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Modeling cardiac β-adrenergic signaling with normalized-Hill differential equations: comparison with a biochemical model
2010
BMC Systems Biology
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Comprehensive sensitivity analysis revealed the significant role of PKA negative feedback on upstream signaling and the importance of phosphodiesterases as key negative regulators of the network. ...
with biochemical models. ...
Jason Papin for critical review of the manuscript. This work was supported by National Institutes of Health grant HL094476 and the American Heart Association grant 0830470N. ...
doi:10.1186/1752-0509-4-157
pmid:21087478
pmcid:PMC2993667
fatcat:kknw4a6myjcrtehgswk4kp247e
Analysis of Synergism in Biochemical Networks
2010
Food Technology and Biotechnology
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It is based on system analysis concept when information on the importance of a parameter of a complex biochemical model is evaluated as part of joint interaction with a complete set of model parameters ...
Probabilistic approach to analysis of synergism in mathematical models of biochemical networks is introduced. ...
(15) for the analysis of kinetic parameter sensitivities in chemical kinetic models. ...
doaj:df7e3088cd8d4f1d86030a6362ebd12e
fatcat:adhzifggpzenzg7d5nt6zxrs74
Dynamic modelling and analysis of biochemical networks: mechanism-based models and model-based experiments
2006
Briefings in Bioinformatics
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Current approaches and methods of parameter sensitivity analysis and parameter estimation are reviewed. ...
Mathematical models of biochemical networks can look very different. ...
Only recently global parameter sensitivity analysis (GPSA) methods have been started to be applied to biochemical network models [42, 45, 46, 59] . ...
doi:10.1093/bib/bbl040
pmid:17107967
fatcat:seoscbai2bblfd37izrnu2jnb4
MODELING AND ANALYSIS OF BIOPATHWAYS DYNAMICS
2012
Journal of Bioinformatics and Computational Biology
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Cellular processes are governed and coordinated by a multitude of biopathways. A pathway can be viewed as a complex network of biochemical reactions. ...
Hence the modeling and analysis of biochemical networks dynamics is an important problem and is an active area of research. ...
Global sensitivity analysis. To perform global sensitivity analysis, Monte Carlo samples are drawn from the discretized parameter space. ...
doi:10.1142/s0219720012310014
pmid:22809413
fatcat:7mpayoxcqvdgjf4l3ti2uh3p24
Robustness portraits of diverse biological networks conserved despite order-of-magnitude parameter uncertainty
2011
Computer applications in the biosciences : CABIOS
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Results: Here, we examined a model of cardiac β-adrenergic signaling and found that its robustness portrait, a global measure of steady-state network function, was well conserved even when all parameters ...
Motivation: Biological networks are robust to a wide variety of internal and external perturbations, yet fragile or sensitive to a small minority of perturbations. ...
(A) Partial sensitivity matrix of original β-adrenergic model, with species ordered upstream to downstream in the pathway. ...
doi:10.1093/bioinformatics/btr496
pmid:21880701
pmcid:PMC3187657
fatcat:yqjhj4fp7zbjdn7byaye6hrvp4
Employing optimization and sensitivity analyses tools to generate and analyze mathematical models of T cell signaling events
2007
AIP Conference Proceedings
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In isolation, the sensitivity analyses driven approach failed to converge to a model interpretable within the context of known signaling pathway information. ...
Approaches using optimization and sensitivity analysis to generate and analyze mathematical models relating to T cell signaling are reviewed and extended. ...
ACKNOWLEDGMENTS This work was supported by NSF Grant CNS-0643805 and a NSF Graduate Research Fellowship. ...
doi:10.1063/1.2817353
fatcat:zs62ugsf4ndyvpvfmobsctqcfq
Systems glycobiology: biochemical reaction networks regulating glycan structure and function
2011
Glycobiology
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of biochemical processes enable the study of biological "systems" as a whole. ...
unknown model parameters, (iv) post-simulation analysis methods that yield experimentally testable hypotheses and (v) a summary of available software tools that can be used by non-specialists to perform ...
Conflict of interest None declared. ...
doi:10.1093/glycob/cwr036
pmid:21436236
pmcid:PMC3219416
fatcat:75crtbe3hndqbavcsljfuaagau
Bioengineering Models of Cell Signaling
2000
Annual Review of Biomedical Engineering
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These may involve a two-level hierarchical approach wherein the overall signaling network is modeled in terms of effective "circuit" or "algorithm" modules, and then each module is correspondingly modeled ...
Three crucial attributes of signal transduction necessitate modeling approaches for analyzing these systems: an ever-expanding plethora of signaling molecules and interactions, a highly interconnected ...
TOWARD INTEGRATED NETWORK MODELS Alongside analysis of both biochemical and biophysical elements governing specific signaling pathways, it will be equally essential to integrate these pathways into a network ...
doi:10.1146/annurev.bioeng.2.1.31
pmid:11701506
fatcat:reyqhfgf2beh5akhia73auqqre
Reconstructing biochemical pathways from time course data
2007
Proteomics
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We present a new method to infer biochemical pathway mechanisms from time course data using a global nonlinear modeling technique to identify the elementary reaction steps which constitute the pathway. ...
The method involves the generation of a complete dictionary of polynomial basis functions based on the law of mass action. ...
This may result in the identification of local minima, instead of attaining a global minimum [39] . We have introduced the use of a sensitivity-based analysis for model verification. ...
doi:10.1002/pmic.200600428
pmid:17370261
fatcat:ogx7htkytrhshbhobcym643ree
Reduced-order modelling of biochemical networks: application to the GTPase-cycle signalling module
2005
IEE Proceedings - Systems Biology
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Coarse-grained biochemical models, called reduced-order models (ROMs), consisting of essential biochemical mechanisms are more useful for computational analysis and for studying important features of a ...
Biochemical systems embed complex networks and hence development and analysis of their detailed models pose a challenge for computation. ...
Acknowledgments This work of Subramaniam was supported by National Institute of Health Grant U54 GM62114. We thank Prof. Elliott M. ...
doi:10.1049/ip-syb:20050014
pmid:16986265
pmcid:PMC3417759
fatcat:55ridnjgvndprddensjhi7fsdy
A General Network Pharmacodynamic Model–Based Design Pipeline for Customized Cancer Therapy Applied to the VEGFR Pathway
2014
CPT: Pharmacometrics & Systems Pharmacology
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protein kinase and Akt cascade activation, was linked to a sunitinib (VEGFR inhibitor) PK model and underwent Sobol sensitivity analysis that revealed potential sunitinib-enhancing mechanisms. ...
This pipeline of computational analyses demonstrates how model-based methods can capture the complexities of drug action, tailor cancer chemotherapy, and empower personalized medicine. ...
Thanks to Jonathan Herman at Penn State University for helpful discussions and software for Sobol sensitivity analysis. ...
doi:10.1038/psp.2013.65
pmid:24429593
pmcid:PMC3910016
fatcat:bb5eefn3dnamhfozoetc6r33tu
Dynamic Modeling of the Human Coagulation Cascade Using Reduced Order Effective Kinetic Models
2015
Processes
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We then used flux analysis to understand how the network operated in a variety of conditions, and global sensitivity analysis to identify which parameters controlled the performance of the network. ...
In this study, we present a novel modeling approach which combines ordinary differential equation (ODE) modeling with logical rules to simulate an archetype biochemical network, the human coagulation cascade ...
Author Contributions A.S. and J.V. conceived of and developed the coagulation model. J.V. supervised the project, and prepared the manuscript. ...
doi:10.3390/pr3010178
fatcat:i6ocolavszgbrjmlqta7leuoxm
Mathematical modeling reveals threshold mechanism in CD95-induced apoptosis
2004
Journal of Cell Biology
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A new approach for sensitivity analysis within the mathematical model was key for the identification of critical system parameters and two essential system properties: modularity and robustness. ...
Our model describes the regulation of apoptosis on a systems level and resolves the important question of a threshold mechanism for the regulation of apoptosis. M. Bentele and I. ...
A global sensitivity analysis is usually impaired by the high dimensionality of the parameter space. ...
doi:10.1083/jcb.200404158
pmid:15364960
pmcid:PMC2172102
fatcat:2n24ohrcmvcwzkhlako7sonzpm
Model-based selection of the robust JAK-STAT activation mechanism
2012
Journal of Theoretical Biology
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Therefore, we comparatively investigate changes in a robustness of the JAK1/2-STAT1 pathway variants using the global sensitivity analysis method (GSA), complemented with the identifiability analysis ( ...
Here, we compare four variants of a computational model of the JAK1/2-STAT1 signaling pathway. ...
The first author is a scholar within the ...
doi:10.1016/j.jtbi.2012.04.031
pmid:22677400
fatcat:zgxnsz5mhzgmnjqvvwvcwqx3wa
Novel global sensitivity analysis methodology accounting for the crucial role of the distribution of input parameters: application to systems biology models
2012
International Journal of Robust and Nonlinear Control
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A model of a biochemical pathway with three enzymatic steps is used here to illustrate the performance of several relevant GSA methods considering different probability density functions for the parameters ...
The reliability of model predictions is affected by multiple sources of uncertainty, therefore most of the efforts for modeling biological systems include a sensitivity analysis step aiming to identify ...
The mathematical formulation of the dynamic model consists Biochemical pathway scheme. ...
doi:10.1002/rnc.2797
fatcat:d5h6k4rfzza27aw53qhiqrtquu
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