Tissue Distribution

Traditionally, reactions in Reactome represent events that occur within a single generic human cell. It would, however, be useful to classify reactions into different human tissue types, as to provide an evolving picture of the reactions and pathways in different cell- and tissue-specific environments.

This tool (Figure 28) allows users to understand the pathways that are enriched in different human tissue types based on protein expression data.

Figure 28 Tissue selection interface in Reactome.

Tissue Selection

Tissue Distribution is launched using the Analysis button in the Pathway Browser header bar. In the Tissue Distribution section, select the one experimental tissue dataset [HPA (E-PROT-3) – Expression Atlas] in the drop-down list. Once the window refreshes, select the ‘Available Tissues’ in the left panel and hit the ‘Add’ button to add tissue expression data to the analysis tool. Press the “Add All’ button, if you would like to adjoin all the tissue expression data. Use the ‘Remove all’ and ‘Remove’ buttons to delete tissue expression data from the filter list. Once you have selected all the appropriate tissues, click the Go button to start the analysis (Figure 28).

Background operations

We have imported protein expression in different cell/tissue types from the Human Protein Atlas (HPA), overlaid these proteins on Reactome data, and extracted the subset of reactions for that particular cell type. The HPA data reflecting the expression of the protein-coding genes in 44 different human tissues can be visualized through the Analysis tools.

An over-representation analysis is performed on the protein expression data of each tissue type (explained in this section). 

Results

The results of the Tissue Distribution analysis are presented similar to that of over-representation (explained in this section). Users can use the slider at the bottom of the diagram panel to toggle between the selected tissue types. The Analysis tab in the details panel contains the enrichment statistics and the diagram panel displays reactions/pathways with overlaid tissue-specific expression data (Figure 29).

Figure 29 Results page of tissue-specific over-representation analysis.