Biochemical Reaction Network

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Relative Degree Two MIMO Nonlinear System:

Model description: 

Consider the following relative degree two MIMO nonlinear systems:

$$\begin{align*} \dot x_1 &= x_2 + \vartheta _1 x_1 \sin \left(t \right) + \Delta _1 \left({x_1 } \right) \\ \dot x_2 &= u + \vartheta _2 \left[{\matrix{{\left({x_1 + x_{2,1} } \right)\sin ^3 \left(t \right)} \cr {x_{2,1} + 2x_{2,2} } \cr}} \right] + \left[{\matrix{1 \cr {x_1 + x_{2,2} } \cr}} \right]\Delta _2 \left({x_{2,1} } \right) \\ y &= \left[{x_1,x_{2,2} } \right]^{\mathrm T}, \end{align*}$$

where $\Delta_1(x_1)=d_1\sin{(r_1x_1)}$ and $\Delta_2(x_{2,1})=d_2\tan{(r_2,x_{2,1})}.$ $\vartheta_1, \vartheta_2,\Delta_1,\Delta_2$ satisfy

$\displaylines{2 \le \vartheta _1 \le 4, - 4 \le \vartheta _2 \le - 1, \left\vert {\Delta _1 \left({x_1 } \right)} \right\vert \le \delta _1 = 40\cr \left\vert {\Delta _2 \left({x_{2,1} } \right)} \right\vert \le \delta _2 = 20. }$

The initial conditions are assumed to be $x_1(0)=0.5,x_{2,1}(0)=0$ and $x_{2,2}(0)=0.2$.

The actual plant parameters are

$\theta _1 = 3$, $\theta _2 = - 3$, $d_1 = - 30$, $d_2 = - 15$, $r_1 = 2$, $r_2 = 0.05.$

Type: 

Form: 

Time domain: 

Linearity: 

Publication details: 

TitleRobust Adaptive Fuzzy Control by Backstepping for a Class of MIMO Nonlinear Systems
Publication TypeJournal Article
Year of Publication2010
AuthorsLee, Hyeongcheol
JournalIEEE Transactions on Fuzzy Systems
Volume19
Issue2
Pagination265 - 275
Date Published11/2010
ISSN1063-6706
Accession Number11903670
Keywordsadaptive control, feedback, fuzzy control, MIMO systems, nonlinear control systems, robust control
AbstractThis paper presents a robust adaptive control method for a class of multi-input-multi-output (MIMO) nonlinear systems that are transformable to a parametric-strict-feedback form which has couplings among input channels and the appearance of parametric uncertainties in the input matrices. The proposed approach effectively combines the design techniques of robust adaptive control by backstepping and adaptive fuzzy-logic control in order to remove the matching-condition requirement and to provide boundedness of tracking errors, even under dominant model uncertainties and poor parameter adaptation. Unlike previous robust adaptive fuzzy controls of MIMO nonlinear systems, this research introduces the robustness terms explicitly in the controller structure to counteract the effects of model uncertainties and parameter-adaptation errors. Uniform boundedness of the MIMO nonlinear control system is proved, and simulation results further validate the effectiveness and performance of the proposed control method.
DOI10.1109/TFUZZ.2010.2095859

NF$\kappa$B model

Model description: 

The model of the NF$\kappa$B regulatory module, as proposed by Lipniacki et al, is characterised by two compartment kinetics of the activators $IKK$ and $NF-kB$, the inhibitors $A20$ and $IkB\alpha$, and their complexes. The model is described by the differential system:

$$\begin{align*} \dot{x}_1 &= k_{prod}-k_{deg}x_1 - k_1x_1u(t),\\ \dot{x}_2 &= -k_3x_2 - k_{deg}x_2 - a_2x_2x_{10}+t_1x_4 - a_3x_2x_{13} + t_2x_5 + (k_1x_1 - k_2x_2x_8)u(t),\\ \dot{x}_3 &= k_3x_2 - k_{deg}x_3+k_2x_2x_8u(t),\\ \dot{x}_4 &= a_2x_2x_{10}-t_1x_4,\\ \dot{x}_5 &= a_3x_2x_{13}-t_2x_5,\\ \dot{x}_6 &= c_{6a}x_{13}-a_1x_6x_{10}+t_2x_5-i_1x_6,\\ \dot{x}_7 &= i_1kvx_6-a_1x_{11}x_7,\\ \dot{x}_8 &= c_4x_9-c_5x_8,\\ \dot{x}_9 &= c_2+c_1x_7-c_3x_9,\\ \dot{x}_{10} &= -a_2x_2x_{10}-a_1x_{10}x_6 + c_{4a}x_{12} - c_{5a}x_{10}-i_{1a}x_{10}+e_{1a}x_{11},\\ \dot{x}_{11} &= -a_1x_{11}x_7+i_{1a}kvx_{10}-e_{1a}kvx_{11},\\ \dot{x}_{12} &= c_{2a}+c_{1a}x_7 - c_{3a}x_{12},\\ \dot{x}_{13} &= a_1x_{10}x_6 - c_{6a}x_{13}-a_3x_2x_{13}+e_{2a}x_{14},\\ \dot{x}_{14} &= a_1x_{11}x_7 - e_{2a}kvx_{14},\\ \dot{x}_{15} &= c_{2c}+c_{1c}x_7 - c_{3c}x_{15}.\\ \end{align*}$$

In their paper, Lipniacki et al. fixed some of the model parameters by using values from the literature. In order to assign values to the following unknown parameters:

$\mathbf{p}=[t_1,t_2,c_{3a},c_{4a},c_5,k_1,k_2,k_3,k_{prod},k_{deg},i_1,e_{2a},i_{1a}]^{\mathrm T}.$

They used experimental data from previous works by Lee et al. and Hoffmann et al which corresponds to the observation of $y_1=x_7,$ $y_2=x_{10} + x_{13},$ $y_3=x_9,$ $y_4=x_1+x_2+x_3,$ $y_5=x_2,$ $y_6=x_{12}$.

Type: 

Form: 

Model order: 

15

Time domain: 

Linearity: 

Publication details: 

TitleStructural Identifiability of Systems Biology Models: A Critical Comparison of Methods
Publication TypeJournal Article
Year of Publication2011
AuthorsChis, Oana-Teodora, Banga Julio R., and Balsa-Canto Eva
Secondary AuthorsJaeger, JohannesEditor
JournalPLoS ONE
Volume6
Start Page1
Issue11
Pagination1-16
Date Published10/2011
ISSN1932-6203
AbstractAnalysing the properties of a biological system through in silico experimentation requires a satisfactory mathematical representation of the system including accurate values of the model parameters. Fortunately, modern experimental techniques allow obtaining time-series data of appropriate quality which may then be used to estimate unknown parameters. However, in many cases, a subset of those parameters may not be uniquely estimated, independently of the experimental data available or the numerical techniques used for estimation. This lack of identifiability is related to the structure of the model, i.e. the system dynamics plus the observation function. Despite the interest in knowing a priori whether there is any chance of uniquely estimating all model unknown parameters, the structural identifiability analysis for general non-linear dynamic models is still an open question. There is no method amenable to every model, thus at some point we have to face the selection of one of the possibilities. This work presents a critical comparison of the currently available techniques. To this end, we perform the structural identifiability analysis of a collection of biological models. The results reveal that the generating series approach, in combination with identifiability tableaus, offers the most advantageous compromise among range of applicability, computational complexity and information provided.
DOI10.1371/journal.pone.0027755

Arabidopsis Thaliana Model (2)

Model description: 

This is a pure polynomial form of the model given in the Arabidopsis Thaliana Model (1):

$$\begin{align*} \dot{x}_1 &= n_1x_6x_8 - m_1x_1x_9 + q_1x_7u(t), \\ \dot{x}_2 &= p_1x_1 - r_1x_2 + r_2x_3 - m_2x_2x_{10},\\ \dot{x}_3 &= r_1x_2 - r_2x_3 - m_3x_3x_{11},\\ \dot{x}_4 &= n_2g_2^2x_{12} - m_4x_4x_{13},\\ \dot{x}_5 &= p_2x_4 - r_3x_5 + r_4x_6 - m_5x_5x{14},\\ \dot{x}_6 &= r_3x_5 - r_4x_6-m_6x_6x_{15},\\ \dot{x}_7 &= p_3-m_7x_7x_{16} - (p_3 + q_2x_7)u(t),\\ \dot{x}_8 &= -\dot{x}_6x_8^2,\\ \dot{x}_9 &= -\dot{x}_1x_9^2,\\ \dot{x}_{10} &= -\dot{x}_2x_{10}^2,\\ \dot{x}_{11} &= -\dot{x}_3x_{11}^2,\\ \dot{x}_{12} &= -2x_3\dot{x}_3x_{12}^2,\\ \dot{x}_{13} &= -\dot{x}_4x_{13}^2,\\ \dot{x}_{14} &= -\dot{x}_5x_{14}^2,\\ \dot{x}_{15} &= -\dot{x}_6x_{15}^2,\\ \dot{x}_{16} &= -\dot{x}_7x_{16}^2, \\ x_0(p)&=\left(0,0,0,0,0,0,0,\dfrac{1}{g_1},\dfrac{1}{k_1},\dfrac{1}{k_2},\dfrac{1}{k_3},\dfrac{1}{g_1^2},\dfrac{1}{k_4},\dfrac{1}{k_5},\dfrac{1}{k_6},\dfrac{1}{k_7}\right). \end{align*}$$

Type: 

Form: 

Model order: 

16

Time domain: 

Publication details: 

TitleStructural Identifiability of Systems Biology Models: A Critical Comparison of Methods
Publication TypeJournal Article
Year of Publication2011
AuthorsChis, Oana-Teodora, Banga Julio R., and Balsa-Canto Eva
Secondary AuthorsJaeger, JohannesEditor
JournalPLoS ONE
Volume6
Start Page1
Issue11
Pagination1-16
Date Published10/2011
ISSN1932-6203
AbstractAnalysing the properties of a biological system through in silico experimentation requires a satisfactory mathematical representation of the system including accurate values of the model parameters. Fortunately, modern experimental techniques allow obtaining time-series data of appropriate quality which may then be used to estimate unknown parameters. However, in many cases, a subset of those parameters may not be uniquely estimated, independently of the experimental data available or the numerical techniques used for estimation. This lack of identifiability is related to the structure of the model, i.e. the system dynamics plus the observation function. Despite the interest in knowing a priori whether there is any chance of uniquely estimating all model unknown parameters, the structural identifiability analysis for general non-linear dynamic models is still an open question. There is no method amenable to every model, thus at some point we have to face the selection of one of the possibilities. This work presents a critical comparison of the currently available techniques. To this end, we perform the structural identifiability analysis of a collection of biological models. The results reveal that the generating series approach, in combination with identifiability tableaus, offers the most advantageous compromise among range of applicability, computational complexity and information provided.
DOI10.1371/journal.pone.0027755

Arabidopsis Thaliana Model (1)

Model description: 

The model describes the first multi-gene loop identified in the Arabidopsis circadian clock that comprises a negative feedback loop, in which two partially redundant genes, Late Elongated Hypocotyl (LHY) and Circadian Clock Associated 1 (CCA1), repress the expression of their activator, Timing of CAB Expression 1 (TOC1). A minimal mathematical representation of the system requires 7 coupled differential equations and 29 parameters. The differential equations involve Michaelis-Menten kinetics that describe enzyme-mediated protein degradation, and Hill functions that describe some transcriptional activation terms. The model is given by:

$$\begin{align*} \dot{x}_1 &= n_1 \dfrac{x_6}{g_1+x_6} - m_1 \dfrac{x_1}{k_1 + x_1} + q_1x_7u(t),\\ \dot{x}_2 &= p_1x_1 - r_1x_2 + r_2x_3 - m_2 \dfrac{x_2}{k_2 + x_2},\\ \dot{x}_3 &= r_1x_2 - r_2x_3 - m_3 \dfrac{x_3}{k_3 + x_3},\\ \dot{x}_4 &= n_2\dfrac{g_2^2}{x_2^2+x_3^2} - m_4 \dfrac{x_4}{k_4 + x_4},\\ \dot{x}_5 &= p_2x_4 - r_3x_5 + r_4x_6 - m_5 \dfrac{x_5}{k_5 + x_5},\\ \dot{x}_6 &= r_3x_5 - r_4x_6 - m_6 \dfrac{x_6}{k_6 + x_6},\\ \dot{x}_7 &= p_3 - m_7 \dfrac{x_7}{k_7 + x_7} - (p_3 + q_2x_7)u(t) \end{align*}$$

with $x_i(0)=0, i=1,...,7$.

Type: 

Form: 

Model order: 

7

Time domain: 

Linearity: 

Publication details: 

TitleStructural Identifiability of Systems Biology Models: A Critical Comparison of Methods
Publication TypeJournal Article
Year of Publication2011
AuthorsChis, Oana-Teodora, Banga Julio R., and Balsa-Canto Eva
Secondary AuthorsJaeger, JohannesEditor
JournalPLoS ONE
Volume6
Start Page1
Issue11
Pagination1-16
Date Published10/2011
ISSN1932-6203
AbstractAnalysing the properties of a biological system through in silico experimentation requires a satisfactory mathematical representation of the system including accurate values of the model parameters. Fortunately, modern experimental techniques allow obtaining time-series data of appropriate quality which may then be used to estimate unknown parameters. However, in many cases, a subset of those parameters may not be uniquely estimated, independently of the experimental data available or the numerical techniques used for estimation. This lack of identifiability is related to the structure of the model, i.e. the system dynamics plus the observation function. Despite the interest in knowing a priori whether there is any chance of uniquely estimating all model unknown parameters, the structural identifiability analysis for general non-linear dynamic models is still an open question. There is no method amenable to every model, thus at some point we have to face the selection of one of the possibilities. This work presents a critical comparison of the currently available techniques. To this end, we perform the structural identifiability analysis of a collection of biological models. The results reveal that the generating series approach, in combination with identifiability tableaus, offers the most advantageous compromise among range of applicability, computational complexity and information provided.
DOI10.1371/journal.pone.0027755

Biochemical Reaction Network

Model description: 

The system, that could describe a biochemical reaction network, is represented by twenty differential equations, twenty two parameters, and all the states are assumed to be measured:

$$\begin{align*} \dot{x}_1&=-\dfrac{v_{max}x_1}{(k_m+x_1)}-p_1x_1 + u(t),\\ \dot{x}_{2}&=p_{1}x_{1}-p_{2}x_{2},\\ \dot{x}_{3}&=p_{2}x_{2}-p_{3}x_{3},\\ \dot{x}_{4}&=p_{3}x_{3}-p_{4}x_{4},\\ \dot{x}_{5}&=p_{4}x_{4}-p_{5}x_{5},\\ \dot{x}_{6}&=p_{5}x_{5}-p_{6}x_{6},\\ \dot{x}_{7}&=p_{6}x_{6}-p_{7}x_{7},\\ \dot{x}_{8}&=p_{7}x_{7}-p_{8}x_{8},\\ \dot{x}_{9}&=p_{8}x_{8}-p_{9}x_{9},\\ \dot{x}_{10}&=p_{9}x_{9}-p_{10}x_{10},\\ \dot{x}_{11}&=p_{10}x_{10}-p_{11}x_{11},\\ \dot{x}_{12}&=p_{11}x_{11}-p_{12}x_{12},\\ \dot{x}_{13}&=p_{12}x_{12}-p_{13}x_{13},\\ \dot{x}_{14}&=p_{13}x_{13}-p_{14}x_{14},\\ \dot{x}_{15}&=p_{14}x_{14}-p_{15}x_{15},\\ \dot{x}_{16}&=p_{15}x_{15}-p_{16}x_{16},\\ \dot{x}_{17}&=p_{16}x_{16}-p_{17}x_{17},\\ \dot{x}_{18}&=p_{17}x_{17}-p_{18}x_{18},\\ \dot{x}_{19}&=p_{18}x_{18}-p_{19}x_{19},\\ \dot{x}_{20}&=p_{19}x_{19}-p_{20}x_{20},\\ \end{align*}$$

where $x_i, i = 1, …, 20$ are the states. The unknown parameters are $p_i, i = 1, …, 20$, plus the two Michaelis-Menten parameters $ν_{max}$ and $k_m$. All the states are assumed to be measured.

Type: 

Form: 

Model order: 

20

Time domain: 

Linearity: 

Publication details: 

TitleStructural Identifiability of Systems Biology Models: A Critical Comparison of Methods
Publication TypeJournal Article
Year of Publication2011
AuthorsChis, Oana-Teodora, Banga Julio R., and Balsa-Canto Eva
Secondary AuthorsJaeger, JohannesEditor
JournalPLoS ONE
Volume6
Start Page1
Issue11
Pagination1-16
Date Published10/2011
ISSN1932-6203
AbstractAnalysing the properties of a biological system through in silico experimentation requires a satisfactory mathematical representation of the system including accurate values of the model parameters. Fortunately, modern experimental techniques allow obtaining time-series data of appropriate quality which may then be used to estimate unknown parameters. However, in many cases, a subset of those parameters may not be uniquely estimated, independently of the experimental data available or the numerical techniques used for estimation. This lack of identifiability is related to the structure of the model, i.e. the system dynamics plus the observation function. Despite the interest in knowing a priori whether there is any chance of uniquely estimating all model unknown parameters, the structural identifiability analysis for general non-linear dynamic models is still an open question. There is no method amenable to every model, thus at some point we have to face the selection of one of the possibilities. This work presents a critical comparison of the currently available techniques. To this end, we perform the structural identifiability analysis of a collection of biological models. The results reveal that the generating series approach, in combination with identifiability tableaus, offers the most advantageous compromise among range of applicability, computational complexity and information provided.
DOI10.1371/journal.pone.0027755

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