Published online 9 November 2010 Nucleic Acids Research, 2011, Vol. 39, Database issue D691–D697 doi:10.1093/nar/gkq1018 Reactome: a database of reactions, pathways and biological processes David Croft1, Gavin O’Kelly1, Guanming Wu 2 , Robin Haw2, Marc Gillespie3, Lisa Matthews 4 , Michael Caudy2, Phani Garapati1, Gopal Gopinath5, Bijay Jassal1, Steven Jupe1, Irina Kalatskaya2, Shahana Mahajan4,6, Bruce May2, Nelson Ndegwa 1 , Esther Schmidt1, Veronica Shamovsky4, Christina Yung 2 , Ewan Birney1, Henning Hermjakob 1 , Peter D’Eustachio4 and Lincoln Stein2,7,8,* 1European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD, UK, 2Ontario Institute for Cancer Research, Informatics and Bio-Computing, Toronto, ON, M5G0A3, Canada, 3St. John’s University, College of Pharmacy and Allied Health Professions, Queens, NY 11439, 4NYU School of Medicine, Department of Biochemistry, New York, NY 10016, 5US Food and Drug Administration, Center for Food Safety and Applied Nutrition, Laurel, MD 20708, 6Hunter College, School of Health Sciences, New York, NY 10010, 7Cold Spring Harbor Laboratory, Bioinformatics and Genomics, Cold Spring Harbor, NY 11724, USA, 8University of Toronto, Department of Molecular Genetics, Toronto, ON, M5S 1A1, Canada Received September 15, 2010; Accepted October 10, 2010 ABSTRACT Reactome (http://www.reactome.org) is a collabor- ation among groups at the Ontario Institute for Cancer Research, Cold Spring Harbor Laboratory, New York University School of Medicine and The European Bioinformatics Institute, to develop an open source curated bioinformatics database of human pathways and reactions. Recently, we de- veloped a new web site with improved tools for pathway browsing and data analysis. The Pathway Browser is an Systems Biology Graphical Notation (SBGN)-based visualization system that supports zooming, scrolling and event highlighting. It exploits PSIQUIC web services to overlay our curated pathways with molecular interaction data from the Reactome Functional Interaction Network and external interaction databases such as IntAct, BioGRID, ChEMBL, iRefIndex, MINT and STRING. Our Pathway and Expression Analysis tools enable ID mapping, pathway assignment and overrepre- sentation analysis of user-supplied data sets. To support pathway annotation and analysis in other species, we continue to make orthology-based inferences of pathways in non-human species, applying Ensembl Compara to identify orthologs of curated human proteins in each of 20 other species. The resulting inferred pathway sets can be browsed and analyzed with our Species Comparison tool. Collaborations are also underway to create manually curated data sets on the Reactome frame- work for chicken, Drosophila and rice. INTRODUCTION Reactome is an open source, open access, manually curated, peer-reviewed pathway database of human pathways and processes (1). Pathway annotations are created by expert biologists, in collaboration with Reactome editorial staff and cross-referenced to proteins (UniProt) and genes (NCBI EntrezGene, Ensembl, UCSC and HapMap), small molecules (KEGG Compound and ChEBI), primary research literature (PubMed) and GO controlled vocabularies (2–9). The Reactome data model generalizes the concept of a reaction to include transform- ations of entities such as transport from one compartment to another and interaction to form a complex, as well as the chemical transformations of classical biochemistry. Entities include nucleic acids, small molecules, proteins (with or without post-translational modiﬁcations) and macromolecular complexes. This generalization permits the capture of a range of biological processes that spans signaling, metabolism, transcriptional regulation, apop- tosis and synaptic transmission in a single internally con- sistent, computationally navigable format. Reactome is an *To whom correspondence should be addressed. Tel: +1 416 673 8514; Fax: +1 416 977 1118; Email: lincoln.stein@gmail.com Correspondence may also be addressed to Peter D’Eustachio. Tel: +1 212 263 5779; Fax: +1 212 263 8166; Email: Peter.D’Eustachio@nyumc.org The authors wish it to be known that, in their opinion, the ﬁrst three authors should be regarded as joint First Authors. The Author(s) 2010. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/ by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.