SBML originated out of a workshop on software platforms for systems biology held in the year 2000 with funding by the Japan Science and Technology Corporation (JST). The original authors were Michael Hucka, Andrew Finney, Herbert Sauro and Hamid Bolouri, but SBML is now very much a community effort. Please see Section 8 for more details about the history of SBML. See Section 7 about how you can participate in SBML's evolution.

We are attempting to have the SBML development process meet the requirements of the community it serves. The editors considered submitting SBML as a proposal to the Object Management Group (OMG) in response to a request for proposals (RFP) for pathways representations.

The Systems Biology Markup Language (SBML) is a machine-readable format for describing qualitative and quantitative models of biochemical networks. It can also be used to express the interactions of biochemical networks with other phenomena. By a ''biochemical network'', we mean a system consisting of biochemical entities linked by chemical reactions that alter, transport and/or transform the entities.

SBML is designed to enable the exchange of biochemical network models between different software packages. The aim is to (1) enable the enable the exchange of models between software tools with little or no human intervention, thus allowing the tools to be properly integrated; and (2) enable these models to be published in electronic form alongside, for example, peer-reviewed journal articles. The emphasis in SBML is on supporting quantitative models.

SBML model consists of a set of chemical entities linked by reactions that can transform one entity into another or transport entities between compartments. A compartment in SBML is a location having a defined size or extent (which may be in terms of volume, area, or length). Every chemical species in an SBML model must be located in a compartment. SBML can represent not only biochemical networks, but also quantitative models of interaction between these networks and other phenomena.

The Systems Biology Markup Language is formally defined in specification documents (see Question 4.2).

SBML is being developed in a series of levels, where each level adds new features and fixes problems with the previous level. The lowest-numbered levels provide fundamental features that are common to all biochemical network models. Higher-numbered levels add more features that are specific to particular classes of tools. Any level can be used as a standard for interchanging models.

The Systems Biology Markup Language (SBML): A medium for representation and exchange of biochemical network models Hucka, M., Finney, A., Sauro, H. M., Bolouri, H., Doyle, J. C., Kitano, H., Arkin, A. P., Bornstein, B. J., Bray, D., Cornish-Bowden, A. , Cuellar, A. A., Dronov, S., Gilles, E. D., Ginkel, M., Gor, V., Goryanin, I. I., Hedley, W. J., Hodgman, T. C., Hofmeyr, J.-H., Hunter, P. J., Juty, N. S., Kasberger, J. L., Kremling, A., Kummer, U., Le Novère, N., Loew, L. M., Lucio, D.

Not specifically. There is no reason why SBML models could not be stored in a database, nor is there any reason why you could not use SBML as a schema. However, this was not the motivation for creating SBML. An SBML model is meant to encode a consistent view of knowledge of a biological system. SBML is not meant to encode a large set of potentially conflicting knowledge about such a system.

The registration pages for the mailing list and the web forum are accessible from http://sbml.org/forums.

The list of tools supporting SBML has grown to over 100 at the time of this writing, and it is no longer feasible to maintain a list in this FAQ. Instead, we refer readers to the front page of the web site http://sbml.org, which gives a list of software and provides links to more information about them.

The BioModels Database provides a database of many dozens of models that have been published in the literature. The models in the database have been checked by humans to correspond to the publication and have been annotated with links to other data resources to make searching easier.

SBML Level 2 Version 1 was finalized in June 2003. SBML Level 2 Version 2 is in final draft stage and expected to be finalized in 2006. New development is oriented towards SBML Level 3.

The idea is that the units associated with every math entity in a model should be precisely defined, while at the same time allowing for reasonable default unit definitions. The set of math entities important in this regard includes variables, parameters and the result of equations.

We recommend SBML Level 2, despite the fact that at the moment more tools support Level 1, because Level 2 fixes known problems with Level 1 and we anticipate that Level 2 will be forward-compatible with Level 3.

Don't Panic. Few if any packages support all aspects of SBML. Depending on what you wish do with a model you can either ignore features that are not relevant to your tool or report errors when certain features are used. In most cases a simulator will simply report an error if it encounters a feature that it is unable to support.

SBML development has been and continues to be motivated and directed by the systems biology community. The process is managed by the SBML Editors (see next question), but they do so under the control of the community. The editors collect proposals for changes to SBML from the SBML Working Groups and from other groups and individuals, and then seek to establish a consensus in the community about how to proceed with the proposals.

These are biannual face-to-face meetings organized by the SBML editors. The formal title of the meetings is the Workshops on Software Platforms for Systems Biology. These are held in early summer and early winter. The winter meeting is normally held in conjunction with the International Conference for Systems Biology (ICSB). SBML Forum meetings allow for significant discussion of new SBML proposals and interoperability issues.

CellML is built around an approach of composing systems of equations by linking together the variables in those equations; this is augmented by features for declaring biochemical reactions explicitly, as well as encapsulating arbitrary components into modules. By contrast, SBML provides constructs that are more similar to the internal object models used in many simulation/analysis packages specialized for biochemical networks.

BioPax is a consortium that is developing a format for the exchange of pathway data between bioinformatics databases. The aim is to ensure that large subsets of data represented in one format can be converted into the other format. The BioPAX standard is designed to support a large set of biochemical entity types and types of relationships between these types. These types will be arranged into ontologies.

Interoperable Informatics Infrastructure Consortium (I3C) is an organization which promotes the use of standards in the life sciences research software. The I3C has a pathways/systems biology working group. The SBML editors are co-chairs of this working group. The I3C doesn't create standards; instead, it encourages their development and then makes recommendations on standards to its members. I3C has a close relationship with OMG.

Dr. Hamid Bolouri initially suggested it at the First Workshop on Software Platforms for Systems Biology in April 2000, held at the California Institute of Technology. The delegates there supported the idea enthusiastically.

Michael Hucka, Andrew Finney, Herbert Sauro and Hamid Bolouri wrote the original SBML proposal in the second half of the year 2000.

UK's Biotechnology and Biological Sciences Research Council and Japan's NEDO. We also had corporate support for some of the SBML workshops from The MathWorks, Inc., TERANODE Corp., and AstraZeneca.

All together, the various efforts of the SBML Team have been supported by the following organizations: the National Institutes of Health (USA); the International Joint Research Program of NEDO (Japan); the JST ERATO-SORST Program (Japan); the Japanese Ministry of Agriculture; the Japanese Ministry of Education, Culture, Sports, Science and Technology; the BBSRC e-Science Initiative (UK); the DARPA IPTO Bio-Computation Program (USA); the Army Research Office's Institute for Collaborative Biotechn.

The matrix in Table 1 lists software libraries known to support SBML. (If you know of others not listed here, please inform the editors of this FAQ.)

Given a model that doesn't contain algebraic rules it is possible to infer which components (species, compartment and parameters) are meant to be variables by examining the set of scalar rules, rate rules and reactions. However given a model containing algebraic rules knowledge of which symbols are variables and which are constants is required to solve the equations. The occurence of a symbol in an algebraic rule doesn't imply that the symbol is a variable.

Whilst it is not expected that an application will detect all errors in an parsed SBML document it is expected that a parser will not simply ignore or fudge discrepancies between the document and the relevant SBML standard. The parser should report the line number and a description of the error to the user i.e. a parser should not assume that an incorrect SBML file is an extremely unusual event or that the details of a parsing error are irrelevant to the user.

All the groups that have produced the software listed in Question 2 are involved to some extent in the development of SBML.

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