BioModels Database: a public repository for sharing models of biological processes
BioModels Database is a public repository for mathematical models of biological processes. It provides access to models described in peer-reviewed scientific literature, as well as those generated automatically from pathway resources. Model components, structure, and behavior of a large proportion of models in the database are thoroughly checked. This manual procedure ensures model correspondence with the original publication. Furthermore, model components are semantically enriched with cross-references to external ontologies and other relevant data resources. Models are exported in various formats, including SBML. Graphical representations of reaction networks are also provided. Simple and advanced search options are available to facilitate model retrieval. BioModels Database can be accessed through a web interface and programmatically using web services.
All models are distributed under the terms of the Creative Commons CCO Public Domain Dedication License, ensuring that models are available free for use, modification, and distribution for any user.
BioModels Database (Li et al. 2010) hosts mathematical models of varying complexity, from simple biochemical reaction systems to larger and complex dynamic models, metabolic network models, and flux balance analysis (FBA) models. It is a part of the BioModels.net initiative (http://biomodels.net; Le Novère 2006), which aims to help modelers to exchange and integrate existing models, through the use of established and shared standards.
BioModels Database holds two major sets of models: (A) models described in scientific literature and (B) models automatically generated from pathway resources.
A. Models published in peer-reviewed scientific literature
These models are included in the resource either directly by a team of curators or after direct submission by modelers or authors. Models have also been contributed through established collaborations with other model repositories, such as the former SBML model repository (Caltech, USA), JWS Online (http://jjj.biochem.sun.ac.za), the Database Of Quantitative Cellular Signaling (DOQCS) (http://doqcs.ncbs.res.in), and the CellML Repository. More importantly, several publishers of scientific journals recommend deposition of models to BioModels Database in their author’s instruction guidelines. These include Biophysical Journal, FEBS, PNAS, Nature Publishing Group (NPG), Public Library of Science (PLoS), Royal Society of Chemistry (RSC), and BioMed Central (BMC).
Curated models: Models that satisfy the MIRIAM (Minimum Information Required in the Annotation of Models) guidelines (Le Novère et al. 2005) progress to the curated branch. These models are thoroughly checked for standard compliance, correspondence with the reference publication and reproducibility of results.
Non-curated models: Models can be in the non-curated branch for several reasons: non-MIRIAM-compliant models (e.g., they do not reproduce results published in the reference publication), pathway maps or models of networks, and models that provide insufficient quantitative results required for validation. This branch also temporarily includes models that have not yet been curated due to time or resource constraints.
Following curation and annotation (see section “Model Annotation” below), models are tagged as ready for publication and become available online with the following release of BioModels Database. Releases are scheduled two to four times a year.
Certain simulation tools support only specific Levels or Versions of SBML. For this reason, BioModels Database provides models in alternative SBML versions, in addition to the version that was used by the curators to check the model. It also provides models in a variety of other formats such as BioPAX (http://www.biopax.org/), the Virtual Cell Markup Language (VCML) (http://vcell.org/), XPPAUT (http://www.math.pitt.edu/∼bard/xpp/xpp.html), Scilab (http://www.scilab.org/), Octave (m-file) (http://www.gnu.org/software/octave/), and PDF (http://www.ra.cs.uni-tuebingen.de/software/SBML2LaTeX). Furthermore, the reaction network of the model encoded in the Systems Biology Graphical Notation (SBGN) (Le Novère et al. 2009) is available in PNG and SVG formats.
BioModels Database provides a basic online simulation using SOSlib (Machne et al. 2006). The simulation results are returned both in graphical and textual forms. An additional and more flexible simulation tool is available for many models using JWS Online. Some models are described in greater detail in the “Model of the Month.” This takes the form of a brief article discussing the biological background, significance, structure, and results of a particular model. Another important feature provided for curated models is the ability to generate sub-models from a user-selected set of model elements. These sub-models can be downloaded in SBML and used, for instance, in the modular design of new models or to expand existing models.
B. Models Generated from Pathway Resources (Path2Models)
Driven by the growing number of biochemical pathways and reconstructions, the Path2Models project (Büchel 2013) targeted the conversion of pathway information initially from KEGG (Kanehisa and Goto 2000), BioCarta (Schaefer et al. 2009), MetaCyc (Karp et al. 2000), and SABIO-RK (Wittig et al. 2012) into standard-compliant computational models.
Genome-scale metabolic reconstructions: These models are generated by extracting pathway data from the KEGG and MetaCyc databases and subjected to FBA.
Quantitative, kinetic models of metabolic pathways: These models are generated based on the metabolic pathways distributed by KEGG described as processes, in combination with experimentally determined rate laws and parameter values from the SABIO-RK database.
Qualitative, logical models of non-metabolic (primarily signaling) pathways: These models are generated based on the non-metabolic pathways distributed by KEGG, with additional information from BioCarta pathways.
In order to facilitate efficient search and enhance interpretability both by users and software tools, models are cross-linked with other database entries and terms from controlled vocabularies. Annotations are included in the models directly using Identifiers.org URIs (Juty et al. 2012). Such annotations provide a consistent and perennial way to identify model components, and an anchor which may be used to merge, or expand the scope of models.
Model Search, Browse, and Retrieval
BioModels Database provides a complete list of models available for browsing. Curated models can also be browsed based on taxonomy or Gene Ontology (GO) terms used in their annotation. Users can also search and retrieve models of interest using the annotations and related information.
BioModels Database provides web services (http://www.ebi.ac.uk/biomodels-main/webservices), allowing, for example, direct search and retrieval, and the creation of sub-models. A Web Services Description Language (WSDL) file enables software to understand available functions and their usage. The complete list of available methods, as well as a Java library and the associated documentation is provided on the BioModels Database website.
BioModels Database is developed under the GNU General Public License and the software is freely available from its SourceForge repository (http://www.ebi.ac.uk/biomodels-main/webservices).
- Büchel Fea (2013) Path2Models: large-scale generation of computational models from biochemical pathway maps. BMC Syst Biol 7:116Google Scholar