DisGeNET overlay

Cellular pathways can be very useful to understand the molecular mechanisms of diseases. Reactome provides a feature to investigate disease-associated genes/proteins in a pathway context. This tool can be found in the Tools>Overlays>DisGeNET>Web option in the header of the website (Figure 30).

Figure 30 Location of DisGeNET overlay tool in Reactome website.

Disease Selection

This tool interface allows you to choose several parameters including gene-disease association score (from DisGeNET) or number of genes involved (Figure 31). The default results view is the voronoi, also known as ReacFoam. Analysis details can be found in the pathway browser by selecting Fireworks view for results. 

You can use the dropdown feature to select a disease of interest. For each disease, clicking on the “Analysis” button will show the results of Reactome pathway analysis with the set of genes associated with that disease.

Figure 31 Filters interface of DisGeNET overlay tool.

Background operations

DisGeNET (Pinero J, et al, Nucleic Acids Res. 2019) is a database of gene-disease associations. We have pre-processed DisGeNET curated gene-disease associations (Release v7.0) for overlay onto Reactome. This tool performs an enrichment analysis of the selected disease-specific gene set on Reactome pathways (explained in this section).

Results

The results of the DisGeNET overlay analysis are presented similar to that of over-representation (explained in this section). The Analysis tab in the details panel contains the enrichment statistics and the diagram panel displays reactions/pathways with overlaid disease-specific data (Figure 32). Pathways are coloured based on overlap significance (p-value) by default. You can use the toggle bar (bottom) in the diagram panel to colour pathways based on overlap count (coverage) instead.

Figure 32 Voronoi and pathway browser results page of DisGeNET overlay analysis of Breast_Carcinoma.