Automated construction and analysis of the design space for biochemical systems.
BACKGROUND
Our recent work introduced a generic method to construct the design space of biochemical systems: a representation of the relationships between system parameters, environmental variables and phenotypic behavior. In design space, the qualitatively distinct phenotypes of a biochemical system can be identified, counted, analyzed and compared. Boundaries in design space indicate a transition between phenotypic behaviors and can be used to measure a system's tolerance to large changes in parameters. Moreover, the relative size and arrangement of such phenotypic regions can suggest or confirm global properties of the system.


RESULTS
Our work here demonstrates that the construction and analysis of design space can be automated. We present a formal description of design space and a detailed explanation of its construction. We also extend the notion to include variable kinetic orders. We describe algorithms that automate common steps of design space construction and analysis, introduce new analyses that are made possible by such automation and discuss challenges of implementation and scaling. In the end, we demonstrate the techniques using software we have created.


BACKGROUND
The Design Space Toolbox for MATLAB is freely available at http://www.bme.ucdavis.edu/savageaulab/


BACKGROUND
masavageau@ucdavis.edu
Fasani
Rick A
RA
Department of Biomedical Engineering, University of California, Davis, CA 95616, USA.
Savageau
Michael A
MA
D001331:Automation; D001669:Biochemical Phenomena; D019295:Computational Biology / Q000379:methods*; D008954:Models, Biological; D010641:Phenotype; D049490:Systems Biology / Q000379:methods
Arch Biochem Biophys. 1971 Aug;145(2):612-21
4332048
Nat Biotechnol. 2008 Oct;26(10):1135-45
18846087
Nature. 1971 Feb 19;229(5286):542-4
4925348
PLoS Comput Biol. 2009 Mar;5(3):e1000319
19300483
FEBS Lett. 2009 Dec 17;583(24):3914-22
19879266
Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7
271968
Nature. 1974 Dec 13;252(5484):546-9
4431516
Cell. 2003 May 30;113(5):597-607
12787501
J Mol Biol. 1996 Jan 12;255(1):121-39
8568860
Chaos. 2001 Mar;11(1):142-159
12779449
Nat Rev Genet. 2010 Jan;11(1):31-46
19997069
J Mol Evol. 1975 Aug 5;5(3):199-222
1159800
Science. 2001 Feb 16;291(5507):1304-51
11181995
Nature. 2001 Feb 15;409(6822):860-921
11237011
J Mol Biol. 1995 May 12;248(4):739-55
7752237
Math Biosci. 2002 Nov-Dec;180:237-53
12387925
Proc Natl Acad Sci U S A. 2009 Apr 21;106(16):6435-40
19279208