Structurally robust biological networks

BackgroundThe molecular circuitry of living organisms performs remarkably robust regulatory tasks, despite the often intrinsic variability of its components. A large body of research has in fact highlighted that robustness is often a structural property of biological systems. However, there are few systematic methods to mathematically model and describe structural robustness. With a few exceptions, numerical studies are often the preferred approach to this type of investigation.ResultsIn this paper, we propose a framework to analyze robust stability of equilibria in biological networks. We employ Lyapunov and invariant sets theory, focusing on the structure of ordinary differential equation models. Without resorting to extensive numerical simulations, often necessary to explore the behavior of a model in its parameter space, we provide rigorous proofs of robust stability of known bio-molecular networks. Our results are in line with existing literature.ConclusionsThe impact of our results is twofold: on the one hand, we highlight that classical and simple control theory methods are extremely useful to characterize the behavior of biological networks analytically. On the other hand, we are able to demonstrate that some biological networks are robust thanks to their structure and some qualitative properties of the interactions, regardless of the specific values of their parameters.

[1]  Liang Qiao,et al.  Bistability and Oscillations in the Huang-Ferrell Model of MAPK Signaling , 2007, PLoS Comput. Biol..

[2]  M. Mackey,et al.  Dynamics and bistability in a reduced model of the lac operon. , 2004, Chaos.

[3]  Hidde de Jong,et al.  Modeling and Simulation of Genetic Regulatory Systems: A Literature Review , 2002, J. Comput. Biol..

[4]  N. Wingreen,et al.  A quantitative comparison of sRNA-based and protein-based gene regulation , 2008, Molecular systems biology.

[5]  Alexander N Gorban,et al.  Dynamical robustness of biological networks with hierarchical distribution of time scales. , 2007, IET systems biology.

[6]  Douglas B. Kell,et al.  Deterministic mathematical models of the cAMP pathway in Saccharomyces cerevisiae , 2009, BMC Systems Biology.

[7]  Franco Blanchini,et al.  Set invariance in control , 1999, Autom..

[8]  Chi-Ying F. Huang,et al.  Ultrasensitivity in the mitogen-activated protein kinase cascade. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[9]  James E Ferrell,et al.  Simple, realistic models of complex biological processes: Positive feedback and bistability in a cell fate switch and a cell cycle oscillator , 2009, FEBS letters.

[10]  Franco Blanchini,et al.  Set-theoretic methods in control , 2007 .

[11]  M. Feinberg,et al.  Structural Sources of Robustness in Biochemical Reaction Networks , 2010, Science.

[12]  Uri Alon,et al.  Input–output robustness in simple bacterial signaling systems , 2007, Proceedings of the National Academy of Sciences.

[13]  K. Sneppen,et al.  Dynamic features of gene expression control by small regulatory RNAs , 2009, Proceedings of the National Academy of Sciences.

[14]  M. Feinberg Chemical reaction network structure and the stability of complex isothermal reactors—I. The deficiency zero and deficiency one theorems , 1987 .

[15]  Tianhai Tian,et al.  Robustness of mathematical models for biological systems , 2004 .

[16]  T. Hwa,et al.  Quantitative Characteristics of Gene Regulation by Small RNA , 2007, PLoS Biology.

[17]  Eduardo D. Sontag,et al.  Monotone and near-monotone biochemical networks , 2007, Systems and Synthetic Biology.

[18]  J. Bodart,et al.  On the equilibria of the MAPK cascade: Cooperativity, modularity and bistability , 2007, q-bio/0702051.

[19]  J E Ferrell,et al.  The biochemical basis of an all-or-none cell fate switch in Xenopus oocytes. , 1998, Science.

[20]  U. Alon,et al.  Robustness in bacterial chemotaxis , 2022 .

[21]  Ashish Tiwari,et al.  Box invariance for biologically-inspired dynamical systems , 2007, 2007 46th IEEE Conference on Decision and Control.

[22]  B. Kholodenko,et al.  Signaling switches and bistability arising from multisite phosphorylation in protein kinase cascades , 2004, The Journal of cell biology.

[23]  M. Mackey,et al.  Feedback regulation in the lactose operon: a mathematical modeling study and comparison with experimental data. , 2003, Biophysical journal.

[24]  S. Leibler,et al.  Robustness in simple biochemical networks , 1997, Nature.

[25]  Olaf Wolkenhauer,et al.  Principal difference between stability and structural stability (robustness) as used in systems biology. , 2007, Nonlinear dynamics, psychology, and life sciences.

[26]  N. Rouche,et al.  Stability Theory by Liapunov's Direct Method , 1977 .

[27]  H. Kitano Systems Biology: A Brief Overview , 2002, Science.

[28]  J. Doyle,et al.  Robust perfect adaptation in bacterial chemotaxis through integral feedback control. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[29]  Kwang-Hyun Cho,et al.  Quantitative analysis of robustness and fragility in biological networks based on feedback dynamics , 2008, Bioinform..

[30]  Antonis Papachristodoulou,et al.  Advanced Methods and Algorithms for Biological Networks Analysis , 2006, Proceedings of the IEEE.

[31]  Nicole Radde,et al.  Graphical methods for analysing feedback in biological networks – A survey , 2010, Int. J. Syst. Sci..

[32]  Eduardo Sontag,et al.  Untangling the wires: A strategy to trace functional interactions in signaling and gene networks , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[33]  F. Jacob,et al.  L'opéron : groupe de gènes à expression coordonnée par un opérateur [C. R. Acad. Sci. Paris 250 (1960) 1727–1729] , 2005 .

[34]  Yamir Moreno,et al.  On the robustness of complex heterogeneous gene expression networks. , 2005, Biophysical chemistry.

[35]  S. Mangan,et al.  The coherent feedforward loop serves as a sign-sensitive delay element in transcription networks. , 2003, Journal of molecular biology.

[36]  John A. Jacquez,et al.  Qualitative Theory of Compartmental Systems , 1993, SIAM Rev..

[37]  Jose M. G. Vilar,et al.  Modeling network dynamics: the lac operon, a case study , 2004 .

[38]  Oliver Ebenhöh,et al.  Ground State Robustness as an Evolutionary Design Principle in Signaling Networks , 2009, PloS one.

[39]  W. Lim,et al.  Defining Network Topologies that Can Achieve Biochemical Adaptation , 2009, Cell.

[40]  Andre Levchenko,et al.  Dynamic Properties of Network Motifs Contribute to Biological Network Organization , 2005, PLoS biology.

[41]  P. Cluzel,et al.  A natural class of robust networks , 2003, Proceedings of the National Academy of Sciences of the United States of America.