Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Jan 8;48(D1):D498-D503.
doi: 10.1093/nar/gkz1031.

The reactome pathway knowledgebase

Bijay Jassal  1 , Lisa Matthews  2 , Guilherme Viteri  3 , Chuqiao Gong  3 , Pascual Lorente  3 , Antonio Fabregat  3   4 , Konstantinos Sidiropoulos  3 , Justin Cook  1 , Marc Gillespie  1   5 , Robin Haw  1 , Fred Loney  6 , Bruce May  1 , Marija Milacic  1 , Karen Rothfels  1 , Cristoffer Sevilla  3 , Veronica Shamovsky  2 , Solomon Shorser  1 , Thawfeek Varusai  3 , Joel Weiser  1 , Guanming Wu  6 , Lincoln Stein  1   7 , Henning Hermjakob  3   8 , Peter D'Eustachio  2
Affiliations

The reactome pathway knowledgebase

Bijay Jassal et al. Nucleic Acids Res. .

Abstract

The Reactome Knowledgebase (https://reactome.org) provides molecular details of signal transduction, transport, DNA replication, metabolism and other cellular processes as an ordered network of molecular transformations in a single consistent data model, an extended version of a classic metabolic map. Reactome functions both as an archive of biological processes and as a tool for discovering functional relationships in data such as gene expression profiles or somatic mutation catalogs from tumor cells. To extend our ability to annotate human disease processes, we have implemented a new drug class and have used it initially to annotate drugs relevant to cardiovascular disease. Our annotation model depends on external domain experts to identify new areas for annotation and to review new content. New web pages facilitate recruitment of community experts and allow those who have contributed to Reactome to identify their contributions and link them to their ORCID records. To improve visualization of our content, we have implemented a new tool to automatically lay out the components of individual reactions with multiple options for downloading the reaction diagrams and associated data, and a new display of our event hierarchy that will facilitate visual interpretation of pathway analysis results.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Annotating drugs: antithrombotic activity of Factor Xa inhibitors. (A) The Reactome annotation of apixaban associates it with reference information in the ChEBI (1) and IUPHAR (2) databases, with a disease process, pulmonary embolism, from the Disease Ontology (3), with a cellular component, ‘extracellular region’ from GO (4), and with literature references from PubMed (5). Each of these entries is associated with a Reactome identifier; following the link on the Reactome page takes the user to the web page for that entry in the reference database. (B) Apixiban is grouped with four other similarly annotated small molecules (1), betrixaban, endoxaban, reviroxaban and eribaxan, to form the set of Factor Xa inhibitors. (C) The shared molecular function of this set of molecules (1) is represented by annotating their binding (2) to the complex of Factors Va and Xa (3) to form an inactive complex (4), thereby negatively regulating (5) the cleavage (6) of Factor 2 (7). In our iconography, entities with a drug role are shown with their usual icon shapes but shaded purple and with an ‘Rx’ tag in the lower right corner of the icon.
Figure 2.
Figure 2.
Soliciting community input for new annotations. The new ‘external contribution’ web page is accessible via the community tab (1) at the top of the Reactome homepage. It displays a list of newly annotated, internally reviewed events for which we are seeking external reviews (2). Clicking on the [email protected] link next to an event of interest (3) opens an e-mail message (4) pre-populated with the event’s details with slots to accommodate personal details. Clicking on the event itself in the table opens a Google Document that contains a text description of the event.
Figure 3.
Figure 3.
Associating expert authors’ and reviewers’ ORCID IDs with Reactome events. (A). A search (1) on a person’s name returns a list (2) of all events (pathways and reactions) with which that person is associated as author or reviewer. Details of an individual event can be exported in BibTex (www.bibtex.org) format (3). Clicking on the ‘Are you [person]?’ text at the top of the event list opens a window in which the person can enter his or her ORCID ID and password (4). These credentials are verified and the web page that lists the events is displayed (B) with buttons (5) that enable the person to claim authored and reviewed pathways and reactions.
Figure 4.
Figure 4.
Automated reaction layout. When the details of a reaction are displayed, e.g., as the result of a search, a graphical representation of the individual reaction is generated that identifies its inputs (1), outputs (2), type (here, chemical transformation) (3), catalyst (4) and subcellular location or locations (5). The reaction image and its associated data can be exported in a variety of formats (6). Clicking on the image or the text below it takes the user to a view of the reaction in its pathway context (7).
Figure 5.
Figure 5.
Pathway browser views of the ‘Metabolism’ superpathway and its children. (A). Standard ‘fireworks’ format. (B). Voronoi diagram (‘ReacFoam’) format.
See this image and copyright information in PMC

Similar articles

  • The Reactome Pathway Knowledgebase.
    Fabregat A, Jupe S, Matthews L, Sidiropoulos K, Gillespie M, Garapati P, Haw R, Jassal B, Korninger F, May B, Milacic M, Roca CD, Rothfels K, Sevilla C, Shamovsky V, Shorser S, Varusai T, Viteri G, Weiser J, Wu G, Stein L, Hermjakob H, D'Eustachio P. Fabregat A, et al. Nucleic Acids Res. 2018 Jan 4;46(D1):D649-D655. doi: 10.1093/nar/gkx1132. Nucleic Acids Res. 2018. PMID: 29145629 Free PMC article.
  • The Reactome pathway Knowledgebase.
    Fabregat A, Sidiropoulos K, Garapati P, Gillespie M, Hausmann K, Haw R, Jassal B, Jupe S, Korninger F, McKay S, Matthews L, May B, Milacic M, Rothfels K, Shamovsky V, Webber M, Weiser J, Williams M, Wu G, Stein L, Hermjakob H, D'Eustachio P. Fabregat A, et al. Nucleic Acids Res. 2016 Jan 4;44(D1):D481-7. doi: 10.1093/nar/gkv1351. Epub 2015 Dec 9. Nucleic Acids Res. 2016. PMID: 26656494 Free PMC article.
  • The Reactome Pathway Knowledgebase 2024.
    Milacic M, Beavers D, Conley P, Gong C, Gillespie M, Griss J, Haw R, Jassal B, Matthews L, May B, Petryszak R, Ragueneau E, Rothfels K, Sevilla C, Shamovsky V, Stephan R, Tiwari K, Varusai T, Weiser J, Wright A, Wu G, Stein L, Hermjakob H, D'Eustachio P. Milacic M, et al. Nucleic Acids Res. 2024 Jan 5;52(D1):D672-D678. doi: 10.1093/nar/gkad1025. Nucleic Acids Res. 2024. PMID: 37941124 Free PMC article.
  • Plant Reactome and PubChem: The Plant Pathway and (Bio)Chemical Entity Knowledgebases.
    Gupta P, Naithani S, Preece J, Kim S, Cheng T, D'Eustachio P, Elser J, Bolton EE, Jaiswal P. Gupta P, et al. Methods Mol Biol. 2022;2443:511-525. doi: 10.1007/978-1-0716-2067-0_27. Methods Mol Biol. 2022. PMID: 35037224 Review.
  • A visual review of the interactome of LRRK2: Using deep-curated molecular interaction data to represent biology.
    Porras P, Duesbury M, Fabregat A, Ueffing M, Orchard S, Gloeckner CJ, Hermjakob H. Porras P, et al. Proteomics. 2015 Apr;15(8):1390-404. doi: 10.1002/pmic.201400390. Epub 2015 Mar 21. Proteomics. 2015. PMID: 25648416 Free PMC article. Review.
See all similar articles

Cited by

See all "Cited by" articles

References

    1. Lombardot T., Morgat A., Axelsen K.B., Aimo L., Hyka-Nouspikel N., Niknejad A., Ignatchenko A., Xenarios I., Coudert E., Redaschi N. et al. .. Updates in Rhea: SPARQLing biochemical reaction data. Nucleic Acids Res. 2019; 47:D596–D600. - PMC - PubMed
    1. Kanehisa M., Sato Y., Furumichi M., Morishima K., Tanabe M.. New approach for understanding genome variations in KEGG. Nucleic Acids Res. 2019; 47:D590–D595. - PMC - PubMed
    1. Caspi R., Billington R., Fulcher C.A., Keseler I.M., Kothari A., Krummenacker M., Latendresse M., Midford P.E., Ong Q., Ong W.K. et al. .. The MetaCyc database of metabolic pathways and enzymes. Nucleic Acids Res. 2018; 46:D633–D639. - PMC - PubMed
    1. Mi H., Muruganujan A., Ebert D., Huang X., Thomas P.D.. PANTHER version 14: more genomes, a new PANTHER GO-slim and improvements in enrichment analysis tools. Nucleic Acids Res. 2019; 47:D419–D426. - PMC - PubMed
    1. Fabregat A., Sidiropoulos K., Garapati P, Gillespie M., Hausmann K., Haw R., Jassal B., Jupe S., Korninger F., McKay S. et al. .. The reactome pathway knowledgebase. Nucleic Acids Res. 2016; 46:D649–D655. - PMC - PubMed

Publication types