Paper Info
Title
SBMLsqueezer: a CellDesigner plug-in to generate kinetic rate equations for biochemical networks.
Abstract
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.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.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).
Year
DOI
Venue
2008
10.1186/1752-0509-2-39
BMC systems biology
Keywords
Field
DocType
systems biology,state transition,system biology,gene regulatory networks,signal transduction,rate equation,kinetics,source code,g protein,bioinformatics,algorithms,database management systems
Diagrammatic reasoning,Computer science,Systems biology,Theoretical computer science,Systems Biology Graphical Notation,Plug-in,Bioinformatics,Gene regulatory network,Kinetic equations,SBML,Markup language
Journal
Volume
Issue
ISSN
2
1
1752-0509
Citations 
PageRank 
References 
22
1.67
17
Authors
5
Name
Order
Citations
PageRank
Andreas Dräger129222.16
Nadine Hassis2342.60
Jochen Supper31068.69
Adrian Schröder4383.45
Andreas Zell51419137.58