To begin browsing the reactions contained within the DNA Repair pathway, click on the “Browse Pathways” button on the home page. Scroll down the Pathway hierarchy panel, and click on the “DNA Repair” pathway link. This will load a page corresponding to the top level of the DNA Repair pathway for Homo sapiens (Fig. 8.7.2). Click on the plus (“+”) symbol adjacent to the DNA Repair to open this level of the hierarchy, revealing the pathway subentries.
The Reactome Pathway Browser consists of four key elements:
The analyze bar, at the top of the page, provides a species selector, with a drop-down list of species. Reactome data is human-centric, data for other species is inferred from human pathways—pathway steps may be missing for other organisms if they are not identified by the inference process. Selecting an organism from the species selector will refresh the pathway browser with the inferred pathway diagram from the selected model organism, if it is conserved. The “Home” button returns the user to the Reactome homepage. The “Analyze, Annotate & Upload” button controls the interactive tools associated with the pathway diagrams.
The pathway hierarchy panel, occupying the vertical rectangle on the far left of the screen, provides a scrolling display of all Reactome canonical pathways in a hierarchy. The six headings underneath DNA Repair are the major divisions of the pathway, such as Base Excision Repair and Double-Strand Break Repair. The plus (“+”) symbol implies that there are subheadings underneath the headings. Clicking on a plus (“+”) symbol will expand the topic to show its subparts. The sub-pathways and reactions within each canonical pathway can be hidden by clicking on the minus (“−”) symbol to the left of the pathway name.
The visualization panel, to the right of the hierarchy panel, displays an interactive pathway diagram that can be panned and zoomed in Google Map style. The pathway diagram uses the conventions of the Systems Biology Graphical Notation (SBGN) format to distinguish the molecules and reactions by shape and cellular location, to provide a dynamic framework for pathway visualization and data analysis. In the top left-hand corner of the pathway diagram, there is an icon with four different-sized blue circles, which allow users to choose the zoom level and scroll across the pathway diagram. Users can also zoom using the mouse wheel, and click and drag the diagram. The thumbnail image, in the lower right corner of the visualization panel, can be used to navigate quickly to a region of interest in the pathway diagram
The details panel, below the visualization panel, contains the description of the pathway. This is the meat of the information contained within Reactome. The main screen begins with the document identifier (DOI) and stable Reactome record identifier (e.g., REACT_216.1), the authors, peer reviewers, and editors for this pathway, along with the date that the pathway was first released. This is followed by a text “summation” that describes the pathway. Below the summation are more details about the pathway, including the taxon in which the event occurs, supporting citations, the Gene Ontology classification(s) of the pathway (“Represents GO biological process”), and the cellular compartment in which the pathway is known to occur. Further down are two important fields. The field that reads “Equivalent event(s) in other organism(s)” allows one to jump to the corresponding processes in the other model organism systems. Clicking the “Participating molecules” button lists all proteins, nucleic acids, complexes and small molecules, and complexes of these entities that are involved in any of the myriad aspects of DNA Repair. Selecting a model organism from the “Compare human pathway to” drop-down menu will display an inter-species pathway-comparison view (see Basic Protocol 4 for more details). Pathway diagrams and annotations can be downloaded in a variety of formats by clicking one of the links adjacent to the “Download pathway in one of the formats” field.
Figure 8.7.2. The top-level page describing DNA Repair. The panel to the left contains an expanding hierarchical representation of the current pathway, showing the subpathways that participate in it. The interactive pathway diagram to the right is the main human-readable access point to the Reactome knowledgebase. The details panel below provides further information about the pathway.