MetScape Plugin for Cytoscape

Category Metabolomics/Metabonomics>Metabolic Profiling/Analysis Systems/Tools and Genomics>Gene Expression Analysis/Profiling/Tools

Abstract MetScape Plugin for Cytoscape provides a bioinformatics framework for the visualization and interpretation of metabolomic and expression profiling data in the context of human metabolism.

It allows users to build and analyze networks of genes and compounds, identify enriched pathways from expression profiling data, and visualize changes in metabolite data.

Gene expression and/or compound concentration data can be loaded from file(s) [in Comma-Separated Value (CSV), Tab Separated Value (TSV), or Excel formats], or the user can directly enter individual compounds/genes (using KEGG compound IDs, or Entrez Gene IDs) to build metabolic networks without loading a file.

MetScape uses an internal relational database stored at the National Center for Integrative Biomedical Informatics (NCIBI) that integrates data from the Kyoto Encyclopedia of Genes and Genomes (KEGG), the Edinburgh Human Metabolic Network (EHMN), and the NCIBI HUMDB Database.

Visualization of metabolomic network --

Visualization of metabolomic networks poses a number of challenges. Typically, metabolic networks possess a high degree of connectivity. A number of different layout algorithms had been developed for Cytoscape that attempt to minimize the crossings between the edges, the distances between nodes and the bending of the edges.

Users can easily apply Cytoscape layouts through the Cytoscape layout menu to the compound network generated by Metscape.

To start-up Metscape, users select Metscape from the plug-ins menu in Cytoscape.

The Metscape main window has three (3) tabs that provide users with the following options:

1) Load a list of compounds (compound names or KEGG IDs);

2) Load a file containing normalized experimental metabolite data with metabolite KEGG IDs and corresponding values at given time points or under specific experimental conditions; and

3) Display pathway-specific networks by choosing a pathway from the drop-down list.

Metscape can generate two (2) types of networks - a compound network, where compounds are nodes and reactions are edges, and a compound reaction network represented by a bipartite graph.

The latter consists of two types (2) of nodes, compounds (hexagons) and reactions (rectangles).

In both network styles, edges are directional. A compound node with an outgoing edge is a substrate, while a compound with an incoming edge is the product of a specific reaction.

In compound-centric networks, the reversible reactions are shown by bidirectional arrows, while in reaction-centric networks reversible (purple) and irreversible (maize) reactions can be distinguished by the node edge color.

Metscape provides two (2) network styles for users to choose before creating a network and allows users to switch between two (2) network views at any time after the network is created.

Metscape takes advantage of Cytoscape’s VizMapper to create the Metscape visual style. (VizMapper is a feature of Cytoscape that is used to show different components in a network).

User-inputted compounds are shown in blue, while the rest of the compound nodes are shown in pink. Metscape also uses a thicker node border to denote reactions with multiple enzymes.

Detailed information can be found in the Metscape legend that is displayed at the beginning of each Metscape session.

When a user hovers the cursor over a reaction node, all compounds that participate in the reaction are highlighted.

Metscape allows users to create a reaction-specific subnetwork from the highlighted compounds. Users can expand a compound network by adding reactions and compounds from the database; expanding the network will keep the current view that the original network is using.

When done, users can collapse the expanded network or restore the original network.

Interpretation of metabolomic data --

Once the network has been displayed in Metscape, users can import normalized experimental metabolite data from a tab-delimited file, where the first column always contains compound IDs. The detailed description of the format for experimental data file is contained in the Metscape documentation.

Node color and size can be used to represent two (2) different parameters simultaneously, e.g. concentration and fold change.

In order to visualize the experimentally measured changes in metabolite concentrations over time or under specific conditions, the manufacturers adopted and modified the plug-in - dynamicXpr - (A plug-in that colors nodes according to their expression across many conditions, as in a movie).

Metscape can handle up to 80 data points (conditions or time points). Users can cycle through the data points sequentially.

If the experimental values have wide range and/or the distribution of the data values is skewed, users can choose to represent the data on a log scale or rescale input data to a range from 0 to 10. This allows for better and more obvious visualized results.

Users can obtain detailed information about compounds and reactions by double clicking a node. For compounds, Metscape will display compound name, synonyms, formula, 2D structure, molecular weight, CAS number and smiles string.

Metscape also provides links to Michigan Molecular Interactions (MiMI); Human Metabolome Database (HMDB); KEGG, PubChem; ChEBI; and BioCyc.

For reactions, Metscape shows the equation, pathway, and reversibility. In addition, enzymes and genes involved in the reaction are shown.

Besides selecting a pathway from a drop-down list, Metscape provides a pathway filter that can highlight pathway-specific reactions, which can then be used to create a pathway-specific subnetwork in a new Cytoscape window.

Metscape documentation --

An extensive Metscape User Manual is available from the manufacturer’s web-site after clicking on the Help tab.

System Requirements

Contact manufacturer.

Manufacturer

Manufacturer Web Site MetScape Plugin for Cytoscape

Price Contact manufacturer.

G6G Abstract Number 20753

G6G Manufacturer Number 101826