Control of Genetic Regulatory Networks:Opportunities and Challenges
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摘要: 众所周知,基因调控网络(Genetic regulatory networks,GRNs)是一类基本且重要的生物网络.基因调控网络可以通过输入、噪声、参数以及正负反馈等进行功能的鲁棒性调节与控制.本文首先简要回顾了基因调控网络控制方面的若干研究进展,然后提出了一些与控制相关的基因调控网络的基本科学问题.基因调控网络的控制以生命科学为背景,以控制理论为理论基础.过去几十年,控制论的基本思想与方法逐步渗透到基因调控网络的研究中.同时,来源于生命科学的控制问题也为我们提出了新的机遇与挑战.基因调控网络的控制对生命科学中困扰人类的基本问题,如延长寿命、治愈癌症、糖尿病等顽疾有着非常重要的现实意义.此外,基因调控网络控制研究对合成生物学、网络医学、个性化医学等相关学科的发展具有潜在的应用价值.Abstract: It is well known that genetic regulatory networks (GRNs) are fundamental and important biological networks. This paper briefly reviews the main research progresses in the control of GRNs. Moreover, this paper proposes some fundamental scientific problems for the control of GRNs. In fact, life sciences and control theory are the real-world background and theoretical basis for the control of GRNs, respectively. Over the last few decades, the basic idea and methods of control theory have gradually infiltrated into the research of GRNs. At the same time, some control problems from life sciences also provide new opportunities and challenges for control science. The control of GRNs guides some potential routes to resolve the long-time perplexing problems in life sciences, such as the prolonging of lifespan, curing cancer and diabetes. Furthermore, the control of GRNs has potential real-world applications for the rapid developments of synthetic biology, networked medicine and personalized medicine.
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Key words:
- Systems biology /
- genetic regulatory network (GRN) /
- noise /
- positive feedback /
- negative feedback
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[1] Hood L. Systems biology: integrating technology, biology, and computation. Mechanisms of Ageing and Development, 2003, 124(1): 9-16 [2] Hood L, Health J R, Phelps M E, Lin B Y. Systems biology and new technologies enable predictive and preventative medicine. Science, 2004, 306(5696): 640-643 [3] Kitano H. Systems biology: a brief overview. Science, 2002, 295(5560): 1662-1664 [4] Alon U. An Introduction to Systems Biology: Design Principles of Biological Circuits. London: Chapman and Hall, CRC, 2006 [5] Benner S. Biology from the bottom up. Nature, 2008, 452(7188): 692-694 [6] Kirschner M W. The meaning of systems biology. Cell, 2005, 121(4): 503-504 [7] Bruggeman F J, Westerhoff H V. The nature of systems biology. Trends in Microbiology, 2007, 15(1): 45-50 [8] Mendoza E R. Systems biology: its past, present and potential. Philippine Science Letter, 2009, 2(1): 16-34 [9] Sontag E D. Some new directions in control theory inspired by systems biology. Systems Biology, 2004, 1(1): 9-18 [10] McAdams H, Shapiro L. Circuit simulation of genetic networks. Science, 1995, 269(5224): 650-656 [11] Mandal S, Sarpeshkar R. Circuit models of stochastic genetic networks. In: Proceedings of the 2009 IEEE Biomedical Circuits and Systems Conference. Beijing, China: IEEE, 2009. 109-112 [12] Chen L N, Wang R S, Zhang X S. Biomolecular Networks: Methods and Applications in Systems Biology. Hoboken, New Jersey: Wiley, 2009 [13] Lei Jin-Zhi. Systems Biology-Modelling, Analysis, Simulation. Shanghai: Shanghai Science and Technology Press, 2010 (雷锦志. 系统生物学: 建模, 分析, 模拟. 上海: 上海科学技术出版社, 2010) [14] Zhou Tian-Shou. The Stochastic Dynamics of Biological Systems. Beijing: Science Press, 2009(周天寿. 生物系统的随机动力学. 北京: 科学出版社, 2009) [15] Liu Zeng-Rong, Wang Rui-Qi, Yang Ling, Zhao Xing-Ming. Construction and Analysis of Biomolecular Networks. Beijing: Science Press, 2012(刘曾荣, 王瑞琦, 杨凌, 赵兴明. 生物分子网络的构建和分析. 北京: 科学出版社, 2012) [16] Wang Pei. Modeling and Dynamical Behaviors of Several Circuits in Genetic Regulatory Networks[Ph.D. dissertation], Wuhan University, China, 2012(王沛. 几类基因调控网络环路的建模及动力学分析[博士学位论文], 武汉大学, 中国, 2012) [17] Barabási A, Gulbahce N, LoSCAlzo J. Network medicine: a network-based approach to human disease. Nature Reviews Genetics, 2011, 12(1): 56-68 [18] Smolen P, Baxter D A, Byrne J H. Modeling transcriptional control in gene networks-methods, recent results, and future directions. Bulletin of Mathematical Biology, 2000, 62(2): 247-292 [19] Jacob F, Monod J. Genetic regulatory mechanisms in the synthesis of proteins. Journal of Molecular Biology, 1961, 3(3): 318-356 [20] Monod J, Changeux J P, Jacob F. Allosteric proteins and cellular control systems. Journal of Molecular Biology, 1963, 6(4): 306-329 [21] Wiener N, Schadé J P. Progress in Biocybernetics. New York: Elsevier Publishing Company, 1966 [22] Gu Fan-Ji. Biocybernetics. Chinese Journal of Nature, 1984, 7(10): 757-760(顾凡及. 生物控制论. 自然杂志, 1984, 7(10): 757-760) [23] Wang P, Lv J H, Ogorzalek M J. Global relative parameter sensitivities of the feed-forward loops in genetic networks. Neurocomputing, 2012, 78(1): 155-165 [24] Wang P, Lv J H, Zhang Y H, Ogorzalek M J. Global relative input-output sensitivities of the feed-forward loops in genetic networks. In: Proceedings of the 31st Chinese Control Conference. Hefei, China, USA: IEEE, 2012. 7376-7381 [25] de Jong H. Modeling and simulation of genetic regulatory systems: a literature review. Journal of Computational Biology, 2002, 9(1): 67-103 [26] Li F T, Long T, Liu Y, Ouyang Q, Tang C. The yeast cell-cycle network is robustly designed. Proceedings of the National Academy of Sciences of the United States of America, 2004, 101(14): 4781-4786 [27] Wang G Y, Du C H, Chen H, Simha R, Rong Y W, Xiao Y, Zeng C. Process-based network decomposition reveals backbone motif structure. Proceedings of the National Academy of Sciences of the United States of America, 2010, 107(23): 10478-10483 [28] Davidich M I, Bornholdt S. Boolean network model predicts cell cycle sequence of fission yeast. PLoS One, 2008, 3(2): e1672 [29] Máayan A, Jenkins S L, Neves S, Hasseldine A, Grace E, Dubin-Thaler B, Eungdamrong N J, Weng G, Ram P T, Rice J J, Kershenbaum A, Stolovitzky G A, Blitzer R D, Iyengar R. Formation of regulatory patterns during signal propagation in a mammalian cellular network. Science, 2005, 309(5737): 1078-1083 [30] Glass L, Kauffman S A. The logical analysis of continuous, non-linear biochemical control networks. Journal of Theoretical Biology, 1973, 39(1): 103-129 [31] Glass L, Pasternack J S. Stable oscillations in mathematical models of biological control systems. Journal of Mathematical Biology, 1978, 6(3): 207-223 [32] Wu J L, Voit E. Hybrid modeling in biochemical systems theory by means of functional petri nets. Journal of Bioinformatics and Computational Biology, 2009, 7(1): 107-134 [33] Singhania R, Sramkoski R M, Jacobberger J W, Tyson J J. A hybrid model of mammalian cell cycle regulation. PLoS Computational Biology, 2011, 7(2): e1001077 [34] Bornholdt S. Less is more in modeling large genetic networks. Science, 2005, 310(5747): 449-451 [35] Milo R, Shen-Orr S, Itzkovitz S, Kashtan N, Chklovskii D, Alon U. Network motifs: simple building blocks of complex networks. Science, 2002, 298(5594): 824-827 [36] Shen-Orr S, Milo R, Mangan S, Alon U. Network motifs in the transcriptional regulation network of Escherichia coli. Nature Genetics, 2002, 31: 64-68 [37] Turcotte M, Garcia-Ojalvo J, SÜel G M. A genetic timer through noise-induced stabilization of an unstable state. Proceedings of the National Academy of Sciences of the United States of America, 2008, 105: 15732-15737 [38] Ghosh B, Karmakar R, Bose I. Noise characteristics of feed forward loops. Physical Biology, 2005, 2(1): 36-45 [39] Tsai T Y, Choi Y S, Ma W Z, Pomerening J R, Tang C, Ferrell J E Jr. Robust, tunable biological oscillations from interlinked positive and negative feedback loops. Science, 2008, 321(5885): 126-129 [40] Stricker J, Cookson S, Bennett M R, Mather W H, Tsimring L S, Hasty J. A fast, robust and tunable synthetic gene oscillator. Nature, 2008, 456(7221): 516-519 [41] Kim J R, Yoon Y, Cho K H. Coupled feedback loops form dynamic motifs of cellular networks. Biophysical Journal, 2008, 94(2): 359-365 [42] Wang P, LÜ J H, Zhang Y H, Ogorzalek M J. Intrinsic noise induced state transition in coupled positive and negative feedback genetic circuit. In: Proceedings of the 2011 IEEE International Conference on Systems Biology. Zhuhai, China, USA: IEEE, 2011. 356-361 [43] Zhang Z Y, Ye W M, Qian Y, Zheng Z G, Huang X H, Hu G. Chaotic motifs in gene regulatory networks. PLoS One, 2012, 7(7): e39355 [44] Marucci L, Barton D A W, Cantone I, Ricci M A, Cosma M P, Santini S, di Bernardo D, di Bernardo M. How to turn a genetic circuit into a synthetic tunable oscillator, or a bistable switch. PLoS One, 2009, 4(12): e8083 [45] Gao S, Hartman J L I V, Carter J L, Hessner M J, Wang X. Global analysis of phase locking in gene expression during cell cycle: the potential in network modeling. BMC Systems Biology, 2010, 4: 167 [46] Wu X, Wang W, Zheng W X. Inferring topologies of complex networks with hidden variables. Physical Review E, 2012, 86: 046106 [47] Mangan S, Alon U. Structure and function of the feed-forward loop network motif. Proceedings of the National Academy of Sciences of the United States of America, 2003, 100(21): 11980-11985 [48] Alon U. Network motifs: theory and experimental approaches. Nature Reviews Genetics, 2007, 8(6): 450-461 [49] Mangan S, Zaslaver A, Alon U. The coherent feedforward loop serves as a sign-sensitive delay element in transcription networks. Journal of Molecular Biology, 2003, 334(2): 197- 204 [50] Kalir S, Mangan S, Alon U. A coherent feed-forward loop with a SUM input function prolongs flagella expression in Escherichia coli. Molecular Systems Biology, 2005, 1: 0006 [51] Kittisopikul M, SÜel G M. Biological role of noise encoded in a genetic network motif. Proceedings of the National Academy of Sciences of the United States of America, 2010, 107: 13300-13305 [52] Goentoro L, Shoval O, Kirschner M W, Alon U. The incoherent feedforward loop can provide fold-change detection in gene regulation. Molecular Cell, 2009, 36(5): 894-899 [53] Prill R J, Iglesias P A, Levchenko A. Dynamic properties of network motifs contribute to biological network organization. PLoS Biology, 2005, 3: e343 [54] Ma W Z, Trusina A, EI-Samad H, Lim W A, Tang C. Defining network topologies that can achieve biochemical adaptation. Cell, 2009, 138(4): 760-773 [55] Sontag E D. Remarks on feedforward circuits, adaptation, and pulse memory. IET Systems Biology, 2010, 4(1): 39-51 [56] Chen K C, Csikasz-Nagy A, Gyorffy B, Val J, Novak B, Tyson J J. Kinetic analysis of a molecular model of the budding yeast cell cycle. Molecular Biology of the Cell, 2000, 11(1): 369-391 [57] Chen K C, Calzone L, Csikasz-Nagy A, Cross F R, Novak B, Tyson J J. Integrative analysis of cell cycle control in budding yeast. Molecular Biology of the Cell, 2004, 15(8): 3841-3862 [58] Bentele M, Eils R. Systems biology of apoptosis. Topics in Current Genetics, Vol. 13, Systems Biology: Definitions and Perspectives. Berlin: Springer-Verlag, 2005 [59] Ingalls B. Sensitivity analysis: from model parameters to system behaviour. Essays in Biochemistry, 2008, 45(1): 177 -193 [60] Khalil H K. Nonlinear Systems (3rd edition). Beijing: Publishing House of Electronics Industry, 2001. 99-102 [61] Gershenfeld N. The Nature of Mathematical Modeling. Cambridge: Cambridge University Press, 1999 [62] Mendes P, Kell D. Non-linear optimization of biochemical pathways: applications to metabolic engineering and parameter estimation. Bioinformatics, 1998, 14(10): 869-883 [63] Ye Wei-Ming, Lv Bin-Bin, Zhao Chen, Di Zeng-Ru. Control of few node genetic regulatory networks. Acta Physica Sinica, 2013, 62(1): 010507(叶纬明, 吕彬彬, 赵琛, 狄增如. 少节点基因调控网络的控制. 物理学报, 2013, 62(1): 010507) [64] Yuan Zhan-Jiang, Zhang Jia-Jun, Zhou Tian-Shou. Functions of gene autoregulatory circuits. Acta Biophysica Sinica, 2010, 26(6): 457-471(苑占江, 张家军, 周天寿. 基因自调控环路的功能. 生物物理学报, 2010, 26(6): 457-471) [65] Freund J A, Pöschel T. Stochastic Processes in Physics, Chemistry, and Biology. Berlin: Springer-Verlag, 2000 [66] Gardner T S, Cantor C R, Collins J J. Construction of a genetic toggle switch in Escherichia coli. Nature, 2000, 403(6767): 339-342 [67] Wan L, Zhou Q H, Wang P. Ultimate boundedness of stochastic Hopfield neural networks with time-varying delays. Neurocomputing, 2011, 74(17): 2967-2971 [68] Wan L, Zhou Q H, Wang P. Ultimate boundedness and an attractor for stochastic Hopfield neural networks with time-varying delays. Nonlinear Analysis: Real World Applications, 2012, 13(2): 953-958 [69] Zhou T S, Zhang J J, Yuan Z J, Xu A L. External stimuli mediate collective rhythms: artificial control strategies. PLoS One, 2007, 2: e231 [70] Kuznetsov A, Kaern M, Kopell N. Synchrony in a population of hysteresis-based genetic oscillators. SIAM Journal on Applied Mathematics, 2004, 65(2): 392-425 [71] Wan L, Zhou Q H, Wang P. Weak attractor for stochastic Cohen-Grossberg neural networks with delays. Nonlinear Dynamics, 2012, 67(3): 1753-1759 [72] Raser J M, O'Shea E K. Control of stochasticity in Eukaryotic gene expression. Science, 2004, 304(5678): 1811-1814 [73] Nakao H, Arai K, Kawamura Y. Noise-induced synchronization and clustering in ensembles of uncoupled limit-cycle oscillations. Physical Review Letters, 2007, 98(18): 184101 [74] Xiong W, Ferrell J E Jr. A positive-feedback-based bistable ''memory module'' that governs a cell fate decision. Nature, 2003, 426(6965): 460-465 [75] Tian T, Burrage K. Stochastic models for regulatory networks of the genetic toggle switch. Proceedings of the National Academy of Sciences of the United States of America, 2006, 103(22): 8372-8377 [76] Wang J W, Zhang J J, Yuan Z J, Zhou T S. Noise-induced switches in network systems of the genetic toggle switch. BMC Systems Biology, 2007, 1(1): 50 [77] Zhang Jia-Jun, Wang Jun-Wei, Yuan Zhan-Jiang, Zhou Tian-Shou. Noise-induced synchronized switching of a multicellular system. Progress in Biochemistry and Biophysics, 2008, 35(8): 929-939(张家军, 王军威, 苑占江, 周天寿. 噪声诱导多细胞系统的同步切换. 生物化学与生物物理进展, 2008, 35(8): 929-939) [78] Loinger A, Lipshtat A, Balaban N Q, Biham O. Stochastic simulations of genetic switch systems. Physical Review E, 2007, 75(2): 021904 [79] Rosenfeld N, Young J W, Alon U, Swain P S, Elowitz M B. Gene regulation at the single-cell level. Science, 2005, 307(5717): 1962-1965 [80] Shahrezaei V, Ollivier J F, Swain P S. Colored extrinsic fluctuations and stochastic gene expression. Molecular Systems Biology, 2008, 4: 196 [81] Wang P, Lv J H, Maciej O J. Synchronized switching induced by colored noise in the genetic toggle switch systems coupled by quorum sensing mechanism. In: Proceedings of the 30th Chinese Control Conference. Yantai, China, USA: IEEE, 2011. 6605-6609 [82] Plahte E, Mestl T, Omholt S W. Feedback loops, stability and multistationarity in dynamical systems. Journal of Biological Systems, 1995, 3(2): 409-414 [83] Snoussi E H. Necessary conditions for multistationarity and stable periodicity. Journal of Biological Systems, 1998, 6(1): 3-9 [84] Shibata T, Fujimoto K. Noisy signal amplification in ultrasensitive signal transduction. Proceedings of the National Academy of Sciences of the United States of America, 2005, 102(2): 331-336 [85] Hornung G, Barkai N. Noise propagation and signaling sensitivity in biological networks: a role for positive feedback. PLoS Computational Biology, 2008, 4: e8 [86] Tian X J, Zhang X P, Liu F, Wang W. Interlinking positive and negative feedback loops creates a tunable motif in gene regulatory networks. Physical Review E, 2009, 80: 011926 [87] Hasty J, Dolnik M, Rottscháfer V, Collins J J. Synthetic gene network for entraining and amplifying cellular oscillations. Physical Review Letters, 2002, 88: 148101 [88] Song H, Smolen P, Av-Ron E, Baxter D A, Byrne J H. Dynamics of a minimal model of interlocked positive and negative feedback loops of transcriptional regulation by cAMP-response element binding proteins. Biophysical Journal, 2007, 92(10): 3407-3424 [89] Wang P, Lv J, Wan L, Chen Y. A stochastic simulation algorithm for biochemical reactions with delays. In: Proceedings of the 2013 IEEE International Conference on Systems Biology. Huangshan, China, USA: IEEE, 2013. 109-114 [90] Brandman O, Ferrell J E Jr, Li R, Meyer T. Interlinked fast and slow positive feedback loops drive reliable cell decisions. Science, 2005, 310(5747): 496-498 [91] Zhang X P, Cheng Z, Liu F, Wang W. Linking fast and slow positive feedback loops creates an optimal bistable switch in cell signaling. Physical Review E, 2007, 76: 031924 [92] Sriram K, Soliman S, Fages F. Dynamics of the interlocked positive feedback loops explaining the robust epigenetic switching in Candida albicans. Journal of Theoretical Biology, 2009, 258(1): 71-88 [93] Smolen P, Baxter D A, Byrne J H. Interlinked dual-time feedback loops can enhance robustness to stochasticity and persistence of memory. Physical Review E, 2009, 79: 031902 [94] Wang P, Zhang Y, Lv J, Yu X. Functional characteristics of additional positive feedback in genetic circuits. Communications in Nonlinear Science and Numerical Simulation, submitted, 2013 [95] Kobayashi Y, Shibata T, Kuramoto Y, Mikhailov A S. Robust network clocks: design of genetic oscillators as a complex combinatorial optimization problem. Physical Review E, 2011, 83: 060901 [96] Mondragón-Palomino O, Danino T, Selimkhanov J, Tsimring L, Hasty J. Entrainment of a population of synthetic genetic oscillators. Science, 2011, 333(6074): 1315-1319 [97] Zhao Yan, Wang Ting-Huai. Cybernetics and entropy theory in the biofeedback therapy. Chinese Journal of Practical Nervous Diseases, 2009, 12(13): 41-44(赵妍, 王庭槐. 生物反馈治疗中的控制论和熵原理. 中国实用神经疾病杂志, 2009, 12(13): 41-44) [98] Russo G, Slotine J J E. Global convergence of quorum-sensing networks. Physical Review E, 2010, 82: 041919 [99] Stankovski T, Duggento A, McClintock P V E, Stefanovska A. Inference of time-evolving coupled dynamical systems in the presence of noise. Physical Review Letters, 2012, 109: 024101 [100] Chen Guan-Rong. Problems and challenges in control theory under complex dynamical network environments. Acta Automatica Sinica, 2013, 39(4): 312-321(陈关荣. 复杂动态网络环境下控制理论遇到的问题与挑战. 自动化学报, 2013, 39(4): 312-321) [101] Lu Bao-Yun, Yue Hong, Developing objective sensitivity analysis of periodic systems: case studies of biological oscillators. Acta Automatica Sinica, 2012, 38(7): 1065-1073 [102] Furusawa C, Kaneko K. Chaotic expression dynamics implies pluripotency: when theory and experiment meet. Biology Direct, 2009, 4: 17 [103] Wang P, Lu R Q, Chen Y, Wu X Q. Hybrid modelling of the general middle-sized genetic regulatory networks. In: Proceedings of the 2013 IEEE International Symposium on Circuits and Systems. Beijing, China, USA: IEEE, 2013. 2103-2106 [104] He L, Hannon G J. MicroRNAs: small RNAs with a big role in gene regulation. Nature Reviews Genetics, 2004, 5(7): 522-531 [105] Pan Wei. Analysis and Control of Genetic Regulatory Networks[Master dissertation], University of Science and Technology of China, China, 2011(潘为. 基因调控网络的分析与控制[硕士学位论文], 中国科学技术大学, 中国, 2011) [106] Cheng A A, Lu T K. Synthetic biology: an emerging engineering discipline. Annual Review of Biomedical Engineering, 2012, 14: 155-178
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