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Title: How to deal with large models?

Journal Article · · Molecular Systems Biology
 [1]
  1. Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Division and Center for Nonlinear Studies. Theoretical Biology and Biophysics Group; DOE/OSTI

The regulatory systems that allow cells to adapt to their environments are exceedingly complex, and although we know a great deal about the intricate mechanistic details of many of these systems, our ability to make accurate predictions about their system-level behaviors is severely limited. We would like to make such predictions for a number of reasons. How can we reverse dysfunctional molecular changes of these systems that cause disease? More generally, how can we harness and direct cellular activities for beneficial purposes? Our ability to make accurate predictions about a system is also a measure of our fundamental understanding of that system. As evidenced by our mastery of technological systems, a useful understanding of a complex system can often be obtained through the development and analysis of a mathematical model, but predictive modeling of cellular regulatory systems, which necessarily relies on quantitative experimentation, is still in its infancy. There is much that we need to learn before modeling for practical applications becomes routine. In particular, we need to address a number of issues surrounding the large number of parameters that are typically found in a model for a cellular regulatory system.

Research Organization:
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
Grant/Contract Number:
AC52-06NA25396
OSTI ID:
1629292
Journal Information:
Molecular Systems Biology, Journal Name: Molecular Systems Biology Journal Issue: 1 Vol. 5; ISSN 1744-4292
Publisher:
WileyCopyright Statement
Country of Publication:
United States
Language:
English

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Input–output behavior of ErbB signaling pathways as revealed by a mass action model trained against dynamic data journal January 2009
Modular cell biology: retroactivity and insulation journal January 2008
Computational modeling of the dynamics of the MAP kinase cascade activated by surface and internalized EGF receptors journal April 2002
Minimum information requested in the annotation of biochemical models (MIRIAM) journal December 2005
Heterogeneity in EGF-binding affinities arises from negative cooperativity in an aggregating system journal December 2007
BIOCHAM: an environment for modeling biological systems and formalizing experimental knowledge journal May 2006
Kinetic Monte Carlo method for rule-based modeling of biochemical networks journal September 2008
Rules for Modeling Signal-Transduction Systems journal July 2006
MIRIAM Resources: tools to generate and resolve robust cross-references in Systems Biology journal December 2007
Universally Sloppy Parameter Sensitivities in Systems Biology Models journal January 2007
A Dual Receptor Crosstalk Model of G-Protein-Coupled Signal Transduction journal September 2008
On Imposing Detailed Balance in Complex Reaction Mechanisms journal August 2006
Thermodynamically Feasible Kinetic Models of Reaction Networks journal March 2007

Cited By (15)

Qualitatively distinct phenotypes in the design space of biochemical systems journal October 2009
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Automated adaptive inference of phenomenological dynamical models journal August 2015
A Multiscale Model of Interleukin-6-Mediated Immune Regulation in Crohn's Disease and Its Application in Drug Discovery and Development journal January 2014
Convergence in parameters and predictions using computational experimental design journal August 2013
Multi-level model for the investigation of oncoantigen-driven vaccination effect journal April 2013
Decoding complex biological networks - tracing essential and modulatory parameters in complex and simplified models of the cell cycle journal January 2011
A Boolean probabilistic model of metabolic adaptation to oxygen in relation to iron homeostasis and oxidative stress journal January 2011
Model composition through model reduction: a combined model of CD95 and NF-κB signaling pathways journal January 2013
Optimization and model reduction in the high dimensional parameter space of a budding yeast cell cycle model journal January 2013
Likelihood based observability analysis and confidence intervals for predictions of dynamic models text January 2011
Automated adaptive inference of coarse-grained dynamical models in systems biology preprint January 2014
Programming biological models in Python using PySB journal January 2013
Automated adaptive inference of phenomenological dynamical models journal August 2015
A Boolean probabilistic model of metabolic adaptation to oxygen in relation to iron homeostasis and oxidative stress journal January 2011

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