BioModels Database

Category Cross-Omics>Knowledge Bases/Databases/Tools

Abstract BioModels Database is an annotated resource of quantitative models of biomedical interest. Models are carefully curated to verify their correspondence to their source articles.

They are also extensively annotated, with (1) terms from controlled vocabularies, such as disease codes and Gene Ontology (GO) terms and (2) links to other data resources, such as sequence databases, publications, databases of compounds and pathways, controlled vocabularies, etc.

Researchers in the biomedical and life science communities can then search and retrieve models related to a particular disease, biological process or molecular complex.

Users can browse or search the database, and download the models under the Systems Biology Markup Language (SBML) format, but also various other formats, whether encoding models [CellML (see G6G Abstract Number 20294), XPP, SciLab], pathways (BioPAX) or graphs (gif or SVG).

BioModels Database differs from other "databases" (DBs) of models -- BioModels Database is Not just a repository of models, it is a true database. The models, their controlled annotation and all the related information is stored in a set of MySQL (an open source database) databases.

A user can search for particular models based on their internal components, but also extensive additional annotation. In addition, this annotation permits you to explore relevant linked resources, in order to understand better what a model is about.

BioModels Database differs from other DBs of biochemical pathways -- BioModels Database is Not a database of biochemical pathways.

First of all, its scope is larger than just biochemical events, even if, because of the current state of the field of Computational Systems Biology, those models are largely dominating the resource at the moment. Second, a quantitative model differs from a pathway in several respects:

1) A pathway does Not contain quantitative information on the amount of objects, on their behavior, and generally on their location.

2) A pathway is static, while a model can be instantiated into dynamic simulations.

3) A formal model can merge several 'biochemical reactions' into one, or, on the contrary, contain reactions without counterpart in the corresponding biological context.

The purpose is that the 'simulations' performed with the model produce quantitative results in adequation with experimental knowledge.

BioModels Database differs from Reactome -- Reactome (see G6G Abstract Number 20267) is a database of reactions and pathways, Not a database of quantititative models. The SBML files exported by Reactome (or KEGG for that matter) do Not contain any quantitative information, whether quantities (amount or concentration of species) or kinetics.

Reactome aims to describe the human cellular pathways accurately and in great details, Not to distribute abstract quantitative description of their functions.

Submission, Curation and Annotation -- Models can be submitted by anyone to the curation pipeline of the database. At present, BioModels Database aims to store and annotate models that can be encoded with SBML. CellML models are also accepted.

These model formats are synonymous with models that can be integrated or iterated forwards in time, such as ordinary differential equation models.

To be accepted in BioModels Database, a model must be compliant with MIRIAM, the Minimal Information Requested in the Annotation of Models.

One of the requirements of MIRIAM is that a model has to be associated with a reference description that provides directly, or through references, the structure of the model, the necessary quantitative parameters and presents the results of numerical analysis of the model.

BioModels Database further refines the notion of reference description, by considering only models described in the peer-reviewed scientific literature.

A series of automated tasks are performed by the pipeline prior to human intervention: 1) Verification that the file is well-formed XML; 2) If necessary, conversion to the latest version of SBML; 3) Verification of the syntax of SBML; and 4) Series of consistency checks, enforcing the validity of the model.

The last and most important step, of the curation process, is verifying that when instantiated in a simulation, the model provides results corresponding to the reference scientific article.

Examples of simulators used by the curators are CellDesigner (see G6G Abstract Number 20159), COPASI (see G6G Abstract Number 20296), Jarnac (see G6G Abstract Number 20297), MathSBML, XPP-Aut, SBMLdeSolver, SBMLeditor, and SBMLmerge.

Model components are annotated with references to relevant resources, such as terms from controlled vocabularies [Taxonomy, Gene Ontology (GO), ChEBI, etc.] and links to other databases (UniProt, KEGG, Reactome, etc.).

This annotation is a crucial feature of BioModels Database in that it permits the unambiguous identification of molecular species or reactions and enables effective search strategies.

Search and Retrieval -- The thorough annotation of models allows a 'triple search' strategy to be run in order to retrieve models of interest.

The models converted to SBML are stored directly in an XML native database, Xindice, enabling those models and/or their components to be retrieved based on the content of their elements and attributes using XPath.

For instance, the user can search for a given string of characters in the id, name and notes elements of each model component. Models can be retrieved by searching the annotation database directly, using SQL.

Although this search is quick, it requires knowing the exact identifiers used by curators to annotate a model and relate it to third party resources, such as UniProt accession, Gene Ontology Term ID, etc.

The manufacturer, therefore, implemented a more advanced search system. A user can actually search third party resources directly, such as PubMed, Gene Ontology and UniProt, for instance with 'literal text matching'.

The search system retrieves the relevant identifiers and then searches BioModels Database for the models annotated with those identifiers. As a consequence, the user can retrieve all the models dealing with ‘cell cycle’ or ‘MAPK’, without having to type ‘GO:0007049’ or ‘P27361’.

Several searches of any of the three (3) types can also be run in parallel, the results being thereafter combined with Boolean operators.

Once retrieved, the models of interest can be downloaded in SBML Level 2 format. A number of export filters are under development to provide the models in a wider range of formats.

Note: As of September 30, 2010 - The public version of BioModels Database contains 269 models in the curated and 361 in the non-curated branch. Together, these 630 models comprise 79,224 species and 109,091 reactions. Some of the existing models have been converted to SBML Level 2 Version 4, while others have been corrected with annotational updates to enhance their reusability. The database features 20,426 cross-references.

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Manufacturer

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G6G Abstract Number 20295

G6G Manufacturer Number 100859