Category Cross-Omics>Pathway Analysis/Gene Regulatory Networks/Tools

Abstract BisoGenet a client-server based application for creating, visualizing and analyzing biological networks.

The system consists of three (3) tiers. In the data tier, an in-house database (SysBiomics - see below...) stores genomics information, protein-protein interactions, protein-DNA interactions, Gene Ontology (GO) and metabolic pathways.

In the middle tier, a ‘global network’ is created at server startup, representing the whole data on bioentities and their relationships retrieved from the database.

The client tier is a Cytoscape plug-in, which manages user input, communication with the Web Service, visualization and analysis of the resulting network.

BisoGenet is able to build and visualize ‘biological networks’ in a fast and user-friendly manner. A feature of Bisogenet is the possibility to include ‘coding relations’ to distinguish between genes and their products. This feature could be instrumental to achieve a finer grain representation of the bioentities and their relationships.

The client application includes ‘network analysis’ tools and interactive network expansion capabilities. In addition, an option is provided to allow other networks to be converted to BisoGenet.

This feature facilitates the integration of the manufacturer’s software with other tools available in the Cytoscape platform - (see G6G Abstract Number 20092).

The Data subsystem (data tier) --

BisoGenet's main functionality is focused on the ‘construction of networks’. Currently, the manufacturer’s ‘network model’ is based on genes, proteins and functional relationships between them such as protein-protein, protein-DNA regulatory interactions and gene-protein coding relationship.

The manufacturer's database ‘SysBiomics’ integrates heterogeneous data from multiple public domain datasets into a single and homogeneous repository. Biological entities such as genes, transcripts and proteins and their relationships define, to a large extent, the database structure.

In the SysBiomics database population phase, gene data such as chromosome localization and exon composition of each of the splicing variants are imported from Entrez Gene and NCBI Map Viewer.

Main protein information is provided by the major protein universal resource Uniprot. Protein-protein and protein-DNA interactions information is taken from the Database of Interacting Proteins (DIP), BIND, and the Human Protein Reference Database (HPRD), the Molecular INTeraction database (MINT), Intact and BioGrid.

Information on genes/proteins molecular function, biological processes and cellular component is imported from the Gene Ontology (GO) project; while information on biochemical pathways, is taken from KEGG. Additional information includes links to the databases OMIM, Unigene, PDB, Refseq, PFAM and Pubmed.

The BisoGenet Server (middle tier) --

The server subsystem (middle tier) provides the functionality for building networks. At server startup a single instance of a ‘supergraph’ is created from the data contained in the SysBiomics. The supergraph is shared by all processing threads.

This structure allows converting network construction queries into graph- based search operations. All genes and proteins of SysBiomics are represented by nodes in this graph. Genes are connected to the proteins they code for by an edge representing a ‘coding relation’.

Each protein is connected to those proteins it interacts with by an edge representing a protein-protein interaction (PPI). And finally each protein is connected to genes it interacts with; this edge represents a Protein-DNA interaction that occurs between the protein and a DNA sequence contained in the gene promoter.

The BisoGenet Client (client tier) --

The BisoGenet client is a Java desktop application designed as a Cytoscape plug-in. This application provides a user friendly interface presenting network construction options in an intuitive manner. Options specified by users are internally translated into ‘query parameters’ and sent to the server on request.

The server response is transformed into a graph and displayed on a Cytoscape window according to a custom visual style. This client-server interchange is supported on the SOAP standard web service communication protocol over HTTP.

Unlike typical three tier applications, where the client job is almost always restricted to visualization tasks, BisoGenet make use of ‘client host’ processing power and runs network analysis tools locally.

These functionalities include: finding the shortest paths between nodes, finding equivalent sets of nodes and calculating topological properties as the node degree and the cluster coefficient.

Once installed, Cytoscape adds Bisogenet as an option in its Plug-in menu.

Menu items available in the BisoGenet plug-in are “Create New Network”, “Expand Current network”, “Convert current network”, “Find shortest paths”, “Show network Statistics” and “Find equivalent nodes”.

BisoGenet Results --

BisoGenet was designed to assess the prominence of functional relations among sets of genes or proteins derived from Proteomics or Genomics experiments.

Providing a list of identifiers, choosing the kind of relations to be included and choosing a selection criterion to add nodes to the network, the end user will easily and quickly obtain a network of functional related nodes.

Node information available includes protein/gene description, GO terms and KEGG pathways with the corresponding links to external databases.

Edges information includes the sources supporting the relations between the two connected nodes with links to the database web site, the type of the ‘experimental method’ used as provided by the sources and the Pubmed references supporting the relation.

BisoGenet’s distinct feature and future --

One of BisoGenet's distinct features is the possibility of representing ‘coding relations’. Providing this capability, it is possible to represent multiple isoforms of a gene as results of alternative splicing or the coding relations of two paralogous genes coding the same protein.

With the increasing availability of information on disease-related and tissue-specific alternative splicing it is desirable to distinguish between different gene isoforms.

On the other hand, the amount of regulatory information available is also increasing, like transcription factor-gene regulation derived from ChIP-chip and ChIP-seq studies and microRNA-gene silencing relations.

One single gene can code for several microRNAs, each one targeting mRNAs transcribed by different genes. So taking all this together, incorporating ‘coding relations’ is a desirable requirement for the development of more comprehensive ‘Systems Biology’ oriented tools.

Future development of BisoGenet will focus on incorporating ‘metabolic pathway’ visualization capabilities and new graph based algorithms for adding nodes to the network.

The manufacturer also plans to add microRNA-gene silencing relations and new network analysis tools.

System Requirements

Contact manufacturer.


Manufacturer Web Site Center for Genetic Engineering and Biotechnology, BisoGenet

Price Contact manufacturer.

G6G Abstract Number 20580

G6G Manufacturer Number 104183