Dataset Information

Jenkinson2011_EGF_MAPK

ABSTRACT: This is a model described in the article: Thermodynamically Consistent Model Calibration in Chemical Kinetics. Garrett Jenkinson and John Goutsias, BMC Systems Biology 2011 May 6;5(1):64.; PMID:21548948. ABSTRACT: BACKGROUND: The dynamics of biochemical reaction systems are constrained by the fundamental laws of thermodynamics, which impose well-defined relationships among the reaction rate constants characterizing these systems. Constructing biochemical reaction systems from experimental observations often leads to parameter values that do not satisfy the necessary thermodynamic constraints. This can result in models that are not physically realizable and may lead to inaccurate, or even erroneous, descriptions of cellular function. RESULTS: We introduce a thermodynamically consistent model calibration (TCMC) method that can be effectively used to provide thermodynamically feasible values for the parameters of an open biochemical reaction system. The proposed method formulates the model calibration problem as a constrained optimization problem that takes thermodynamic constraints (and, if desired, additional non-thermodynamic constraints) into account. By calculating thermodynamically feasible values for the kinetic parameters of a well-known model of the EGF/ERK signaling cascade, we demonstrate the qualitative and quantitative significance of imposing thermodynamic constraints on these parameters and the effectiveness of our method for accomplishing this important task. MATLAB software, using the Systems Biology Toolbox 2.1, can be accessed from www.cis.jhu.edu/~goutsias/CSS lab/software.html. An SBML file containing the thermodynamically feasible EGF/ERK signaling cascade model can be found in the BioModels database. CONCLUSIONS: TCMC is a simple and flexible method for obtaining physically plausible values for the kinetic parameters of open biochemical reaction systems. It can be effectively used to recalculate a thermodynamically consistent set of parameter values for existing thermodynamically infeasible biochemical reaction models of cellular function as well as to estimate thermodynamically feasible values for the parameters of new models. Furthermore, TCMC can provide dimensionality reduction, better estimation performance, and lower computational complexity, and can help to alleviate the problem of data overfitting. This model is a thermodynamically feasible version of a previous model in the BioModels database,BIOMD0000000019, described in Computational modeling of the dynamics of the MAP kinase cascade activated by surface and internalized EGF receptors. Schoeberl et al (2002), PMID:11923843. The only difference between the present model and the model listed under BIOMD0000000019 are the values of the parameters. This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2012 The BioModels.net Team. For more information see the terms of use. To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

SUBMITTER: Garrett Jenkinson

PROVIDER: BIOMD0000000399 | BioModels | 2011-11-03

REPOSITORIES: BioModels

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Publications

Thermodynamically consistent model calibration in chemical kinetics.

Jenkinson Garrett G Goutsias John J

BMC systems biology 20110506

<h4>Background</h4>The dynamics of biochemical reaction systems are constrained by the fundamental laws of thermodynamics, which impose well-defined relationships among the reaction rate constants characterizing these systems. Constructing biochemical reaction systems from experimental observations often leads to parameter values that do not satisfy the necessary thermodynamic constraints. This can result in models that are not physically realizable and may lead to inaccurate, or even erroneous, ...[more]

PMID: 21548948

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Project description:The experiment was designed to enable validation of pre-processing and test algorithms. The in-house produced cDNA-array contains 44 clones: 19 clones from mice, 4 clones from Pine (involved in photosynthesis) and 21 artificial clones from the Lucidea Universal ScoreCard (Amersham Bioscienses), where each clone was printed 480 times in 48 identically designed sub-grids. The experiment contains eight arrays with identical experimental design. Total RNA from murine cell line was divided in two samples; the reference sample was labeled with the fluorophore Cy5 and spiked with the Lucidea Universal ScoreCard reference reaction, the test sample was labeled with Cy3 and spiked with the Lucidea Universal ScoreCard test reaction. The concentrations of the Lucidea reactions are known and consequently so are the true ratios between the reference and test channels. Approximately 40% of the artificial genes were differentially expressed. The particular design of the experiment makes the data suitable for validating algorithms for pre-processing and tests for identifying differentially expressed genes. - The 80.I.1 normalization algorithm : all spots flagged as not found during image analysis considered missing values (complete filtration). Print-tip MA-loess dye normalization based on the calibration clones was applied to the raw data and the B-statistic was calculated. - The 80.II.1 normalization algorithm : all spots flagged as not found during image analysis considered missing values (complete filtration). Local background correction was applied and all spots with negative values were excluded. Print-tip MA-loess dye normalization based on the calibration clones was applied to the background corrected data and the B-statistic was calculated. - The 80.II.64 normalization algorithm : all spots flagged as not found during image analysis considered missing values (complete filtration). Local background correction was applied, negative values were excluded and all spots with a value below 64 were set to 64 (censored). Print-tip MA-loess dye normalization based on the calibration clones was applied to the background corrected data and the B-statistic was calculated. - The 80.V.1 normalization algorithm : The intensities of all spots flagged not found were treated as missing values during normalization, but prior to calculating test-statistics the spot's log-ratios were set to zero. In the special case when all arrays generated not-found spots, the gene was removed from the experiment (Partial filtration). Local background correction was applied and all negative values were considered missing values. Print-tip MA-loess dye normalization based on the calibration clones was applied to the background corrected data and the B-statistic was calculated. The experiment contains eight arrays with identical experimental design. The reference sample was labeled with the fluorophore Cy5 and spiked with the Lucidea Universal ScoreCard reference reaction, the test sample was labeled with Cy3 and spiked with the Lucidea Universal ScoreCard test reaction.

Dataset Information

Jenkinson2011_EGF_MAPK

Publications

Thermodynamically consistent model calibration in chemical kinetics.

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