Project Summary/Abstract We seek renewal of the core operating funding for The Reactome Knowledgebase. Reactome is a manually curated, peer-reviewed open access biological pathway knowledgebase that can be publicly used and redistributed by all biological research community members. The Reactome knowledgebase is used by academic, nonprofit and for-profit entities worldwide. Specifically, Reactome is employed by genomics and proteomics researchers, clinicians, geneticists, and molecular biologists to interpret the results of large-scale omics screening projects, by data scientists and bioinformaticians to develop novel approaches for knowledge discovery and mining, and by systems biologists to build predictive models of normal and disease pathways for drug discovery. Our curators, PhD-level scientists, work closely with independent investigators within the community to assemble human- and machine-readable descriptions of human biological pathways manually using dedicated software tools. Each pathway is checked and peer-reviewed prior to publication to ensure its factual accuracy and compliance with the data model. A system of evidence tracking ensures that all assertions are supported by the primary literature. Reactome uses community-standard controlled vocabularies and ontologies to increase interoperability across resources. Pathways are reviewed and updated regularly. Reactome pathways are available on our web site for browsing, downloading, and manipulation by in-house and third-party online analysis tools. The project is highly cited in the literature, has been used repeatedly to make significant biological discoveries, and is incorporated into a large number of high-impact computational tools and resources. Over the next five years, we will: (1) efficiently curate normal and disease processes, and effects of genetic variation and drugs on protein function; (2) improve pathway data analysis and input tools to increase the curation efficiency and the utility of Reactome data in large-scale biological data science projects; (3) enhance the open Reactome platform; and (4) conduct active outreach efforts to facilitate user engagement, community feedback, and adoption of Reactome.

Project Narrative Reactome is the most comprehensive open-source, open access, manually authored and peer-reviewed pathway knowledgebase. The Reactome knowledgebase and its website enable researchers, clinicians, students, and educators to find, organize, and utilize biological pathway information to support data visualization, analysis and integration.