On Sep 3, 6:35pm, Petr Kuzmic wrote:
> Subject: Re: MCA & numerical analysis
>> I looked, but before I take the trip to the library to read ...
>> Garfinkel D, Kohn MC, Achs MJ, Phifer J, and Roman G-C. Construction of
> more reliable complex metabolic models without repeated solution of
> their constituent differential equations, Math Computers Simulation
> 1978; 20:18.
>> ...do you think the construction of complex metabolic models _without
> solving differential equations_ could be summarized in a few words?
> What assumptions had to be made? Is there a full text of this paper
> posted somewhere?
>> ------------------------+------------------------
> Petr Kuzmic, Ph.D. | (608) 256-4790
> BioKin Consulting | fax (708) 256-1269
> P.O. Box 8336 | pkuzmic at biokin.com> Madison WI 53708 | http://www.biokin.com> ------------------------+------------------------
>-- End of excerpt from Petr Kuzmic
This little paper describes the *construction* of the model, i.e. the
identification of its structure and the values of its parameters, not the
solution of the differential equations, i.e. simulation of a particular
experiment. This task is performed by the engineering technique of
decomposition whereby the system is broken into pieces which minimally
communicate with each other. The model structure and parameter values are found
such that they produce a fit to the data for a series of instantaneous states.
This is determined by verifying that the deduced values for the variables in
the equations--i.e. intermediate concentrations--when substituted into the
enzymatic rate laws for the isolated submodel reproduce the observed
instantaneous fluxes. Finally, all the submodels are reassembled into the
global model. If you've done your work correctly, the solution of the entire
model by integration of its simultaneous differential equations will also
reproduce the instantaneous states at the time points chosen for analysis in
the decomposition.
Petr, I no longer have any copies of the paper you cited, but I have mailed you
D Garfinkel, MC Kohn, MJ Achs, & L Garfinkel, Construction of
metabolic models using artificial intelligence techniques. In:
Artificial Intelligence in Scientific Computation, R Huber et al.,
eds., JC Baltzer AG:Basel, 1989, p 225-231.
which is a more formal explanation of the technique.
--
Michael C. Kohn
Laboratory of Computational Biology and Risk Analysis
National Institute of Environmental Health Sciences
P.O. Box 12233, Mail Drop A3-06
Research Triangle Park, NC 27709-2233
Telephone:
919-541-4929 (voice)
919-541-1479 (fax)
e-mail:
kohn at valiant.niehs.nih.gov
WWW home page:
http://valiant.niehs.nih.gov
