Pathway projector: web-based zoomable pathway browser using KEGG atlas and Google Maps API

Abstract

Background: Biochemical pathways provide an essential context for understanding comprehensive experimental data and the systematic workings of a cell. Therefore, the availability of online pathway browsers will facilitate post-genomic research, just as genome browsers have contributed to genomics. Many pathway maps have been provided online as part of public pathway databases. Most of these maps, however, function as the gateway interface to a specific database, and the comprehensiveness of their represented entities, data mapping capabilities, and user interfaces are not always sufficient for generic usage.

Methodology/principal findings: We have identified five central requirements for a pathway browser: (1) availability of large integrated maps showing genes, enzymes, and metabolites; (2) comprehensive search features and data access; (3) data mapping for transcriptomic, proteomic, and metabolomic experiments, as well as the ability to edit and annotate pathway maps; (4) easy exchange of pathway data; and (5) intuitive user experience without the requirement for installation and regular maintenance. According to these requirements, we have evaluated existing pathway databases and tools and implemented a web-based pathway browser named Pathway Projector as a solution.

Conclusions/significance: Pathway Projector provides integrated pathway maps that are based upon the KEGG Atlas, with the addition of nodes for genes and enzymes, and is implemented as a scalable, zoomable map utilizing the Google Maps API. Users can search pathway-related data using keywords, molecular weights, nucleotide sequences, and amino acid sequences, or as possible routes between compounds. In addition, experimental data from transcriptomic, proteomic, and metabolomic analyses can be readily mapped. Pathway Projector is freely available for academic users at (http://www.g-language.org/PathwayProjector/).

Figure 1. Reference pathway map.

Pathway Projector provides an integrated pathway map that is based upon the KEGG Atlas, with the addition of nodes for genes and enzymes. Circles represent metabolites, and rectangles represent enzymes that are further subdivided into several compartments indicating the composite genes for heteromeric enzymes. Nodes are labeled with names or EC numbers at high zoom levels.

Figure 2. User interface.

(a) Organism selection tab lists all available organism-specific pathways, which are opened as new tabs upon selection. (b) The information window is opened by clicking on the entities represented in the map or on the markers that are shown as search results. This window shows detailed information about the selected entity, including names, images of structures, and molecular weight, and provides links to external databases. Furthermore, the selection of two metabolites as starting and ending compounds through this window results in the computation of possible paths between the two selected compounds. The result of path search is displayed in the right-most result panel and as highlighted lines on the map. (c) Data mapping, sequence similarity searches, and pathway reconstructions based on sequence data, are available in a pop-up window that can be invoked from the “Tools” button. (d) The search box located in the top-right corner automatically interprets the given query type and searches accordingly based on keywords, molecular mass, or identifiers. (e) This panel displays the search results as a list. Users can locate the entities by opening an information window, which automatically moves the map to show the selected object in the center. Links to downloadable pathway images and editing and annotation palettes are located above the search results.

Figure 3. Data mapping.

An example result and required data formats for mapping are shown. For graph mapping, the target compound ID and chart type should be defined with a colon “>ID:line”. The graph data is written on the next line and “//” is placed on the final line. For node or edge mapping, user-generated data can be input line-by line following such order by comma, ID, color, size, arrow, and label. Furthermore, details of the graph picture are shown when the graph is clicked.

Figure 4. Manual editing and annotation of pathway maps.

The pathway editing and annotation palette can be invoked from the link located at the top of the search results panel. Twenty-one pre-set icons are available to be dragged and dropped anywhere in the map, functioning as original markers. Users can freely move these markers around the map and can also add annotations and comments by clicking on the markers. Several other drawing features are available, including the line tool for drawing lines, scribble tool for free drawing, and text tool for placing labels. Brush color and size can be customized. Users can export the edited map as an XML file from the “Get XML” button, and this file can be shared and imported by other users to recapture the edited map.