Category Cross-Omics>Pathway Knowledge Bases/Databases/Tools and Cross-Omics>Knowledge Bases/Databases/Tools

Abstract BiGG is a knowledge base (KB) of Biochemically, Genetically and Genomically structured genome-scale metabolic network reconstructions.

BiGG integrates several published genome-scale metabolic networks into one resource with standard nomenclature which allows components to be compared across different organisms.

BiGG can be used to browse model content, visualize metabolic pathway maps, and export SBML files of the models for further analysis by external software packages.

Users may follow links from BiGG to several external databases to obtain additional information on genes, proteins, reactions, metabolites and citations of interest.

BiGG Construction and content --

BiGG is currently capable of browsing and exporting the contents of seven (7) different genome-scale reconstructions of six (6) organisms:

Homo sapiens Recon 1, Escherichia coli iJR 904 and iAF1260, Saccharomyces cerevisiae iND750, Staphylococcus aureus iSB619, Methanosarcina barkeri iAF692 and Helicobacter pylori iIT341.

These reconstructions span all three (3) major branches of the tree of life and include two (2) model organisms.

All reconstructions in BiGG were developed on the Genomatica Simpheny™ platform (see G6G Abstract Number 20629).

This system includes quality control features to track genes, proteins and reactions, as well as simulation tools to computationally validate models.

The models are built from a shared universal database of compounds and reactions. It is therefore Not possible to incorporate reconstructions developed with other tools.

The reconstructions are stored on a Genomatica (San Diego, CA) supplied server running an Oracle™ database.

Access to this database is provided by a read-only client with several tables and views for accessing information on Reactions, Metabolites, Genes, Proteins, Maps and Citations. All queries are performed by a Linux/Apache/Perl Server using the CGI and DBI modules.

BiGG Browsing --

The two (2) main functions of BiGG are browsing content and exporting whole reconstructions. The browser is designed for querying the content and comparing different reconstructions whereas the exporter is primarily designed to enable further computational analysis by other software packages.

The BiGG browser contains entries for metabolic reactions, metabolites, genes, proteins, and literature citations. Reaction entries contain information such as the balanced equation, compartment localization, EC number, reversibility, author comments, and links to references.

Metabolite entries contain information such as chemical formula and charge under physiological conditions. The gene-protein reaction (GPR) relationships are displayed as text or graphs using the Graphviz package.

Hyperlinks to other databases are included whenever they are provided by the authors of the reconstructions. These include NCBI Entrez gene database, Uniprot/Swissprot for genes, and KEGG and Chemical Abstracts Service (CAS) identifications for metabolites.

Reactions and metabolites can be searched through the Search Reactions and Search Metabolites pages. Reactions may be searched for by name, EC number, or associated gene.

Alternatively, all reactions in a model may be listed by using the model name as the only search parameter. It is also possible to specify compartment, pathway, or metabolite participation.

Results may be limited by only including reactions with known gene associations, high or low confidence, or by excluding transport reactions. In addition, reactions may be searched across reconstructions allowing for model comparison.

Lists of reactions matching a set of criteria may be exported as a tab delimited flat file. The exported files can contain information for multiple models, simplifying model comparison.

Metabolites may be searched for by name, KEGG ID, CAS ID, or charge. Just as for reactions, limiting searches by compartment, pathway, and organism is possible.

In addition to basic metabolite information such as formula and charge, lists of reactions in which the metabolite participates are listed and categorized by the metabolite's role as a reactant or a product.

Lists of metabolites matching a set of search criteria may be exported as tab delimited flat file, and contain information such as metabolite name, abbreviation, formula, KEGG ID, and CAS ID.

BiGG Maps --

For visualization, curated metabolic maps are provided for many organisms in BiGG. These maps show metabolites, reactions, and text markup. Some large reconstructions (in particular human Recon 1) have several maps for different metabolic subsystems.

Maps are rendered with Scalable Vector Graphics (SVG) for smooth scaling and are hyperlinked back to the entries in the database.

BiGG Exporting --

The second function of the BiGG knowledge base is exporting reconstructions as Systems Biology Markup Language (SBML) files, which are specifically designed to work with the MATLAB COBRA toolbox and the Systems Biology Research Tool for performing flux balance analysis and other computations.

This XML format is widely used for distributing systems biology models.

By default, only entries for compartments, metabolites (the "species" tag), and reactions are included. The user has several options available to customize export as detailed below.

Decompartmentalization -

A reconstruction may be exported as a decompartmentalized model. A compartment in a metabolic reconstruction is a distinct pool of metabolites and their reactions. Metabolites are exchanged among compartments by transporter reactions.

All reconstructions included in BiGG have at least two compartments: Cytosol and Extra-organism. Additionally, reconstructions of eukaryotic organisms have internal compartmentalization modeling subcellular organelles.

It should be noted that the utility of decompartmentalization lies in model comparison rather than a basis for simulations.

For instance, reactions such as ATP synthase are driven by an electrochemical gradient across compartment boundaries. In the decompartmentalized model there can be No gradients thus the ATP Synthase reaction becomes thermodynamically incorrect, creating unpredictable outcomes with some optimizations.

As a rule, decompartmentalization should only be used for comparative purposes. Computational studies should only be performed on the full models.

Associated Genes, Proteins, and Citations -

The exported SBML file may include information on genes, proteins and citations. Because the SBML specification does Not include fields for this kind of data, this information is stored in the ‘notes’ field of the reaction entries.

GPR statements -

The notes field of the Reaction entries in the exported SBML file can include Boolean strings corresponding to the GPR statements. The GPR field is read and interpreted by the COBRA toolbox but should be ignored by other programs.

From Reconstructions to Models -

Reconstructions are the basis for computational models. The process of converting a reconstruction into a model is performed by the curator. Upper and lower bounds are placed on reaction rates, bounding the space of flux distributions.

An objective function is added, often corresponding to the biomass production. The reconstruction, bounds and objective function together comprise the model exported by BiGG.

Compatibility -

SBML files conform to the level 2 version 1 specification and are compatible with the COBRA toolbox which contains many computational procedures.

Using the COBRA toolbox, the SBML file exported from BiGG may be imported as a ‘network data structure’ into MATLAB. This structure includes the stoichiometric matrix, gene and reaction information, and GPR associations.

The toolbox then allows the user to interrogate the model’s solution space using a variety of tools, including flux balance and flux variability analysis, random sampling, and robustness and gene deletion analysis.

MATLAB scripting can be used to combine methods or develop new methods Not provided in the toolbox.

The JAVA based Systems Biology Research tool (as stated above...) is another software package tested to work with the SBML files exported from BiGG.

System Requirements

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Manufacturer Web Site BiGG

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G6G Abstract Number 20628

G6G Manufacturer Number 104228