Using the Reactome Database

Robin Haw1, Lincoln Stein1

1 Ontario Institute for Cancer Research, Toronto, Ontario, Canada
Publication Name:  Current Protocols in Bioinformatics
Unit Number:  Unit 8.7
DOI:  10.1002/0471250953.bi0807s38
Online Posting Date:  June, 2012
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There is considerable interest in the bioinformatics community in creating pathway databases. The Reactome project (a collaboration between the Ontario Institute for Cancer Research, Cold Spring Harbor Laboratory, New York University Medical Center, and the European Bioinformatics Institute) is one such pathway database and collects structured information on all the biological pathways and processes in the human. It is an expert‐authored and peer‐reviewed, curated collection of well‐documented molecular reactions that span the gamut from simple intermediate metabolism to signaling pathways and complex cellular events. This information is supplemented with likely orthologous molecular reactions in mouse, rat, zebrafish, worm, and other model organisms. This unit describes how to use the Reactome database to learn the steps of a biological pathway; navigate and browse through the Reactome database; identify the pathways in which a molecule of interest is involved; use the Pathway and Expression analysis tools to search the database for and visualize possible connections within user‐supplied experimental data set and Reactome pathways; and the Species Comparison tool to compare human and model organism pathways. Curr. Protoc. Bioinform. 38:8.7.1‐8.7.23. © 2012 by John Wiley & Sons, Inc.

Keywords: Reactome; reaction; pathway; database; biological pathway; pathway analysis; interaction network; pathway visualization

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Table of Contents

  • Introduction
  • Basic Protocol 1: Browsing a Reactome Pathway
  • Basic Protocol 2: Finding the Pathways Involving a Gene or Protein
  • Alternate Protocol 1: Finding the Pathways Involving a Gene or Protein Using UniProt (SwissProt), Ensembl, or Entrez Gene Identifier
  • Alternate Protocol 2: Using Advanced Search
  • Basic Protocol 3: Using the Reactome Pathway Analysis Tool to Annotate a Protein List with Reactome Pathway Data
  • Alternate Protocol 3: Using Pathway Analysis Tool to Identify Statistically Overrepresented Events
  • Basic Protocol 4: Using the Reactome Expression Analysis Tool to Overlay Expression Data onto Reactome Pathway Diagrams
  • Basic Protocol 5: Compare Inferred Model Organism and Human Pathways Using the Species Comparison Tool
  • Commentary
  • Literature Cited
  • Figures
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Literature Cited

   Croft, D., O'Kelly, G., Wu, G., Haw, R., Gillespie, M., Matthews, L., Caudy, M., Garapati, P., Gopinath, G., Jassal, B., Jupe, S., Kalatskaya, I., Mahajan, S., May, B., Ndegwa, N., Schmidt, E., Shamovsky, V., Yung, C., Birney, E., Hermjakob, H., D'Eustachio, P., and Stein, L. 2011. Reactome: A database of reactions, pathways and biological processes. Nucleic Acids Res. 39:D691‐D697.
   Joshi‐Tope, G., Vastrik, I., Gopinath, G.R., Matthews, L., Schmidt, E., Gillespie, M., D'Eustachio, P., Jassal, B., Lewis, S., Wu, G., Birney, E., and Stein, L. 2003. The Genome Knowledgebase: A Resource for Biologists and Bioinformaticists. Cold Spring Harbor Symposia on Quantitative Biology LXVIII:237‐244. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York.
   Kanehisa, M., Goto, S., Kawashima, S., Okuno, Y., and Hattori, M. 2004. The KEGG resource for deciphering the genome. Nucleic Acids Res. 32:D277‐D280.
   Krieger, C.J., Zhang, P., Mueller, L.A., Wang, A., Paley, S., Arnaud, M., Pick, J., Rhee, S.Y., and Karp, P.D. 2004. MetaCyc: A multiorganism database of metabolic pathways and enzymes. Nucleic Acids Res. 32:D438‐D442.
   Mi, H., Dong, Q., Muruganujan, A., Gaudet, P., Lewis, S., and Thomas, P.D. 2009. PANTHER version 7: Improved phylogenetic trees, orthologs and collaboration with the Gene Ontology Consortium. Nucleic Acids Res. 38:D204‐D210.
   Peri, S., Navarro, J.D., Amanchy, R., Kristiansen, T.Z., Jonnalagadda, C.K., Surendranath, V., Niranjan, V., Muthusamy, B., Gandhi, T.K., Gronborg, M., Ibarrola, N., Deshpande, N., Shanker, K., Shivashankar, H.N., Rashmi, B.P., Ramya, M.A., Zhao, Z., Chandrika, K.N., Padma, N., Harsha, H.C., Yatish, A.J., Kavitha, M.P., Menezes, M., Choudhury, D.R., Suresh, S., Ghosh, N., Saravana, R., Chandran, S., Krishna, S., Joy, M., Anand, S.K., Madavan, V., Joseph, A., Wong, G.W., Schiemann, W.P., Constantinescu, S.N., Huang, L., Khosravi‐Far, R., Steen, H., Tewari, M., Ghaffari, S., Blobe, G.C., Dang, C.V., Garcia, J.G., Pevsner, J., Jensen, O.N., Roepstorff, P., Deshpande, K.S., Chinnaiyan, A.M., Hamosh, A., Chakravarti, A., and Pandey, A. 2003. Development of human protein reference database as an initial platform for approaching systems biology in humans. Genome Res. 10:2363‐2371.
   Pico, A.R., Kelder, T., van Iersel, M.P., Hanspers, K., Conklin, B.R., and Evelo, C. 2008. WikiPathways: Pathway editing for the people. PLoS Biol. 22:e184.
   Schaefer, C.F., Anthony, K., Krupa, S., Buchoff, J., Day, M., Hannay, T., and Buetow, K.H. 2008. PID: The Pathway Interaction Database. Nucleic Acids Res. 37:D674‐D679.
Internet Resources
  The Biocarta human pathways project.
  BioPAX: Biological Pathways Exchange. Standardizing the file format for representing biological pathways.
  INOH: Integrating Network Objects with Hierarchies
  The Reactome home page.
  PSI‐MITAB: Proteomics Standards Initiative‐Molecular Interactions. Defining community standards for molecular interaction data representation.
  SBML: Systems Biology Markup Language. Standardizing the file format for representing models of biological pathways.
  Online version of Joshi‐Tope et al. ().
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