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BIOMD0000000226 - Radulescu2008_NFkB_hierarchy_M_14_25_28_Lipniacky

 

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Reference Publication
Publication ID: 18854041
Radulescu O, Gorban AN, Zinovyev A, Lilienbaum A.
Robust simplifications of multiscale biochemical networks.
BMC Syst Biol 2008; 2: 86
IRMAR (CNRS UMR 6025), UniversitĂ© de Rennes 1, Rennes, France. ovidiu.radulescu@univ-rennes1.fr  [more]
Model
Original Model: BIOMD0000000226.origin
Submitter: Andrei Zinovyev
Submission ID: MODEL7743386835
Submission Date: 27 Feb 2009 16:28:12 UTC
Last Modification Date: 03 Jun 2014 13:55:54 UTC
Creation Date: 27 Feb 2009 16:28:12 UTC
Encoders:  Vijayalakshmi Chelliah
   Ovidiu Radulescu
set #1
bqmodel:isDerivedFrom BioModels Database Hoffmann2002_WT_IkBNFkB_Signaling
BioModels Database Hoffmann2002_KnockOut_IkBNFkB_Signaling
PubMed 15094015
set #2
bqbiol:isVersionOf Gene Ontology I-kappaB kinase/NF-kappaB signaling
set #3
bqbiol:isPartOf KEGG Pathway T cell receptor signaling pathway - Mus musculus (mouse)
set #4
bqbiol:hasTaxon Taxonomy Mus musculus
Notes

NFkB model M(14,25,28) - Lipniacky's NFkB model

This is a model of NFkB pathway functioning from hierarchy of models of decreasing complexity, created to demonstrate application of model reduction methods proposed in

This a model from the article:
Robust simplifications of multiscale biochemical networks.
Radulescu O, Gorban A., Zinovyev A., Lilienbaum. A. BMC Syst Biol2008:2:86 18854041,
Abstract:
BACKGROUND: Cellular processes such as metabolism, decision making in development and differentiation, signalling, etc., can be modeled as large networks of biochemical reactions. In order to understand the functioning of these systems, there is a strong need for general model reduction techniques allowing to simplify models without loosing their main properties. In systems biology we also need to compare models or to couple them as parts of larger models. In these situations reduction to a common level of complexity is needed. RESULTS: We propose a systematic treatment of model reduction of multiscale biochemical networks. First, we consider linear kinetic models, which appear as "pseudo-monomolecular" subsystems of multiscale nonlinear reaction networks. For such linear models, we propose a reduction algorithm which is based on a generalized theory of the limiting step that we have developed in 1. Second, for non-linear systems we develop an algorithm based on dominant solutions of quasi-stationarity equations. For oscillating systems, quasi-stationarity and averaging are combined to eliminate time scales much faster and much slower than the period of the oscillations. In all cases, we obtain robust simplifications and also identify the critical parameters of the model. The methods are demonstrated for simple examples and for a more complex model of NF-kappaB pathway. CONCLUSION: Our approach allows critical parameter identification and produces hierarchies of models. Hierarchical modeling is important in "middle-out" approaches when there is need to zoom in and out several levels of complexity. Critical parameter identification is an important issue in systems biology with potential applications to biological control and therapeutics. Our approach also deals naturally with the presence of multiple time scales, which is a general property of systems biology models.

This model is originally proposed by Lipniacki 2004 (Lipniacki T, Paszek P, Brasier AR, Luxon B, Kimmel M.(2004). Mathematical model of NF-kappaB regulatory module. J. Theor. Biol. 228 (2): 195-215. 15094015

The models are provided in CellDesigner v3.5 format. The name of the model M(x,y,z) should be deciphered as following:

x - number of species y - number of reactions z - number of parameters

Simulation protocol: The model can be simulated in CellDesigner directly, or in any simulator supporting events. The simulation period should be set up in 20 hours (t=72000 sec). This model reproduces Figure 3b (M(14,25,28)) of the publication.

For additional information please contact Andrei.Zinovyev at curie.fr

This model originates from BioModels Database: A Database of Annotated Published Models. It is copyright (c) 2005-2009 The BioModels Team.
For more information see the terms of use.
To cite BioModels Database, please use Le Novère N., Bornstein B., Broicher A., Courtot M., Donizelli M., Dharuri H., Li L., Sauro H., Schilstra M., Shapiro B., Snoep J.L., Hucka M. (2006) BioModels Database: A Free, Centralized Database of Curated, Published, Quantitative Kinetic Models of Biochemical and Cellular Systems Nucleic Acids Res., 34: D689-D691.

Model
Publication ID: 18854041 Submission Date: 27 Feb 2009 16:28:12 UTC Last Modification Date: 03 Jun 2014 13:55:54 UTC Creation Date: 27 Feb 2009 16:28:12 UTC
Mathematical expressions
Reactions
re44 re45 re46 re47
re48 re49 re52 re53
re56 re57 re58 re59
re60 re61 re63 re64
re65 re66 re67 re68
re69 re70 re71 re72
Physical entities
Compartments Species
default sa13_degraded sa12_degraded mRNAIKBA
mRNAA20 A20 sa444_degraded
IKKi sa19_degraded IKKa
IKKn sa20_degraded NFkB:IkB_alpha
IKKa/IKBa NFkB/Ikb_alpha/IKKa sa96_degraded
sa97_degraded IkB_alpha NFkB
     
nucleus IKBA A20 IKK
NFkB/IkB_alpha NFkB IkB_alpha
Global parameters
k1 k2 k3 k4
k5 k6 k7 k8
k9 k10 k11 k12
kf13 kr13 kf14 kr14
kf15 kr15 k16 k17
k18 k20 k19 k21
k22 kf23 kr23 k27
kf28 kr28 k26  
Reactions (24)
 
 re44 [IKBA] → [mRNAIKBA];   {NFkB}
 
 re45 [mRNAIKBA] → [sa12_degraded];  
 
 re46 [IkB_alpha] → [sa13_degraded];  
 
 re47 [mRNAIKBA] → [IkB_alpha] + [mRNAIKBA];  
 
 re48 [A20] → [mRNAA20];   {NFkB}
 
 re49 [IKKn] → [IKKa];  
 
 re52 [NFkB:IkB_alpha] → [NFkB];   {IKKa}
 
 re53 [IKKn] → [sa19_degraded];  
 
 re56 [IKKa] → [sa20_degraded];  
 
 re57 [IKKa/IKBa] → [IKKa];  
 
 re58 [IKKa] + [NFkB:IkB_alpha] → [NFkB/Ikb_alpha/IKKa];  
 
 re59 [NFkB/Ikb_alpha/IKKa] → [NFkB] + [IKKa];  
 
 re60 [IKKi] → [sa444_degraded];  
 
 re61 [mRNAA20] → [A20] + [mRNAA20];  
 
 re63 [IKKa] → [IKKi];   {A20}
 
 re64 [IKK] → [IKKn];  
 
 re65 [IkB_alpha] + [NFkB] → [NFkB:IkB_alpha];  
 
 re66 [IkB_alpha] + [IKKa] → [IKKa/IKBa];  
 
 re67 [NFkB] → 5.0 × [NFkB];  
 
 re68 5.0 × [NFkB/IkB_alpha] → [NFkB:IkB_alpha];  
 
 re69 [NFkB] + [IkB_alpha] → [NFkB/IkB_alpha];  
 
 re70 [mRNAA20] → [sa96_degraded];  
 
 re71 [A20] → [sa97_degraded];  
 
 re72 [IkB_alpha] → 5.0 × [IkB_alpha];  
 
  Spatial dimensions: 3.0  Compartment size: 1.0
 
 sa13_degraded
Compartment: default
Initial amount: 0.0
Constant
 
 sa12_degraded
Compartment: default
Initial amount: 0.0
Constant
 
 mRNAIKBA
Compartment: default
Initial amount: 0.0
 
 mRNAA20
Compartment: default
Initial amount: 0.0
 
 A20
Compartment: default
Initial amount: 0.0
 
 sa444_degraded
Compartment: default
Initial amount: 0.0
Constant
 
 IKKi
Compartment: default
Initial amount: 0.0
 
 sa19_degraded
Compartment: default
Initial amount: 0.0
Constant
 
 IKKa
Compartment: default
Initial amount: 0.0
 
 IKKn
Compartment: default
Initial amount: 0.0
 
 sa20_degraded
Compartment: default
Initial amount: 0.0
Constant
 
 NFkB:IkB_alpha
Compartment: default
Initial amount: 0.06
 
 IKKa/IKBa
Compartment: default
Initial amount: 0.0
 
 NFkB/Ikb_alpha/IKKa
Compartment: default
Initial amount: 0.0
 
 sa96_degraded
Compartment: default
Initial amount: 0.0
Constant
 
 sa97_degraded
Compartment: default
Initial amount: 0.0
Constant
 
 IkB_alpha
Compartment: default
Initial amount: 0.0
 
 NFkB
Compartment: default
Initial amount: 0.0
 
 nucleus Spatial dimensions: 3.0  Compartment size: 1.0
 
 IKBA
Compartment: nucleus
Initial amount: 0.0
Constant
 
 A20
Compartment: nucleus
Initial amount: 0.0
Constant
 
 IKK
Compartment: nucleus
Initial amount: 0.0
Constant
 
 NFkB/IkB_alpha
Compartment: nucleus
Initial amount: 0.0
 
 NFkB
Compartment: nucleus
Initial amount: 0.0
 
 IkB_alpha
Compartment: nucleus
Initial amount: 0.0
 
Global Parameters (31)
 
   k1
Value: 0.0025
Constant
 
   k2
Value: 1.25E-4
Constant
 
   k3
Value: 2.5E-6
 
   k4
Value: 0.1
Constant
 
   k5
Value: 0.0015
Constant
 
   k6
Value: 1.25E-4
Constant
 
   k7
Value: 0.2
Constant
 
   k8
Value: 0.1
Constant
 
   k9
Value: 1.0
Constant
 
   k10
Value: 0.1
Constant
 
   k11
Value: 1.25E-4
Constant
 
   k12
Value: 2.0E-5
Constant
 
   kf13
Value: 18.4
Constant
 
   kr13
Constant
 
   kf14
Value: 18.4
Constant
 
   kr14
Constant
 
   kf15
Value: 0.0025
Constant
 
   kr15
Constant
 
   k16
Value: 0.5
Constant
 
   k17
Value: 4.0E-4
Constant
 
   k18
Value: 3.0E-4
Constant
 
   k20
Value: 5.0E-7
Constant
 
   k19
Constant
 
   k21
Value: 1.0E-4
Constant
 
   k22
Value: 0.5
Constant
 
   kf23
Value: 0.0010
Constant
 
   kr23
Value: 5.0E-4
Constant
 
   k27
Value: 4.0E-4
Constant
 
   kf28
Value: 0.01
Constant
 
   kr28
Constant
 
   k26
Value: 5.0E-7
Constant
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000226

Curator's comment: (updated: 07 Aug 2009 11:15:27 BST)

Figure 3b (M(14,25_28)) of the reference publication is reproduced. The model was integrated and simulated using Mathematica 6.0 - MathSBML 2.7.1

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