The public road to high-quality curated biological pathways

Abstract

Biological pathways are abstract and functional visual representations of existing biological knowledge. By mapping high-throughput data on these representations, changes and patterns in biological systems on the genetic, metabolic and protein level are instantly assessable. Many public domain repositories exist for storing biological pathways, each applying its own conventions and storage format. A pathway-based content review of these repositories reveals that none of them are comprehensive. To address this issue, we apply a general workflow to create curated biological pathways, in which we combine three content sources: public domain databases, literature and experts. In this workflow all content of a particular biological pathway is manually retrieved from biological pathway databases and literature, after which this content is compared, combined and subsequently curated by experts. From the curated content, new biological pathways can be created for a pathway analysis tool of choice and distributed among its user base. We applied this procedure to construct high-quality curated biological pathways involved in human fatty acid metabolism.

FIGURE 1

Pathway curation workflow. This figure shows the outline of the biological pathway curation workflow. The workflow applies content from online databases, literature and experts. First, all biological information associated with the biological pathways in question is retrieved from Reactome and compared to content from KEGG, GenMAPP and BioCarta. Scientific literature is used to fill in the gaps and, finally, the results are curated with the help of experts to remove ambiguities and inconsistencies. The curated content is used to make new digital pathway representations, suitable for analysis in a pathway analysis tool of choice. These digital representations are distributed among the user base of the pathway analysis tool of choice, resulting in additional curation feedback.

FIGURE 2

Reactome to GPML pipeline. Two possible connections between Reactome and GPML are shown. Each wave block is a data type; each parallelogram is a software application. One connection uses an EBI created comma-separated text format and a novel converter to create a GPML file, a format suitable for WikiPathways and GenMAPP. Additionally, Reactome offers the option to export all its pathways and reactions as BioPAX level 2 compliant files, which can then be directly imported in the java-based Cytoscape application and converted to GPML.