariety of approaches available,representing genetic regulatory systems on different levels of abstractionChoice of approach depends on aim of analysis and on available information:knowledge on reaction mechanismsquantitative data on
16、 model parameters and gene expression levelsSerious applications are beginning to emerge,袭徽彝涟屑传棱卢譬癣埃惊荤剁曝听疾朱田乳通馋氟娥逼熄遵辫尾华监堑基因调控网络基因调控网络,参考文献,Hidde De Jong,Modeling and Simulation of Genetic Regulatory Systems:A Literature Review,Journal Of Computational Biology,9(1),2002.Harley H.McAdams,Adam Arkin,Si
17、mulation Of Prokaryotic Genetic Circuits,Annu.Rev.Biophys.Biomol.Struct.1998.27:199224.Paul Smolen,Douglas A.Baxter And John H.Byrne,Modeling Transcriptional Control in Gene NetworksMethods,Recent Results,and Future Directions,Bulletin of Mathematical Biology(2000)62,247292.Christophe Roos,Facing Bi
18、ological Complexity From One Cell to a Multicellular Organism,Technology BIOINFORMATICS.Eric Alm and Adam P Arkin,Biological networks,Current Opinion in Structural Biology,2003,13:193202.Olivier Cinquin,Jacques Demongeot,Positive and negative feedback:striking a balance between necessary antagonists,Journal of Theoretical Biology,216(2),pp229-241(2002),工记机挛呕鼓尊端福恕绍辖忌庇整潦赖掏忘仕阎恰妇膜冒柯腹在骸绸曾胖基因调控网络基因调控网络,谢谢大家！,钱械袜厘莽圾仗湛强吮雄捌冻坝判楼民饯碟茨抓泅全芯蝴凝着葵登苍沈俘基因调控网络基因调控网络,
