The pathway ontology – updates and applications

Abstract

BackgroundThe Pathway Ontology (PW) developed at the Rat Genome Database (RGD), covers all types of biological pathways, including altered and disease pathways and captures the relationships between them within the hierarchical structure of a directed acyclic graph. The ontology allows for the standardized annotation of rat, and of human and mouse genes to pathway terms. It also constitutes a vehicle for easy navigation between gene and ontology report pages, between reports and interactive pathway diagrams, between pathways directly connected within a diagram and between those that are globally related in pathway suites and suite networks. Surveys of the literature and the development of the Pathway and Disease Portals are important sources for the ongoing development of the ontology. User requests and mapping of pathways in other databases to terms in the ontology further contribute to increasing its content. Recently built automated pipelines use the mapped terms to make available the annotations generated by other groups.ResultsThe two released pipelines – the Pathway Interaction Database (PID) Annotation Import Pipeline and the Kyoto Encyclopedia of Genes and Genomes (KEGG) Annotation Import Pipeline, make available over 7,400 and 31,000 pathway gene annotations, respectively. Building the PID pipeline lead to the addition of new terms within the signaling node, also augmented by the release of the RGD “Immune and Inflammatory Disease Portal” at that time. Building the KEGG pipeline lead to a substantial increase in the number of disease pathway terms, such as those within the ‘infectious disease pathway’ parent term category. The ‘drug pathway’ node has also seen increases in the number of terms as well as a restructuring of the node. Literature surveys, disease portal deployments and user requests have contributed and continue to contribute additional new terms across the ontology. Since first presented, the content of PW has increased by over 75%.ConclusionsOngoing development of the Pathway Ontology and the implementation of pipelines promote an enriched provision of pathway data. The ontology is freely available for download and use from the RGD ftp site at ftp://rgd.mcw.edu/pub/ontology/pathway/ or from the National Center for Biomedical Ontology (NCBO) BioPortal website at http://bioportal.bioontology.org/ontologies/PW.

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“…The curation user interface allows users to capture information around genetic variants related to amino acid change, mutational impact to the protein (e.g., missense, deletion, and frameshift), and functional effect on the protein (e.g., gain-of function, and loss-of-function). In addition, gene variants can be linked to their impact on biological pathways, through the integration of a human pathway ontology from the Rat Genome Database [19]. The gene variant UI also incorporates a free-text annotation field for capture of specific information on the relationship of the variant to oncogenic transformation and protein function, which is supported by curated references from primary literature.…”

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“… “Genes in Pathway”: genes with annotations to the title term of the diagram and to child terms of the title pathway from the Pathway Ontology [2]. This is the same type of list found on the ontology term report page for the title term ( see Subheading 2.1.2, Figs.…”