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Modeling cardiac β-adrenergic signaling with normalized-Hill differential equations: comparison with a biochemical model

Matthew J Kraeutler, Anthony R Soltis, Jeffrey J Saucerman
2010 BMC Systems Biology  
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

Želimir Kurtanjek
2010 Food Technology and Biotechnology  
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

N. A.W. van Riel
2006 Briefings in Bioinformatics  
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


2012 Journal of Bioinformatics and Computational Biology  
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

Anthony R. Soltis, Jeffrey J. Saucerman
2011 Computer applications in the biosciences : CABIOS  
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

Maia M. Donahue, Wei Zhang, Marietta L. Harrison, Jianghai Hu, Ann E. Rundell, Onur Seref, O. Erhun Kundakcioglu, Panos Pardalos
2007 AIP Conference Proceedings  
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

S. Neelamegham, G. Liu
2011 Glycobiology  
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

Anand R. Asthagiri, Douglas A. Lauffenburger
2000 Annual Review of Biomedical Engineering  
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

Jeyaraman Srividhya, Edmund J. Crampin, Patrick E. McSharry, Santiago Schnell
2007 Proteomics  
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

M.R. Maurya, S.J. Bornheimer, V. Venkatasubramanian, S. Subramaniam
2005 IEE Proceedings - Systems Biology  
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

X-Y Zhang, M R Birtwistle, J M Gallo
2014 CPT: Pharmacometrics & Systems Pharmacology  
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

Adithya Sagar, Jeffrey Varner
2015 Processes  
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

M. Bentele, I. Lavrik, M. Ulrich, S. Stößer, D.W. Heermann, H. Kalthoff, P.H. Krammer, R. Eils
2004 Journal of Cell Biology  
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

Mikołaj Rybiński, Anna Gambin
2012 Journal of Theoretical Biology  
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

Maria Rodriguez-Fernandez, Julio R. Banga, Francis J. Doyle
2012 International Journal of Robust and Nonlinear Control  
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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