Identifiability and Reconstruction of Biochemical Reaction Networks from Population Snapshot Data
Abstract
1. Introduction
2. Modelling of Biochemical Reaction Networks
2.1. Vector Representation of Moment Equations
2.2. Input–Output Model
3. Identification of Parameters
3.1. Structural Identifiability
- (a)
- locally identifiable atif, for some neighborhoodof,
- (b)
- globally identifiable atif the implication above holds for.
3.2. Parameter Identification in Practice
3.3. Example: Reporter Gene Expression Dynamics
4. Identification of Networks
4.1. Step 1: Identifiability of a Linear Model for the Moment Dynamics
- Case (i):
- Observation of mean only (). In this case, and , with nonsingular (typically the identity). In view of the structure of A in (5), for this definition of C, one realization of (10) and (11) isThis realization is of order and is minimal for non-degenerate definitions of S, W and G. Assumption 1 is thus satisfied provided the input and/or the initial conditions excite all system dynamics. Then, any reconstructed model must satisfy for some invertible T. Since is known and invertible, is uniquely determined, and so are and .
- Case (ii):
- Observation of mean and covariance matrix (). Since , this case is captured by a model where C has rows and columns. The definition of C is such that , where is an -dimensional vector containing all and only the distinct entries of z, and is invertible (in particular, C and can be -matrices). One realization of (10) and (11) is then
4.2. Step 2: Identifiability of the Network Stoichiometry and Rate Parameter Matrices
Algorithm 1: Identification of stoichiometry and rate parameters from a model of the moment dynamics |
Given and an : |
Set ; |
For every : |
Solve problem (28) to get and the solution set ; |
If , include in ; |
Return . |
4.3. Network Identification in Practice
4.4. Example: A Toy Network
5. Discussion
Funding
Conflicts of Interest
References
- Ashyraliyev, M.; Fomekong-Nanfack, Y.; Kaandorp, J.; Blom, J. Systems Biology: Parameter Estimation for Biochemical Models. FEBS J. 2009, 276, 886–902. [Google Scholar] [CrossRef] [PubMed]
- Marbach, D.; Costello, J.; Küffner, R.; Vega, N.; Prill, R.; Camacho, D.; Allison, K.; The DREAM5 Consortium; Kellis, M.; Collins, J.; et al. Wisdom of crowds for robust gene network inference. Nat. Methods 2012, 9, 796–804. [Google Scholar] [CrossRef] [PubMed]
- Purnick, P.; Weiss, R. The second wave of synthetic biology: From modules to systems. Nat. Rev. Mol. Cell Biol. 2009, 10, 410–422. [Google Scholar] [CrossRef] [PubMed]
- Chis, O.T.; Banga, J.R.; Balsa-Canto, E. Structural Identifiability of Systems Biology Models: A Critical Comparison of Methods. PLoS ONE 2011, 6, e27755. [Google Scholar] [CrossRef] [PubMed]
- Gutenkunst, R.N.; Waterfall, J.J.; Casey, F.P.; Brown, K.S.; Myers, C.R.; Sethna, J.P. Universally Sloppy Parameter Sensitivities in Systems Biology Models. PLoS Comput. Biol. 2007, 3, e189. [Google Scholar] [CrossRef] [PubMed]
- Raue, A.; Kreutz, C.; Maiwald, T.; Bachmann, J.; Schilling, M.; Klingmüller, U.; Timmer, J. Structural and practical identifiability analysis of partially observed dynamical models by exploiting the profile likelihood. Bioinformatics 2009, 25, 1923–1929. [Google Scholar] [CrossRef] [PubMed]
- Taniguchi, Y.; Choi, P.J.; Li, G.W.; Chen, H.; Babu, M.; Hearn, J.; Emili, A.; Xie, X.S. Quantifying E. coli proteome and transcriptome with single-molecule sensitivity in single cells. Science 2010, 329, 533–538. [Google Scholar] [CrossRef] [PubMed]
- Munsky, B.; Trinh, B.; Khammash, M. Listening to the noise: Random fluctuations reveal gene network parameters. Mol. Syst. Biol. 2009, 5, 318. [Google Scholar] [CrossRef] [PubMed]
- Zechner, C.; Ruess, J.; Krenn, P.; Pelet, S.; Peter, M.; Lygeros, J.; Koeppl, H. Moment-based inference predicts bimodality in transient gene expression. PNAS 2012, 109, 8340–8345. [Google Scholar] [CrossRef] [PubMed]
- Helmke, U.; Hüper, K.; Khammash, M. Global identifiability of a simple linear model for gene expression analysis. In Proceedings of the 52nd IEEE CDC, Florence, Italy, 10–13 December 2013. [Google Scholar]
- Cho, K.H.; Choo, S.M.; Jung, S.; Kim, J.R.; Choi, H.S.; Kim, J. Reverse engineering of gene regulatory networks. IET Syst. Biol. 2007, 1, 149–163. [Google Scholar] [CrossRef] [PubMed]
- Markowetz, F.; Spang, R. Inferring cellular networks: A review. BMC Bioinform. 2007, 28, S5. [Google Scholar] [CrossRef] [PubMed]
- Hasenauer, J.; Waldherr, S.; Doszczak, M.; Radde, N.; Scheurich, P.; Allgower, F. Identification of models of heterogeneous cell populations from population snapshot data. BMC Bioinform. 2011, 12, 125. [Google Scholar] [CrossRef] [PubMed]
- Paulsson, J. Models of stochastic gene expression. Phys. Life Rev. 2005, 2, 157–175. [Google Scholar] [CrossRef]
- Thattai, M.; van Oudenaarden, A. Intrinsic noise in gene regulatory networks. PNAS 2001, 98, 8614–8619. [Google Scholar] [CrossRef] [PubMed]
- Hespanha, J. Modelling and analysis of stochastic hybrid systems. IEE Proc. Control Theory Appl. 2006, 153, 520–535. [Google Scholar] [CrossRef]
- Sotiropoulos, V.; Kaznessis, Y. Analytical Derivation of Moment Equations in Stochastic Chemical Kinetics. Chem. Eng. Sci. 2011, 66, 268–277. [Google Scholar] [CrossRef] [PubMed]
- Cinquemani, E. Reconstruction of promoter activity statistics from reporter protein population snapshot data. In Proceedings of the 54th IEEE CDC, Osaka, Japan, 15–18 December 2015; pp. 1471–1476. [Google Scholar]
- Cinquemani, E. Structural identification of biochemical reaction networks from population snapshot data. In Proceedings of the 20th IFAC World Congress, IFAC—PapersOnLine, Toulouse, France, 9–14 July 2017; Volume 50, pp. 12629–12634. [Google Scholar]
- Berthoumieux, S.; Brilli, M.; Kahn, D.; de Jong, H.; Cinquemani, E. On the identifiability of metabolic network models. J. Math. Biol. 2013, 67, 1795–1832. [Google Scholar] [CrossRef] [PubMed]
- Bansal, M.; Belcastro, V.; Ambesi-Impiombato, A.; di Bernardo, D. How to infer gene networks from expression profiles. Mol. Syst. Biol. 2007, 3, 78. [Google Scholar] [CrossRef] [PubMed]
- Gardner, T.; Faith, J. Reverse-engineering transcription control networks. Phys. Life Rev. 2005, 2, 65–88. [Google Scholar] [CrossRef] [PubMed]
- Porreca, R.; Cinquemani, E.; Lygeros, J.; Ferrari-Trecate, G. Identification of genetic network dynamics with unate structure. Bioinformatics 2010, 26, 1239–1245. [Google Scholar] [CrossRef] [PubMed]
- Neuert, G.; Munsky, B.; Tan, R.; Teytelman, L.; Khammash, M.; van Oudenaarden, A. Systematic Identification of Signal-Activated Stochastic Gene Regulation. Science 2013, 339, 584–587. [Google Scholar] [CrossRef] [PubMed]
- Gillespie, D. A Rigorous Derivation of the Chemical Master Equation. Physica A 1992, 188, 404–425. [Google Scholar] [CrossRef]
- Van Kampen, N. Stochastic Processes in Physics and Chemistry; North-Holland Personal Library: Amsterdam, The Netherlands, 1992. [Google Scholar]
- Gadgil, C.; Lee, C.; Othmer, H. A stochastic analysis of first-order reaction networks. Bull. Math. Biol. 2005, 67, 901–946. [Google Scholar] [CrossRef] [PubMed]
- Gillespie, D.T. The chemical Langevin equation. J. Chem. Phys. 2000, 113, 297–306. [Google Scholar] [CrossRef]
- Gillespie, C. Moment-closure approximations for mass-action models. IET Syst. Biol. 2009, 3, 52–58. [Google Scholar] [CrossRef] [PubMed]
- Parise, F.; Ruess, J.; Lygeros, J. Grey-box techniques for the identification of a controlled gene expression model. In Proceedings of the ECC, Strasbourg, France, 24–27 June 2014. [Google Scholar]
- Walter, E.; Pronzato, L. Identification of Parametric Models—From Experimental Data; Springer: London, UK, 1997. [Google Scholar]
- Walter, E. (Ed.) Identifiability of Parametric Models; Pergamon Press: Oxford, UK, 1987. [Google Scholar]
- Khalil, H.K. Nonlinear Systems; Prentice Hall: Upper Saddle River, NJ, USA, 2002. [Google Scholar]
- Ruess, J.; Lygeros, J. Identifying stochastic biochemical networks from single-cell population experiments: A comparison of approaches based on the Fisher information. In Proceedings of the 52nd IEEE CDC, Florence, Italy, 10–13 December 2013; pp. 2703–2708. [Google Scholar]
- Kay, S.M. Fundamentals of Statistical Signal Processing [Volume I] Estimation Theory; Prentice Hall: Upper Saddle River, NJ, USA, 1993; p. 1. [Google Scholar]
- De Jong, H.; Ranquet, C.; Ropers, D.; Pinel, C.; Geiselmann, J. Experimental and computational validation of models of fluorescent and luminescent reporter genes in bacteria. BMC Syst. Biol. 2010, 4, 55. [Google Scholar] [CrossRef] [PubMed]
- Kaern, M.; Elston, T.C.; Blake, W.J.; Collins, J.J. Stochasticity in gene expression: From theories to phenotypes. Nat. Rev. Gen. 2005, 6, 451–464. [Google Scholar] [CrossRef] [PubMed]
- Sanft, K.R.; Wu, S.; Roh, M.; Fu, J.; Lim, R.K.; Petzold, L.R. StochKit2: Software for discrete stochastic simulation of biochemical systems with events. Bioinformatics 2011, 27, 2457–2458. [Google Scholar] [CrossRef] [PubMed]
- Ljung, L. System Identification: Theory for the User; Prentice Hall: Upper Saddle River, NJ, USA, 1999. [Google Scholar]
- Callier, F.; Desoer, C. Linear System Theory; Springer: New York, NY, USA, 1991. [Google Scholar]
- Boyd, S.; Vandenberghe, L. Convex Optimization; Cambridge University Press: New York, NY, USA, 2004. [Google Scholar]
- Singh, A.; Hespanha, J. Approximate Moment Dynamics for Chemically Reacting Systems. IEEE Trans. Autom. Control 2011, 56, 414–418. [Google Scholar] [CrossRef]
- Ruess, J.; Milias-Argeitis, A.; Summers, S.; Lygeros, J. Moment estimation for chemically reacting systems by extended Kalman filtering. J. Chem. Phys. 2011, 135, 165102. [Google Scholar] [CrossRef] [PubMed]
m | 1 | 2 | 3 | 4 | |
---|---|---|---|---|---|
Case (i) | Number of solutions | 0 | 4 | ||
Acceptance ratio | |||||
Computational time | < | ||||
Case (ii) | Number of solutions | 0 | 0 | 564 | |
Acceptance ratio | |||||
Computational time |
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Cinquemani, E. Identifiability and Reconstruction of Biochemical Reaction Networks from Population Snapshot Data. Processes 2018, 6, 136. https://doi.org/10.3390/pr6090136
Cinquemani E. Identifiability and Reconstruction of Biochemical Reaction Networks from Population Snapshot Data. Processes. 2018; 6(9):136. https://doi.org/10.3390/pr6090136
Chicago/Turabian StyleCinquemani, Eugenio. 2018. "Identifiability and Reconstruction of Biochemical Reaction Networks from Population Snapshot Data" Processes 6, no. 9: 136. https://doi.org/10.3390/pr6090136
APA StyleCinquemani, E. (2018). Identifiability and Reconstruction of Biochemical Reaction Networks from Population Snapshot Data. Processes, 6(9), 136. https://doi.org/10.3390/pr6090136