Reactome hits a major milestone: Reactome is now one of the largest freely accessible, open source pathway knowledgebases. Over the 10 years that Reactome has been curating and exporting pathway and reaction data, we’ve grown to include annotations for over 1/3 of the protein-coding genes in the current Ensembl human genome assembly. As of Version 50, Reactome comprises 7,642 human reactions involving the 7,597 protein products of 7,333 human genes, and 1,419 small molecules. These reactions are organized into 1,597 pathways, supported by 17,248 PubMed literature references. We have projected these reactions onto 99,812 orthologous proteins, creating 20,032 orthologous pathways in 19 model organisms.
New Pathways for this Release: Topics with revised content in V50 include Disease (Diseases associated with glycosaminoglycan metabolism), Gene expression (Transcriptional regulation by small RNAs and DNA methylation), Organelle biogenesis and maintenance (Mitochondrial translation), Signal Transduction (Hedgehog ‘off’ state), Transmembrane transport of small molecules (Orphan transporters), and Metabolism. We’d like to thank Renee Beekman, Caiyong Chen, Zofia M Chrzanowska-Lightowlers, Wolfgang Fischle, Long-Cheng Li, Yulu Cherry Liu, José I Martín-Subero, David S Rosenblatt, Dorothe Spillmann, Anna Stroynowska-Czerwinska who are our external reviewers.
In V49, Disease pathways have been expanded to include WNT in cancer, Uptake and function of anthrax toxins, and Processing-defective Hh variants abrogate ligand secretion. Metabolism now includes Aflatoxin activation and detoxification, and Immune system covers Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon. Development has been updated with EPH-EFN signaling. New pathways under signal transduction include Repression of Wnt target genes, VEGFA-VEGFR2 signaling, and Hedgehog ligand biogenesis. Updated signal transduction modules include TCF dependent signaling in response to WNT and Degradation of beta-catenin by the destruction complex. Mismatch Repair has beed added to DNA repair and Chromatin organization has been expanded to cover HDACs deacetylate histones, RMTs methylate histone arginines, and HDMs demethylate histones. Akira Kikuchi is our external author. Kurt Ballmer, Philipp Berger, Michael Edelbrock, Ernesto Guccione, Richard Hopkinson, Nancy Ip, Stephen Leppla, Shihui Liu, Yulu Liu, Anna Maria Masci, Mahtab Moayeri, Nishani Rajakulendran, Sima Salahshor, Christopher Schofield, Benjamin E Turk, Louise Walport, Michael Welsh, Jim Woodgett, and Xiang-Jiao Yang are our external reviewers.
New in V48 is Organelle biogenesis (Mitochondrial biogenesis). Topics with new or updated pathways include Cell cycle (Depolymerisation of the nuclear lamina), Cellular responses to stress (Cellular responses to heat stress, Development (Transcriptional regulation of pluripotent stem cells, Disease (Glycogen storage diseases (Myoclonic epilepsy of Lafora) and Neurotoxicity of clostridium toxins), Gene expression (Epigenetic regulation of gene expression), Metabolism of proteins (O-glycosylation of TSR domain-containing proteins and Sialic acid metabolism), and Signal transduction (TCF-dependent signaling in response to WNT. The Gallus gallus pathway Innate immune system has been updated to include Complement cascade. Luciano Di Croce, Matyas Gorjanacz, Ingrid Grummt, Angela M Lezza, Juan F Medrano, Mridul Mukherji, Bibhusita Pani, Bartholomew Pederson, Gerd Pfeifer, Nishani Rajakulendran, Yih-Horng Shiao, Renee van Amerongen, Renate Voit, Jianlong Wang, and Saumya Wickramasinghe are our external reviewers.
New in V47 is Chromatin organization (Chromatin modifying enzymes). Topics with new or revised events include Cellular response to stress (Cellular senescence and Detoxification of reactive oxygen species, Cell cycle (Condensation of prophase chromosomes), Immune system (Cell surface interaction at the vascular wall), Metabolism of proteins (Synthesis of dolichyl-phosphate), and Signal transduction (Beta-catenin independent WNT signaling). Brenda Gallie, is our external author. Tom Karagiannis, Mahendra Kavdia, Akira Kikuchi, Michelle Longworth, Shamith Samarajiwa, and Jaap Jan Zwaginga are our external reviewers.
Reactome has released a new web interface for its open-source curated database of pathways and reactions. The redesigned web site is a faster, more flexible tool to query, analyze and visualize pathway and network data. New features include:
- Access to visualization and data analysis tools via a simpler home page.
- New data model and visualization strategies to annotate and display disease counterparts of normal human processes, supporting descriptions of diseases due to infection and mutation at the molecular level.
- Revised event hierarchy panel to provide interactivity and access to the entire listing of all the Reactome pathways.
- Improved flexibility and performance of our pathway browser with a new pathway diagram visualization tool using HTML5 Canvas.
- Extended data overlaying technologies to support molecular interaction data from the PSIQUIC registry, including BindingDB, DrugBank, and GeneMANIA.
- New pathway diagram tools to search within the displayed pathway, overlay the pathway with functional interactors, and download the diagram as a snapshot or PNG file.
- Enhanced “Details” panel providing alternative displays of graphical and textual information, such as 3D structural data and citations for proteins from PDB, for small molecules from ChEBI, for the stoichiometry of metabolic reactions from Rhea, and for expression data from Gene Expression Atlas.
- Merged pathway identifier mapping, over-representation, and expression analysis tools into a tabbed data analysis portal with integrated visualization for improved pathway diagram colorization with user-supplied experimental data.
- Updated Reactome Functional Interaction plugin supports Cytoscape v3.x., providing useful tools for the discovery of network patterns related to cancer and other types of disease.
Reactome is a collaboration among groups at the Ontario Institute for Cancer Research, Cold Spring Harbor Laboratory, New York University Medical Center, and The European Bioinformatics Institute. Freely available to all users worldwide, the Reactome database offers human pathway data that span and integrate metabolism, signaling cascades, and cellular processes like apoptosis, extracted from the published literature in collaboration with experts from the scientific community and cross-referenced to a wide range of biological databases. Reactome data and software are distributed under the terms of the Creative Commons Attribution 3.0 Unported License.
New topics are Reproduction (Fertilization) and SUMOylation (Processing and activation of SUMO). Topics with new or revised events include Apoptosis (Extrinsic Pathway for Apoptosis), Binding and Uptake of Ligands by Scavenger Receptors, Cell Cycle (Nuclear Pore Complex (NPC) Disassembly), Disease (Assembly Of The HIV Virion and Budding and maturation of HIV virion), Extracellular matrix organization (Non-integrin membrane-ECM interactions and ECM proteoglycans, Immune System (Complement cascade, Cytosolic sensors of pathogen-associated DNA, and Fc epsilon receptor (FCERI) signaling), Metabolism (Metabolism of vitamins and cofactors), Signal transduction (The phototransduction cascade, Signaling by NOTCH2, Signaling by GPCR, and Signaling by Wnt).
R Belew and A Niarakis are our external authors. W Antonin, M Boutros, S Boyle, DT Bradley, M Dubé, EJ Fuentes, AK Garg, MX Ilagan, L Jin, P Lishko, CL Makino, N Venkatesan, C Neyen, C Pop, S Ricard-Blum, R Roncagalli, GS Salvesen, and J Wu are our external reviewers.
The Plant Reactome group has released 21 new rice pathways, focusing on carbohydrate biosynthesis, cofactor biosnythesis, and secondary metabolite biosynthesis.
New to Reactome is Binding and Uptake of Ligands by Scavenger Receptors. Topics with new or revised events include Immune system (Fcgamma receptor (FCGR) dependent phagocytosis), Cell Cycle (Resolution of Sister Chromatid Cohesion, Regulation of PLK1 Activity at G2/M Transition, Nuclear envelope breakdown, and Initiation of Nuclear Envelope Reformation), Extracellular matrix organization (Fibronectin matrix formation and Elastic fibre formation), Metabolism (Ubiquinol biosynthesis and cytosolic-nuclear iron-sulfur cluster biogenesis), Signal Transduction (Signaling by TGF-beta Receptor Complex, Signaling by NOTCH2, and Visual phototransduction), Transmembrane transport of small molecules (Stimuli-sensing channels), and Disease (Diseases associated with visual transduction, and Signaling by NOTCH1 in cancer). New pathway illustrations for this release include Apoptosis Extrinsic pathway and Trafficking and processing of endosomal TLRs. R Lill is our external author. J Avruch, W Blaner, V Fiorito, L He, M Kawamukai, I Mattaj, S Moestrup, J Parkinson, F Rauscher, D Reinhardt, C Rosales, Y Tanno, E Tolosano, EJ Uringa, Y Watanabe, and R Weil are our external reviewers. Plant Reactome, an integrated analysis and visualization platform for plant metabolic and regulatory pathways and networks has been released. Reactome is actively soliciting feedback through a User Survey in order to assess community needs.
Topics with new or revised events include Immune system (TLR4 cascade, MyD88:Mal cascade on plasma membrane, and MyD88-independent cascade), Cell Cycle (Condensation of prometaphase chromosomes, Mitotic prophase: MASTL facilitates mitotic progression, and Resolution of sister chromatid cohesion), Extracellular matrix organization (Collagen degradation, Elastic fibre formation, and Assembly of collagen fibrils and other multimeric structures), Metabolism (Inositol Phosphate Metabolism, Arachidonic acid metabolism, Mitochondrial Iron-Sulfur Cluster Biogenesis, and Phosphate bond hydrolysis by NUDT proteins), Signal Transduction (Signaling by Activin and Signaling by IGF1R), and Gene expression. New pathway illustrations for this release include Cell Cycle and Apoptosis. R Lill is our external author. A Burgess, YG Chen, KA Fitzgerald, F Granucci, M Holzenberger, R Ito, S Kalamajski, V Malhotra, V Mochida, L Muiznieks, J Napetschnig, S Raleigh, F Rauscher, S Ricard-Blum, TA Rouault, M Rush, T Sorsa, WH Tong, T Wundenberg, I Zanoni, and N Zhang are our external reviewers. Reactome’s SBML export (available here) has been upgraded to Level2 Version4. Our SOAP and RESTful web services, have been moved to a new server. A new series of webinars, which will introduce the Reactome website and our suite of pathway and network visualization and analysis tools, will restart in January 2013. Registration details can be found on EventBrite. A new paper, describing the extension of the Reactome data model and enhancing the web tools to permit the annotation and visualization of protein variants, anti-cancer therapeutics, and other disease processes using Reactome, was published in Cancers.
Topics with new or revised events include Immune system (STING mediated induction of type 1 IFN and DAP12 Interactions and signaling), Disease (Mucopolysaccharidoses and Signaling by PI3K/AKT in Cancer), Cell Cycle (Golgi Cisternae Pericentriolar Stack Reorganization), Metabolism (Regulation of Cholesterol Biosynthesis by SREBP), Metabolism of proteins (Metabolism of Angiotensinogen to Angiotensins), Membrane Trafficking (GLUT4 Translocation), and Gene expression. S Alves, JL Ashworth, A Colanzi, MF Coutinho, L Jin, J Joseph, A Klip, LL Lanier, G Liang, F Rauscher, L Thorpe, Y Wang, H Yuzugullu, and J Zhao are our external reviewers. New pathway illustrations for this release include Signal transduction , Signaling by Hippo, Signaling by SCF-KIT, and Mitochondrial Protein Import. Reactome is hosting two webinars, Using Reactome Pathway Database and Reactome Functional Interaction Network plugin in October. If you are interesting in participating, please register at Eventbrite. A new paper entitled Reactome – a curated knowledgebase of biological pathways: megakaryocytes and platelets has been published in the Journal of Thrombosis and Haemostasis.