Networks are ideal representations for many biological processes (1
), applicable to systems such as metabolism (2
), gene regulation (3
), signal transduction (4
) and development (5
). The components, or nodes, in biological networks may represent a range of biological features of interest, such as genes, proteins, macromolecular complexes and cellular pathways. These components can be connected by different types of links, just as myriad types of interactions can connect the processes within the cell. Connections can be directed or undirected; they can have physical meaning, denote general associations; they can represent shared characteristics between components. Components can also be made up of subcomponents, in which case they are compound or modular, and the connections between modular components (or modules) can exist along with interconnections between their subcomponents (6
Choice of network representation is often dictated by the research problem at hand. Directed networks are suitable when the interactions between two components have a well-defined direction, e.g. the direction of metabolic flow from substrates to products, or the information flow from transcription factors to the genes that they regulate. Similarly, undirected networks, such as protein interaction networks, represent mutual relationships: if protein A binds to protein B, then protein B binds to protein A. This type of representation also often applies to predictions made by high-throughput proteomic or genomic analysis, or indirect links based on shared genes or protein components between pathways and complexes.
Previously, we reported a web-based application, VisANT (7
), for simultaneous visualization and overlaying of multiple types of simple network data, enabling, for example, comparisons between experimental interactions gathered from different data sets. This early version of the tool had basic capacity for visualizing and manipulating biological network information. Here, we describe significant extensions to this concept and release VisANT 2, a more general software tool for visually integrating different types biological information based on association and connectivity data. Obtainable at http://visant.bu.edu
, VisANT is free to both academic and commercial users.
The core interface of VisANT is a workbench for network analysis and visualization. Users of VisANT can upload data for any organism, such as interactions, pathways, clusters or groupings. Data can be anything that describes how genes or proteins are connected and associated, although VisANT has a controlled vocabulary for many common experimental types of data. Once uploaded, the software will display this information and allow users to (i) visually arrange, manipulate and save data in graphical form; (ii) analyze network data for topological statistics and features; and (iii) query network data for functional information from our server-side database, such as Gene Ontology (GO) function or interactions gathered from other published data sets.
In addition to simple networks, interactions in VisANT can also be defined as higher-level connections between groups of proteins, complexes, pathways or sub-networks. These ‘modular’ connections can be viewed simultaneously with connections between subcomponents, such as individual protein interactions. This complex data integration environment, therefore, significantly extends concepts of other tools, such as Cytoscape (9
), Osprey (10
) and the MINT viewer (11
), by providing for functional annotation and scientific sharing of pathway and network information viewed at multiple scales. Interaction networks and protein complexes can be viewed, e.g. within the context of GO (12
) annotations or KEGG (13
) pathway assignments. We believe this capability makes VisANT an especially useful tool for integrating information from a wide variety of sources. To accompany VisANT, we have also developed a preliminary standard for exchanging files that have visual markup and annotation of network layouts, called visML. As a network specification format, visML extends concepts of similar graph languages, such as graph markup language, but contains additional features for complex and compound network components.
Users of VisANT can input several basic data types, including data in standardized network and interaction data exchange formats, such as PSI-MI (14
) and BioPAX (http://www.biopax.org
). Development is also underway for support of the SBML (15
) pathway format. Newly supported data types include:
- Simple interactions: links defined as protein–protein, protein–DNA, gene–gene, etc.
- Modules, groups and clusters: genes, proteins, pathways, sub-networks.
- Modular interactions: complex interactions, co-localization data, shared components, pathway interactions.
Once a network data set has been imported or loaded into VisANT, the genes or proteins within it can be queried for other known and predicted interactions from published data sets, using the previously published Predictome (16
) repository. Imported interactions and components define a network ‘workspace’, which can be annotated and saved for printing or sharing among others in the community. Networks can also be analyzed for topological characteristics to identify larger global properties, such as degree distribution, path length, shortest path and clustering coefficient calculations.
Output from VisANT can be saved at any point once a network has been loaded, annotated and analyzed. There are three types of output:
- Graphical: JPEG-, PNG- and TIFF-formatted versions of the network.
- VisML: interpreted language and exchange format for storing annotation and visual layout of complex networks.
- Network statistics: statistical results and calculations of network topology.
Visual annotation of networks is saved in a computer-readable format, visML, which preserves all data, markup, formatting and layout information that a user defines for a given network. With visML, work can be saved and re-loaded later, including addition or removal of any interaction data. Complex networks can also be shared and manipulated among different users, and results from different manipulations or network views can be saved to different visML files (see ).
Workflow of visualizing and analyzing networks with VisANT.