The large range of features provided by BioModels Database allow users to quickly locate models of relevance for them, analyse them (and understand their structures), simulate them, extract submodels, or download them in various formats (whether text-based or graphical). These facilities are available via a web browser, or can be directly accessed from other tools by using the accompanying web services.
The most basic way of finding a particular model is to identify it from the list of available models. Links to the lists of curated models and non-curated models can be found on the homepage of BioModels Database; the same links are also available from the menu at the top of each page of the site. The lists are presented as tables whose columns display several different model characteristics; within these tabulated views, a user can sort the list of models by model identifier, model name, publication identifier or the date of last modification, by clicking the appropriate column heading.
An alternative to simply browsing the lists of models is available in the form of a tree-structured browser based on the Gene Ontology (GO) terms used in the annotation of models in the database. A navigable, pruned, subtree of GO is automatically generated by the system, allowing users to explore the database thematically. The parenthesised number that appears next to each branch of the GO tree indicates how many models within that branch contain that particular GO term. Expanding the GO tree branch allows a user to drill down to child terms and find models annotated with those more specific GO terms (Figure ). The extensive GO term coverage within BioModels Database is illustrated in Figure .
Figure 3 Models tree based on Gene Ontology. BioModels Database provides users with three primary facilities for finding and discovering models: the system's search interface, the browsable list of all models, and an alternative list based on Gene Ontology (GO) (more ...)
Figure 4 Thematic content of models. Categorisation of models in BioModels Database using the Gene Ontology (GO) terms present in each model's annotations. This chart was generated by enumerating models in the database whose annotations refer to children of the (more ...)
Search and Retrieval
BioModels Database incorporates a powerful search engine that allows users to quickly locate models of interest. In order to find relevant models, the algorithm performs several searches based on different data, then performs an inclusive disjunction (OR) to combine the results (Figure ). The searches are performed sequentially as follows: (1) querying metadata, publications and annotations, (2) searching the model bodies, and (3) searching supplementary information from external resource databases. More specifically:
Figure 5 Search engine. The BioModels Database search engine processes three different types of data in order to provide an accurate result. First, it searches the annotations (by querying the internal database), then the models (using Lucene), and finally, data (more ...)
1. The search begins with the metadata (annotations) of all models in the database. Model metadata is used to facilitate the understanding, characteristics, and management of the model. It may consist of its name, identifier, timestamp, comments from curator(s), etc. The annotations of models include publication information, authors, terms from controlled vocabularies, and links to external resources. Metadata and annotation are supposed to best reflect the nature of a model, since they represent a verified mixture of curator input and algorithmic import.
2. The next step consists of searching through the SBML files of the models. For example, the 'notes' fields are examined, as they usually contain some information describing the model elements to which they are attached.
3. Finally, because it is impractical for BioModels Database to duplicate and keep up-to-date all relevant information available from model cross-references, several external databases are searched on demand through direct connection or using web services. During this step, the search engine checks available supplementary information such as synonyms and detailed synopsis.
The system performs some post-processing of the search output in order to deliver better results for user consumption. For example, when the user performs a search using a taxonomic term, the engine traces the whole hierarchy in order to find related models. This means that a search based on the term mammalia will return not only models associated with mammalia, but also models annotated with its descendants and ancestors (Figure ). The logic of this is that a model describing, say, a system of Homo sapiens, or of Rattus norvegicus, is a model describing a system of mammalia. Similarly, a model that is valid for all metazoa or all vertebrata will be valid for mammalia too.
Figure 6 Taxonomic search. When a user's search is based on a taxonomic term, the BioModels Database search algorithm considers the entire taxonomic hierarchy. For example, searching for the term "mammalia" will catch not only models annotated with the term Mammalia (more ...)
Models can also be retrieved directly by using either of the two permanent and unique identifiers assigned to the model: the submission identifier, and the curation identifier.
The model presentation page provides access to all of the information stored about a given model, as well as all the system actions available to the user (Figure ). Elements are hyperlinked between the different views in the presentation of the model. In addition, each annotation is hyperlinked to detailed information about the annotated entity. When an annotation links to an external data resource, the contents of the linked-to resource entry are displayed in a new window in the user's web browser.
Figure 7 View of a model page. This screen image shows the interface of BioModels Database as it displays the model Kholodenko1999 EGFRsignaling (BIOMD0000000048). As illustrated here, the display of a model in the system is divided into several areas. The areas (more ...)
Within the model presentation page for a given model, the detailed description is separated into categories organised into a set of six corresponding tabs (area 3 in Figure ):
• The Model tab displays general information about the model and its creation. The uppermost region of the tab summarizes the peer-reviewed, published article that describes the model. In the region below the publication information, a link provides access to the file originally submitted, as well as information about the encoders and the dates and times of model creation and last modification. Annotations displayed with the model refer to the model as a whole and indicate such things as the biological processes being modelled or the taxonomic coverage of the model.
• The Overview tab provides quick access to all the model components, that is, the mathematical relationships, physical entities, parameters and other elements comprising the model. Users can select components of interest, and that selection is subsequently reflected when they view the other tabbed panels. Clicking 'Create a submodel with selected elements' generates a model subset containing the selected components and all the components necessary to build a valid SBML model. This submodel is displayed in a new tab, where a link is available to allow the user to download it.
• The Math tab lists all of the mathematical constructs used to describe the relationships and the time evolution of the model's variables. These constructs include reactions, events, and explicit mathematical formulae (SBML rules). Each construct is accompanied by a rendering of the mathematical equation, as well as relevant hyperlinked annotations.
• The Physical entities tab lists the spatiotemporal entities (i.e., compartments and entity pools) contained in the model, along with their initial quantities and relevant annotations.
• The Parameters tab lists all parameters used in mathematical expressions. Parameters whose scope is limited to a reaction are grouped together. Parameters whose values are determined by mathematical expressions are linked to the relevant portion of the Math tab.
• The Curation tab displays representative curation results, obtained by the curators by simulating the model under the conditions defined in the reference publication. This tab includes graphical plots and comments from the curator.
The SBML formats
menu (area 2 in Figure ) allows a user to download the model in various versions of SBML [3
]. The version used to produce the curation figures is emphasised to indicate it is the only one tested by the curators. The other SBML versions are generated by an automatic conversion process.
The Other formats
menu provides access to other (non-SBML) model representation formats, such as CellML [1
], BioPAX [31
], and the Virtual Cell Markup Language (VCML) [36
]. To permit a given model to be simulated conveniently, BioModels Database also provides downloadable configuration files for open tools such as XPPAUT [57
] and SciLab [30
]. Finally, a human-readable report in the Portable Document Format (PDF), produced using SBML2LaTeX tool [59
], is also available from the same menu.
menu provides access to graphical representations of the model's reaction networks, in the form of both static (PNG -Portable Network Graphics- and SVG -Scalable Vector Graphics-) as well as dynamic (interactive Java applet) presentations. A utility to convert graphs into the Systems Biology Graphical Notation (SBGN) [60
] is currently being developed. The Actions
menu also provides access to the online simulation tools, described below.
BioModels Database embeds SOSlib [47
] to provide a basic online simulation tool. A given model can be simulated using this facility by selecting the 'BioModels Online Simulation'
item from the Actions
menu (area 2 in Figure ). Once the user selects the species to be displayed and the duration for which the simulation should be performed, the simulation task is submitted to a computing cluster on the server side. The results of the simulation are returned in both graphical and textual form. For many models, an additional and more flexible simulation tool is available thanks to a collaboration between BioModels Database and JWS Online [61
]. The JWS Online simulation system is available from the Actions
Model of the Month
Every month, a modeller picks a model of his/her choice and writes a short article that elaborates on the model. The article places the model in its biological and theoretical background and discusses its structure and the results of its simulation. This article is then published on the BioModels Database website as a Model of the Month
]. Such articles make selected models more easily accessible to beginners, and may help them understand their context and significance.
BioModels Database provides web services with a range of features to enable other software to programmatically search and retrieve up-to-date models and their associated data, and to extract submodels [63
]. For example, tools such as the Virtual Cell [36
], CellDesigner [64
] or the Systems Biology Workbench [48
] use these services to provide their users direct access (from within their tool) to hundreds of models. The services available are defined in a Web Services Description Language (WSDL) [65
] file that enables software to easily understand available functions and their usage. BioModels Database web services use the Simple Object Access Protocol (SOAP) [66
] to encode requests and responses. This allows standardised communication through HTTP [67
] without the hindrance caused by proxies and firewalls. The complete list of available methods, as well as a Java library and the associated documentation, are provided on the BioModels Database website [68