DomainGraph

Category Cross-Omics>Pathway Analysis/Gene Regulatory Networks/Tools and Genomics>Gene Expression Analysis/Profiling/Tools

Abstract DomainGraph is a Java plug-in for Cytoscape (see G6G Abstract Number 20092), a software platform for the analysis and visualization of ‘molecular interaction networks’.

The main functionality of the DomainGraph plug-in is the visual analysis of the effects of alternative splicing on genes, protein isoforms, molecular interactions, pathways and miRNA binding sites.

Statistical results of Exon Array data computed with AltAnalyze (see below...) can be imported into DomainGraph and affected genes, pathways and miRNA binding sites are automatically annotated.

From these annotations, genes, ‘gene products’, and pathways can directly be loaded and visualized via DomainGraph and occurrences of alternative splicing are highlighted.

Therefore, an in-depth analysis of ‘Exon Array’ data regarding alternative splicing events and their biological impact is possible without the need of prior knowledge.

Furthermore, the detailed analysis of interaction networks and pathways is possible. Given a ‘gene interaction network’, DomainGraph visualizes the genes together with all known encoded ‘protein isoforms’ and their respective domain compositions.

Given a ‘protein interaction network’, DomainGraph decomposes the proteins into their domains and visualizes the domain interactions underlying the protein interactions. These networks can be integrated with ‘exon expression’ data produced by the Affymetrix Exon Array.

Genes, protein isoforms and domains are highlighted according to potentially occurring ‘alternative splicing’ events or ‘differential expression’ in different groups of samples.

DomainGraph's Main features/capabilities include:

1) Analysis of AltAnalyze Exon Array data with regard to genes, protein isoforms, pathways, and miRNA binding sites affected by alternative splicing. No prior knowledge of potentially affected genes or pathways required.

2) Automatic annotation and visualization of genes, Reactome (see G6G Abstract Number 20267) and WikiPathways (see G6G Abstract Number 20367), and miRNA binding sites with integrated ‘Exon Array’ data.

3) Decomposition of gene interaction networks into all known encoded protein isoforms and their domain compositions.

4) Decomposition of protein interaction networks into underlying domain interactions.

5) Integration of Affymetrix Human, Mouse, and Rat Exon Arrays (for ‘differential expression’ analysis via AltAnalyze and expression studies for single experiments).

6) Graphical view of all ‘protein isoforms’ encoded by a single gene with constituent domains, exon structures, Affymetrix probe-sets, and miRNA binding sites for convenient comparison of ‘exon expression’.

7) Annotation of microRNA binding sites for probe-sets.

8) Annotation of cross-hybridization types for probe-sets.

9) The Hypertext Markup Language (HTML) export of AltAnalyze statistics with biological annotations (genes, pathways, miRNA binding sites, alternative exon annotations) with all gene and pathway graphics.

DomainGraph's Interaction networks --

The user has to import a gene or protein interaction network of interest. DomainGraph supports the same file formats as Cytoscape for import, but users may also select a network imported via Cytoscape directly.

For a ‘gene interaction networks’, the main focus is on the encoded protein isoforms and their domain compositions. Thus, the genes are visualized together with all encoded isoforms and their domains.

For ‘protein interaction networks’, the focus is on the given protein isoforms and their underlying domain-domain interactions. The resulting network thus consists of the specific proteins, their domain compositions and the potential domain-domain interactions.

DomainGraph's Integration of Affymetrix Exon Array Data --

DomainGraph supports the analysis of ‘Single Experiment’ data as well as ‘Differential Expression’ among groups of samples. The Affymetrix Exon Expression data can be imported into the local DomainGraph database and the data is automatically mapped onto the network. Potential alternative splicing events and differential exon expression is highlighted in the network.

Single Experiment Data - This option can be used to analyze, e.g. a single tissue with regard to potentially occurring alternative splicing events. Users simply import their expression and p-value files.

These data are used to compute expression or non-expression of exons and domains. Potential alternative splicing events are highlighted in the network.

Differential Expression Data - This option is used to compare groups of samples to detect up- and down-regulation events of certain exons. Protein isoforms favored in a certain sample can thus be detected easily. Users just need to import the statistics file produced by AltAnalyze, which is specifically designed for DomainGraph.

The ‘differential expression’ data are mapped onto the network. Proteins and domains potentially affected by alternative splicing are highlighted.

DomainGraph's Visual Exploration of Expression Data --

DomainGraph provides a graphical representation of the proteins with domain architectures, the underlying exon structures, the Affymetrix Exon Array probe-sets, and microRNA binding sites.

The graphics are available for proteins and for genes, allowing for the analysis of a ‘single protein isoform’ as well as the comparison of all transcripts encoded by one gene.

Tooltips provide additional information on the domains, exons, probe-sets, and microRNA binding sites.

For ‘Single Experiment’ data, the probe-sets are colored according to their presence and absence, and expressed probe-sets are additionally colored according to the expression strength.

For ‘Differential Expression’ data, the probe-sets are colored according to whether they were analyzed or filtered out by AltAnalyze. Moreover, differentially expressed probe-sets are colored according to their up- or down-regulation in the samples.

AltAnalyze - Alternative ‘Splicing Analysis’ Tool --

AltAnalyze is a freely available program that allows you to perform array normalization of microarray data (Affymetrix CEL files), calculate basic and complex statistics and perform Pathway or Gene Ontology (GO) over- representation.

While AltAnalyze works with conventional microarrays (3' or gene arrays) it includes specialized functions for ‘exon and junction’ arrays to identify predicted ‘alternative splicing’ or ‘alternative promoter’ changes [splicing index and MiDAS (Microarray Detection of Alternative Splicing)] and view how these changes may affect protein sequence, domain composition and ‘microRNA’ targeting.

The software has an easy to use interface and requires No advanced knowledge of bioinformatics programs or scripting. It is cross-platform and works the same on any operating system.

All you will need are your microarray files along with some simple descriptions of the conditions that you're analyzing. Once analyzed, you can further view how regulated probe sets align to domains and ‘microRNA binding’ sites in the Cytoscape Plug-in DomainGraph.

System Requirements

The DomainGraph plug-in works with Cytoscape 2.6 and requires Java SE 6.

Manufacturer

Manufacturer Web Site Max-Planck-Institut für Informatik

Price Contact manufacturer.

G6G Abstract Number 20573

G6G Manufacturer Number 104039