Background:
The development of complex biochemical models has been facilitated through
the standardization of machine-readable representations like SBML (Systems
Biology Markup Language). This effort is accompanied by the ongoing
development of the human-readable diagrammatic representation SBGN (Systems
Biology Graphical Notation). The graphical SBML editor CellDesigner allows
direct translation of SBGN into SBML, and vice versa. For the assignment of
kinetic rate laws, however, this process is not straightforward, as it often
requires manual assembly and specific knowledge of kinetic equations.
Results:
SBMLsqueezer facilitates exactly this modeling step via automated equation
generation, overcoming the highly error-prone and cumbersome process of
manually assigning kinetic equations. For each reaction the kinetic equation
is derived from the stoichiometry, the participating species (e.g., proteins,
mRNA or simple molecules) as well as the regulatory relations (activation,
inhibition or other modulations) of the SBGN diagram. Such information
allows distinctions between, for example, translation, phosphorylation
or state transitions. The types of kinetics considered are numerous,
for instance generalized mass-action, Hill, convenience and several
Michaelis-Menten-based kinetics, each including activation and inhibition.
These kinetics allow SBMLsqueezer to cover metabolic, gene regulatory,
signal transduction and mixed networks. Whenever multiple kinetics
are applicable to one reaction, parameter settings allow for user-defined
specifications. After invoking SBMLsqueezer, the kinetic formulas
are generated and assigned to the model, which can then be simulated
in CellDesigner or with external ODE solvers. Furthermore, the equations
can be exported to SBML, LATEX or plain text format.
Conclusion:
SBMLsqueezer considers the annotation of all participating reactants,
products and regulators when generating rate laws for reactions.
Thus, for each reaction, only applicable kinetic formulas are considered.
This modeling scheme creates kinetics in accordance with the diagrammatic
representation. In contrast most previously published tools have
relied on the stoichiometry and generic modulators of a reaction,
thus ignoring and potentially conflicting with the information expressed
through the process diagram. Additional material and the source code
can be found at the project homepage (URL found in the Availability
and requirements section).
@article{Draeger2008,
author = {Dr\"ager, Andreas and Hassis, Nadine and Supper, Jochen and Schr\"oder,
Adrian and Zell, Andreas},
title = {{SBMLsqueezer: a CellDesigner plug-in to generate kinetic rate equations
for biochemical networks}},
journal = {BMC Systems Biology},
year = {2008},
volume = {2},
pages = {39},
number = {1},
month = apr,
abstract = {Background:
The development of complex biochemical models has been facilitated through
the standardization of machine-readable representations like SBML (Systems
Biology Markup Language). This effort is accompanied by the ongoing
development of the human-readable diagrammatic representation SBGN (Systems
Biology Graphical Notation). The graphical SBML editor CellDesigner allows
direct translation of SBGN into SBML, and vice versa. For the assignment of
kinetic rate laws, however, this process is not straightforward, as it often
requires manual assembly and specific knowledge of kinetic equations.
Results:
SBMLsqueezer facilitates exactly this modeling step via automated equation
generation, overcoming the highly error-prone and cumbersome process of
manually assigning kinetic equations. For each reaction the kinetic equation
is derived from the stoichiometry, the participating species (e.g., proteins,
mRNA or simple molecules) as well as the regulatory relations (activation,
inhibition or other modulations) of the SBGN diagram. Such information
allows distinctions between, for example, translation, phosphorylation
or state transitions. The types of kinetics considered are numerous,
for instance generalized mass-action, Hill, convenience and several
Michaelis-Menten-based kinetics, each including activation and inhibition.
These kinetics allow SBMLsqueezer to cover metabolic, gene regulatory,
signal transduction and mixed networks. Whenever multiple kinetics
are applicable to one reaction, parameter settings allow for user-defined
specifications. After invoking SBMLsqueezer, the kinetic formulas
are generated and assigned to the model, which can then be simulated
in CellDesigner or with external ODE solvers. Furthermore, the equations
can be exported to SBML, \LaTeX{} or plain text format.
Conclusion:
SBMLsqueezer considers the annotation of all participating reactants,
products and regulators when generating rate laws for reactions.
Thus, for each reaction, only applicable kinetic formulas are considered.
This modeling scheme creates kinetics in accordance with the diagrammatic
representation. In contrast most previously published tools have
relied on the stoichiometry and generic modulators of a reaction,
thus ignoring and potentially conflicting with the information expressed
through the process diagram. Additional material and the source code
can be found at the project homepage (URL found in the Availability
and requirements section).},
doi = {10.1186/1752-0509-2-39},
pdf = {http://www.biomedcentral.com/content/pdf/1752-0509-2-39.pdf},
url = {http://www.biomedcentral.com/1752-0509/2/39}
}