R spider

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

Abstract R spider is a web-based tool for the analysis of a gene list using the systematic knowledge of core pathways and reactions in human biology accumulated in the Reactome and KEGG databases.

R spider implements a network-based statistical framework, which provides a global understanding of gene relations in the supplied gene list, and fully exploits the Reactome (see G6G Abstract Number 20267) and KEGG knowledge-bases (KBs).

R spider provides a user-friendly dialog-driven web interface for several model organisms and supports most available gene identifiers.

R spider is available for several model organisms (Mus musculus, Rattus norvegicus, Caenorhabditis elegans, Saccharomyces cerevisiae, Arabidopsis thaliana, Drosophila melanogaster).

In addition, R spider provides the option to switch between other available public domain signaling pathway databases, such as; Nature Curated pathways and BioCarta (see G6G Abstract Number 20264).

R spider Interface --

R spider provides a simple user-friendly interface. As input it accepts several types of gene or protein identifiers, such as identifiers from Entrez Gene, UniProt/Swiss-Prot, Hugo Gene Symbols, UniGene, Ensembl, RefSeq and Affymetrix.

As output, the user obtains network models (D1, D2, and D3). The network model (D1, D2 or D3) represent a connected subnetwork with the maximal number of input genes.

R spider provides a report on the statistical significance of the inferred network models (D1, D2, D3), as well as a catalog of the enriched Reactome or KEGG pathways.

For each model (D1, D2, D3), a link is provided to obtain a graphical visualization.

The visualization is performed by the Medusa package - (see G6G Abstract Number 20299).

The manufacturers would like to point out that online visualization capabilities are limited.

For this reason, the manufacturer's recommend that you download the inferred network models as text files (links are provided on the visualization page) and use freely available packages [such as, Cytoscape - (see G6G Abstract Number 20092), Medusa] for network visualization.

Using these visualization programs can help you produce high-quality figures.

R spider Graphical output --

In the graphical output, input genes are represented by rectangles and specified by the input gene Ids. Intermediate genes are represented by triangles and specified by Entrez Gene Symbols.

Compounds are represented by circles and specified by compound names (if the length of the name exceeds 10 digits then the compound KEGG id is used).

Different colors are used to specify canonical Reactome or KEGG pathways.

In general, up to 11 of the most representative pathways (in terms of the number of genes in the model, both input and intermediate genes are counted) are colored.

In most cases, a gene can be associated to multiple pathways. For this reason, R spider implements a strict hierarchical procedure for gene coloring.

First, pathways are ordered in respect to the number of genes that are present in the model from any given pathway.

The most representative pathway will be colored in red. Colored genes (red) are excluded and pathways are reordered considering only the remaining genes.

The next most represented pathway will be colored in blue. Colored genes (red and blue) are excluded and pathways are reordered considering only the remaining genes.

This procedure will continue until 13 pathways will be colored or there will be No pathway which covers at least two (2) genes.

Therefore, colors have a strict hierarchy: red, blue, green and so on.

The number before the color indicates the hierarchy order. It is evident that some red genes may also belong to the blue (green and so on) pathway, but Not vice versa.

R spider Table: interaction context --

For each gene in the reported model, R spider provides the full interaction context. This information is summarized in the table ‘Interacting Pairs’.

In the case of Reactome, there are four (4) types of interactions: ‘direct_complex’, ‘indirect_complex’, ‘reaction’ or ‘neighboring_reaction’.

In the case of the KEGG database, interactions represent either a compound (connected genes are assigned to different reactions utilizing the same compound) or, rarely, by a reaction ID (both connected genes catalyze the same metabolic reaction).

The edge can be supported by several different interactions, all of which will be reported, and corresponding links to the source data are provided.

R spider comparison to Onto-Express --

According to the manufacturers, in comparison to other available pathway analysis tools, R spider provides a global vision of gene functional relations.

For example, submission to Onto-Express results in reporting of several (~10) enriched pathways with possibility to visualize them separately.

Onto-Express (OE) is a software package for the rapid functional profiling of a set of genes. It comprises of an annotations database and an associated web-accessible software tool.

OE creates functional profiles based on Gene Ontology (GO) for the following categories: biological processes, molecular function and cellular components.

This is certainly valuable information.

However, the best model (enriched pathway ‘Pathways in cancer’) covers 19 genes. The relation between pathways as well as the role and relation between genes that are Not covered by enriched pathways, is Not disclosed.

Thus, in comparison to Onto-Express, R spider demonstrates that genes residing in regions which frequently have a ‘copy number’ alteration in the Sézary syndrome are dependent, although they belong to a wide spectrum of signaling and metabolic pathways.

In this case the user gets a newly created pathway which covers 74 genes and actually runs through several canonical Reactome and KEGG pathways.

System Requirements

Web-based.

Manufacturer

Manufacturer Web Site R spider

Price Contact manufacturer.

G6G Abstract Number 20642

G6G Manufacturer Number 101822