Genomatix Pathway System (GePS)

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

Abstract The Genomatix Pathway System (GePS) is a pathway analysis system that uses information extracted from public and proprietary databases to display canonical pathways or to create and extend networks based on literature data.

More than 400 human pathways can be displayed based on data from the NCI-Nature Pathway Interaction Database - (see G6G Abstract Number 20245), Biocarta - (see G6G Abstract Number 20264), and various other sources (see Data Sources below...) which are supplemented with proprietary database content from NetPro and Genomatix in-house curated annotation such as:

GePS also allows you to create networks from an arbitrary input gene list where connections are based on literature i.e. co-citations. This gene list can be filtered by GeneRanker results, literature mining results and expression data. The resulting gene sets can be combined into new gene sets and serve as filters.

Furthermore, networks can be created from scratch without an input gene list. Genes, complexes and interactions can be simply created by clicking and dragging your mouse.

GePS also allows:

1) Overlaying experimental data either from expression arrays or from next generation sequencing (NGS) experiments;

2) Viewing experimental data under varying conditions/time-points;

3) Extending pathways and networks by the most relevant co-cited genes and transcription factor binding information; and

4) Exporting the pathways and networks in various formats including JPG, PDF, and GraphML (an XML-based format that allows for its own analyses).

GePS Network generation and extension --

Networks can be generated in three (3) ways. A network can be generated directly from a gene list by clicking on a filter/gene list in the sidebar.

You can also select several gene lists, clicking on the ‘Generate network’ button will then generate a network of the combined gene lists (‘and’/‘or’).

Furthermore, the interactions of a displayed network can be re-generated by clicking on a button in the network navigation bar e.g. with a different co-citation level or filter. A displayed network can be also extended by genes, transcription factors or transcriptional targets.

Gene lists can contain a very large number of genes and many of these genes can be co-cited. To maintain reasonable network views, there is an upper limit to the number of genes and interactions displayed.

GePS Network generation algorithms --

Literature-based networks in GePS contain a very large number of interactions between genes. Displaying all these interactions in the pathway view would render it unreadable.

Therefore a strategy is needed to reduce the number of displayed interactions without losing relevant information. To achieve this, GePS uses the simple network or the shortest path algorithm to calculate the optimal set of interactions for a network.

The simple network algorithm initially creates a network by starting with a plain list of genes. Then it iterates three (3) times over all interactions, in descending order by their number of co-citations that pass the co-citation filter.

In the first iteration the algorithms adds an interaction for two genes if both do Not have any interaction yet.

In the second iteration the algorithm adds an interaction for two genes if they are Not connected by a path. This step avoids unconnected subnetworks.

In the last iteration the algorithm adds invisible interactions if the parameter interactions per gene is Not yet fulfilled.

The shortest path algorithm initially creates a network with all genes and all interactions that could pass the co-citation filter. Then the algorithm searches for the shortest paths from the selected genes to all other genes and removes all interactions that are Not in those paths.

If No genes have been selected by the user, the algorithm selects a gene from each connected component (subnetwork in which any two genes are connected to each other by paths) with the highest number of interactions.

In GePS the weight of an interaction between two genes is determined by the number of co-citations supporting the connection - the more evidence the shorter the connection.

GePS Network extension algorithms -- A network can be extended with co-cited genes by three (3) different algorithms:

1) The algorithm “Extend by genes” extends the network by examining all genes, that are Not yet included in the current network. The algorithm starts with genes that pass the current filter, and then genes from the input list and then all other annotated genes.

In each step the genes are ranked primarily according to the number of network genes with which they are co-cited and secondarily according to the sum of all of the co-citations. The best genes are added to the network and initially for each added gene; only the interaction with the highest number of co-citations is shown.

2) “Extend by transcription factors” extends the network by adding transcription factors. In principle, it follows the same logic as ‘Extend by genes’, but considers only transcription factors.

3) The algorithm “Extend by transcriptional targets” extends the network by adding transcriptional downstream targets. In principle, it follows the same logic as ‘Extend by genes’, but has additional restrictions.

First, from the network, only transcription factors (TFs) that have a known TF binding site matrix are considered.

Second, an interaction between a gene and a network transcription factor is only considered if both are co-cited and the transcription factor has a binding site in a promoter of the gene.

Thus, for networks that do Not contain a transcription factor with a known matrix, this option cannot be applied.

GePS Additional Data sources --

1) Cancer Cell Map - is a collection of selected human-focused cellular pathways implicated in cancer, created by the Memorial Sloan-Kettering Cancer Center.

2) INOH (Integrating Network Objects with Hierarchies) is a database of higher order functional knowledge such as relationships among multiple bio-molecules that constitute signal transduction pathways or biological events in general.

3) The basal pathway data are supplemented by information collected from:

Note: BiblioSphere Pathway Edition has been replaced by the Genomatix Pathway System.

All licensed users will be able to continue to use the software until the end of their license term. The manufacturers encourage you to switch to GePS, however, as it offers the full functionality of BiblioSphere plus additional unique features.

System Requirements

Genomatix Pathway System requires Adobe Flash Player 10.1 or higher to be installed on your computer. Contact the manufacturer for additional System Requirements.

Manufacturer

Manufacturer Web Site Genomatix Pathway System (GePS)

Price Contact manufacturer.

G6G Abstract Number 20019R

G6G Manufacturer Number 101114