The Systems Biology Markup Language (SBML) is a machine-readable language, based on
XML, for representing models of biochemical reaction networks. SBML can represent metabolic networks, cell-signaling pathways, regulatory networks, and other kinds of systems studied in systems biology.
In the year
2000, with funding from the [http://www.jst.go.jp/EN/ Japan Science and Technology Corporation (JST)] , Hiroaki Kitanoand John C. Doyleassembled a small team of researchers to work on developingbetter software infrastructure for computational modeling in systems biology. Hamid Bolouri was the leader of thedevelopment team, which consisted of Andrew Finney, Herbert Sauro, andMichael Hucka. Their initial work focused on a system to allow asubset of existing simulation software packages to communicate. This subsetconsisted of DBSolve, [http://ecell.sourceforge.net/ E-Cell] , [http://http.gepasi.org Gepasi] , [http://sbw.kgi.edu/software/jarnac.htm Jarnac] , [http://www.pdn.cam.ac.uk/groups/comp-cell/StochSim.html StochSim] and [http://www.nrcam.uchc.edu/ The Virtual Cell] .The groups developing these tools met on April 28-29, 2000 at the ERATOSoftware Platforms for Molecular Biology workshop, held at the California Institute of Technology.It became clear during the workshopthat a common model representation format was neededto enable exchanging models between software tools. Theworkshop attendees decided the format should be encoded in XML.The Caltech ERATO team developed a proposal for a formatand circulated the draft definition to the meeting attendees in August, 2000.This draft underwent extensive discussion over mailing lists andduring the Second Workshop on Software Platforms for SystemsBiology, held in Tokyo, Japan, in November 2000 as a satellite workshop ofthe [http://www.symbio.jst.go.jp/systemsbiology/icsb/ ICSB 2000] conference. After further revisions anddiscussions, the Caltech team issued a specification for [http://www.sbml.org/specifications/sbml-level-1/version-1/ SBML Level 1, Version 1] in March 2001.
SBML Level 2 was conceived at the 5th Workshop on Software Platforms forSystems Biology, held in July 2002, at the
University of Hertfordshire, UK.By this time, far more people were involved than the original group of SBMLcollaborators and the continued evolution of SBML became a larger communityeffort, with many new tools having been enhanced to support SBML.The workshop participants in 2002 collectively decided to revisethe form of SBML in Level 2. The first draft of the [http://www.sbml.org/specifications/sbml-level-2/version-1 Level 2 Version 1] specification was released in August 2002, and the final setof features was finalized in May 2003 at the 7th Workshop on SoftwarePlatforms for Systems Biology in Ft. Lauderdale, Florida.
The next iteration of SBML took two years in part because softwaredevelopers requested time to absorb and understand the larger and morecomplex SBML Level 2. The inevitable discovery of limitations anderrors lead to the development of [http://www.sbml.org/specifications/sbml-level-2/version-2 SBML Level 2 Version 2] , issued in September 2006. By this time, theteam of SBML Editors (who reconcile proposals for changes and write acoherent final specification document) had changed and now consisted ofAndrew Finney, Michael Hucka and Nicolas Le Novère.
[http://www.sbml.org/specifications/sbml-level-2/version-3 SBML Level 2 Version 3] was published in 2007after countless contributions by and discussions with the SBML community. 2007 also saw the election of two more SBML Editors (Sarah Keating and Stefan Hoops). In 2008, Darren Wilkinson and Sven Sahle were elected editors while Andrew Finney and Michael Hucka stepped down. Michael Hucka became chair of the editorial board, as head of the SBML team and PI of the grant supporting SBML development.
SBML has three main purposes:
* enabling the use of multiple software tools without rewriting models for each tool;
* enabling models to be shared and published in a form other researchers can use even in a different software environment;
* ensuring the survival of models beyond the lifetime of the software used to create them.
SBML is not an attempt to define a universal language for quantitative models. SBML's purpose is to serve as a "
lingua franca"—an exchange format used by different present-day software tools to communicate the essential aspects of a computational model.
SBML can encode models consisting of biochemical entities(species) linked by reactions to form biochemical networks.An important principle is that models are decomposed intoexplicitly-labeled constituent elements, the set of whichresembles a verbose rendition of chemical reactionequations; the representation deliberately does not cast themodel directly into a set of differential equations or otherspecific interpretation of the model. This explicit,modeling-framework-agnostic decomposition makes it easierfor a software tool to interpret the model and translate theSBML form into whatever internal form the tool actuallyuses.
A software package can read an SBML model description andtranslate it into its own internal format for modelanalysis. For example, a package might provide the abilityto simulate the model by constructing differential equationsrepresenting the network and then perform numerical timeintegration on the equations to explore the model's dynamicbehavior. Or, alternatively, a package might construct a discrete
stochasticrepresentation of the model and use a Monte Carlo simulation method such as the Gillespie algorithm.
SBML allows models of arbitrary complexity to berepresented. Each type of component in a model is describedusing a specific type of data structure that organizes therelevant information. The data structures determine how theresulting model is encoded in XML.
Levels and versions
SBML is defined in levels: upward-compatible specifications that add features and expressive power.Software toolsthat do not need or cannot support the complexity of higher levels can go on using lowerlevels; tools that can read higher levels are assured of also being able tointerpret models defined in the lower levels. Thus new levels do not supersede old levels. However, each level can have multiple versions; new versions of a level supersede old versions of that same level.
There are now (October 2007) two levels. Current versions are:
* [http://sbml.org/specifications/sbml-level-1/version-2/html/sbml-level-1.html Level 1 Version 2] (SBML L1V2)
* [http://sbml.org/specifications/sbml-level-2/version-3/release-2/sbml-level-2-version-3-rel-2.pdf Level 2 Version 3 Release 2] (SBML L2V3)
Open-source software infrastructure such as [http://sbml.org/software/libsbml libSBML] allows developers tosupport both Levels 1 and 2 in their software with a minimumamount of effort.
SBML Level 2 Version 3 Release 2 is the latest definition of SBML andwas released September 26, 2007.
A model definition inLevel 2 Version 3 consists of lists of one or more of the followingcomponents:
* Function definition: A named mathematical function that may be used throughout the rest of a model.
* Unit definition: A named definition of a new unit of measure, or a redefinition of an existing SBML default unit. Named units can be used in the expression of quantities in a model.
* Compartment Type: A type of location where reacting entities such as chemical substances may be located.
* Species type: A type of entity that can participate in reactions. Examples of species types include ions such as Ca², molecules such as glucose or ATP, binding sites on a protein, and more.
* Compartment: A well-stirred container of a particular type and finite size where species may be located. A model may contain multiple compartments of the same compartment type. Every species in a model must be located in a compartment.
* Species: A pool of entities of the same species type located in a specific compartment.
* Parameter: A quantity with a symbolic name. In SBML, the term parameter is used in a generic sense to refer to named quantities regardless of whether they are constants or variables in a model. SBML Level 2 Version 2 provides the ability to define parameters that are global to a model as well as parameters that are local to a single reaction.
* Initial Assignment: A mathematical expression used to determine the initial conditions of a model. This type of structure can only be used to define how the value of a variable can be calculated from other values and variables at the start of simulated time.
* Rule: A mathematical expression used in combination with the differential equations constructed based on the set of reactions in a model. It can be used to define how a variable's value can be calculated from other variables, or used to define the rate of change of a variable. The set of rules in a model can be used with the reaction rate equations to determine the behavior of the model with respect to time. The set of rules constrains the model for the entire duration of simulated time.
* Constraint: A mathematical expression that defines a constraint on the values of model variables. The constraint applies at all instants of simulated time. The set of constraints in model should not be used to determine the behavior of the model with respect to time.
* Reaction: A statement describing some transformation, transport or binding process that can change the amount of one or more species. For example, a reaction may describe how certain entities (reactants) are transformed into certain other entities (products). Reactions have associated kinetic rate expressions describing how quickly they take place.
* Event: A statement describing an instantaneous, discontinuous change in a set of variables of any type (species concentration, compartment size or parameter value) when a triggering condition is satisfied.
As of December, 2007, more than 120 software systems advertise support SBML. A current list can be found at [http://sbml.org sbml.org] .
SBML has been and continues to be developed by the community of people making software platforms for systems biology, through active email discussion lists and biannual [http://sbml.org/workshops/ workshops] , often held in conjunction with other biology conferences, especially the International Conference on Systems Biology. The community effort is coordinated by an elected editorial board made up of five members. Each editor is elected for a 3-year non-renewable term.
Tools such as an [http://sbml.org/validator/ on-line model validator] and
open-sourcelibraries for incorporating SBML into C, C++, Mathematica, and MATLABare developed partly by the SBML Team and partly by the broader SBML community.
SBML is an official
IETF MIMEtype ("RFC 3823 MIME Media Type for the Systems Biology Markup Language (SBML)")
* Hucka M, Finney A, Sauro HM, Bolouri H, Doyle JC, Kitano H, Arkin AP, Bornstein BJ, Bray D, Cornish-Bowden A, Cuellar AA, Dronov S, Gilles ED, Ginkel M, Gor V, Goryanin II, Hedley WJ, Hodgman TC, Hofmeyr JH, Hunter PJ, Juty NS, Kasberger JL, Kremling A, Kummer U, Le Novere N, Loew LM, Lucio D, Mendes P, Minch E, Mjolsness ED, Nakayama Y, Nelson MR, Nielsen PF, Sakurada T, Schaff JC, Shapiro BE, Shimizu TS, Spence HD, Stelling J, Takahashi K, Tomita M, Wagner J, Wang J. "The systems biology markup language (SBML): a medium for representation and exchange of biochemical network models." "Bioinformatics." 2003 19: 524-531.
* Finney A, Hucka M. "Systems biology markup language: Level 2 and beyond." "Biochem Soc. Trans." 2003 31: 1472-1473.
* Hucka M, Finney A, Bornstein BJ, Keating SM, Shapiro BE, Matthews J, Kovitz BL, Schilstra MJ, Funahashi A, Doyle JC, and Kitano H, “Evolving a Lingua Franca and Associated Software Infrastructure for Computational Systems Biology: The Systems Biology Markup Language (SBML) Project”, "Systems Biology" 1:41-53 (2004).
* Finney A, Hucka M, Bornstein BJ, Keating SM, Shapiro BE, Matthews J, Kovitz BL, Schilstra MJ, Funahashi A, Doyle JC, Kitano H, Software Infrastructure for Effective Communication and Reuse of Computational Models. In "System Modeling in Cellular Biology: From Concepts to Nuts and Bolts," ed. Szallasi Z, Stelling J, Periwal V, MIT Press, 2006.
* http://sbml.org Home site of SBML
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