ER to Golgi

New and Updated Pathways. In version V67, topics with new or revised pathways include Gene Expression (FOXO-mediated transcription), Immune Response (ROS, RNS production in phagocytes), Neuronal System (Activation of NMDA receptors and postsynaptic events), Programmed Cell Death (Apoptotic factor-mediated response), and Signal Transduction (GPCR downstream signaling and RHO GTPase activate NADPH oxidases).

New Illustrations. Illustrations with embedded navigation features are now available for ER to Golgi Anterograde Transport, Expression and Processing of Neurotrophins, and Signaling by NTRKs.

Thanks to our Contributors. Enrico  Bertaggia, Timothy Donlon, Kasper Hansen, Oliver Nüsse, and Feng Yi are our external reviewers.

Annotation Statistics. Reactome comprises 12,788 human reactions organized into 2,256 pathways involving 25,417 proteins and modified forms of proteins encoded by 10,792 different human genes, 1,827 small molecules, and 155 drugs. These annotations are supported by 29,454 literature references. We have projected these reactions onto 139,298 orthologous proteins, creating 21,374 orthologous pathways in 18 non-human species. Version 67 has annotations for 1,564 protein variants (mutated proteins) and their post-translationally modified forms, derived from 299 proteins. These have been used to annotate 506 complexes and 962 disease-specific reactions organized into 467 pathways and subpathways, and tagged with 342 Disease Ontology terms.

About the Reactome Project. Reactome is a collaboration between groups at the Ontario Institute for Cancer Research, Oregon Health and Science University, New York University Langone Medical Center, and The European Bioinformatics Institute. Reactome annotation files and interaction data derived from Reactome are distributed under a Creative Commons Public Domain (CC0 1.0 Universal) Licence. A Creative Commons Attribution 4.0 International (CC BY 4.0) Licence will apply to all software and code, database data dumps, and Pathway Illustrations (Enhanced High-Level Diagrams), Icon Library, Art and Branding Materials. A full description of the new and updated content is available on the Reactome website.

Follow us on Twitter: @reactome to get frequent updates about new and updated pathways, feature updates, and more!

For more information. Please contact our This email address is being protected from spambots. You need JavaScript enabled to view it..

ReactomeFIViz GSEA

ReactomeFIViz is a Cytoscape app built upon Reactome pathways to help users perform pathway- and network-based data analysis and visualization. One of the most popular approaches to pathway analysis, which is an alternative to the traditional gene-list based pathway enrichment, is Gene Set Enrichment Analysis (GSEA). GSEA considers all genes with their scores based on a weighted Kolmogorov–Smirnov-like test and is a representative approach of second-generation pathway analysis. ReactomeFIViz implements features to perform GSEA analysis using Reactome pathways for a gene score file. 

More details about the GSEA feature and the ReactomeFIViz app can be found here

OpenAccess Week: GraphDB and ContentService

Since version 57 we provide our data in a Neo4j graph database helping to reduce the complexity of the represented knowledgebase and allowing a more straightforward access to our content. Neo4j’s query language, Cypher, allows queries to be written in a more intuitive way and reduces the average response time per query by 93% (Fabregat et al., 2018).

The graph database also benefits Reactome in other aspects like (i) the creation of complex data quality assessment (QA) queries or (ii) supporting software that requires data pattern analysis, e.g. reactions classification. QA queries are executed during each quarterly release to identify instances that need to be checked out and corrected by Reactome curators ensuring that high-quality content is delivered to the final user. The reactions classifier project, for example, uses Cypher to formalise the concepts presented in Jupe et al. (2014) to generate a series of reports that help curators classify the reactions in Reactome.

The Content Service constitutes an easy API, based on the Representational State Transfer (REST) protocol, that provides access to the Reactome knowledgebase. It includes a set of methods classified in groups according to their functionality. For instance, expanding the pathways group reveals a set of methods that provide specific information about pathways such as the contained Events or the participating PhysicalEntities.

OpenAccessWeek Textbook-like illustrations and icon library

Textbook-like illustrations aim to improve the graphical representation of higher-level pathways in the Reactome events hierarchy, e.g., “signal transduction”, “apoptosis”, or “metabolism of proteins” whose pathway diagrams consisted of green boxes labeled with the names of sub-events, optionally located in cellular compartments and connected by arrows. These green-box diagrams feature limited navigation: clicking on a green box takes the user to that sub-event.

There was a general agreement that green-box diagrams are not that appealing, and put off users accustomed to textbook-quality illustrations of biological processes with striking, intuitively clear iconography. The project includes generation of scalable vector graphic (SVG) versions of illustrations, and a diagram module that makes these images interactive by enabling actions such as hovering over the items or selecting them to show the associated content in the details panel.

Developing this project has also driven the creation of the Icon Library; a consistent iconography compendium that ranges from simple protein labels to representations of organelles, receptors and cell types. The library has now been integrated in the main search as well as in the pages of their associated entities such as proteins or chemicals. Icons can be found by their name, description, designer and/or contributor.

The Icon Library is freely accessible (under a CC-BY 4.0 licence) and it is suitable for a broad range of purposes, from schematic pathway sketches in scientific presentations and publications to grant proposal illustrations. As the library was created to be a community resource, the invitation for third parties to contribute is still open. Aiming to achieve technical and artistic consistency, detailed guidelines are provided at https://reactome.org/icon-info. To acknowledge the community engagement, each icon is attributed to the author through a metadata file linking to a portfolio and/or ORCID id. As of September 2018, the library has considerably grown to 1,150 components.

20181024 OpenAccess week ReactomeFIViz 2

As part of the International Open Access week, we would like to talk about another one of our open access network visualization and analysis tool – the Reactome FIViz app.

In order to improve our understanding of disease mechanisms and develop better personalized precision therapies for patients, many biological and clinical studies employ high-throughput techniques that generate large-scale data sets. Typically, these data sets are gene- or protein-based, and to better understand the relationships among interesting genes or proteins, researchers usually have to project them onto biological network contexts to provide holistic visualization and analysis platform for reducing the dimensionality of data using network modules.

To assist our users who would like to perform network-based analysis, we have constructed the Reactome Functional Interaction (FI) network which, covers 60% of the total human protein-coding genes, and was created by extracting interactions from manually curated pathways and predicting interactions based on a machine learning technique. We have developed the Cytoscape application (or app), called the “ReactomeFIViz” that uses this highly reliable FI network to support network-based data visualization and analysis. Users of our app can construct an FI subnetwork for a list of genes, perform network clustering to find network modules, annotate the subnetwork and modules, and perform survival analysis for network modules. Furthermore, the app can also perform pathway enrichment analysis using a gene score file, and pathway mathematical modeling based on probabilistic graphical models and Boolean networks. More documentation about the ReactomeFIViz app is available through our User Guide and the Cytoscape App Store.

International Open Access week (Analysis Tools)

Following up on the International Open Access week, we would like to remind our users that all our tools, including the analysis, are open access.

Pathway analysis methods have a broad range of applications in physiological and biomedical research. Our analysis suite currently implements an overrepresentation analysis, an expression data analysis and a species comparison tool. Using this service, users can submit their sample (list of identifiers) to get as result the most significants pathways. Results are overlaid in the different modules of our Pathway Browser and can be exported to different formats including a PDF report.

A light-weight client is integrated in our Pathway Browser. The tool suite is available via a RESTFul Web Service so all the available analysis tools can be easily integrated into third party software. More documentation for developers is available at our developer's zone.

SBGN Revamp

The Systems Biology Graphical Notation (SBGN) project is an effort to standardise the graphical notation used in maps of biological processes. It aims to communicate biological knowledge more efficiently and accurately between different research communities in the life sciences.

Following this commitment, we’ve recently revamped our SBGN export methods and tools to provide more accurate representation of our pathway diagrams. Users have the option to either export a pathway diagram in SBGN through the PathwayBrowser, or get all human pathway diagrams from our downloads section.

Our PathwayBrowser now features advanced search capabilities powered by Solr to allow finding content throughout the whole knowledgebase. The user interface has been improved adapting to the findings of our last UX testing. The search within the Diagram Viewer widget enables users to define the scope of their search either limiting it to the content of the displayed diagram or expanding it to cover all pathways allowing our users to perform a search against all content without having to go the main search.

This new feature has also been enabled in our diagram and pathways overview widgets so third party web applications can already take advantage of it, allowing users to search Reactome content without abandoning the page they are in.

The new search features:

  1. Suggestions based on the introduced term.
  2. Listing the most recent searches.
  3. Scoping results to either the displayed diagram or the whole database.
  4. Filtering results by one or more entity types (i.e. Proteins, Chemical compounds, Reactions, etc.)
  5. Flagging a given entity to persist its highligthing.

To learn more, please check the Searching Reactome section in our User Guide.

protein localization

New and Updated Pathways. In version 66, topics with new or revised pathways includeDisease (Loss of function of MECP2 in Rett syndrome and Defective Base Excision Repair Associated with MUTYH), Gene Expression (Transcriptional regulation by MECP2), Immune Response (OAS antiviral response), Metabolism of proteins (SUMOylation of DNA methylation proteins, SUMOylation of immune response proteins, SUMOylation of intracellular receptors, SUMOylation of SUMOylation proteins, SUMOylation of transcription cofactors, and SUMOylation of ubiquitinylation proteins), and Signal Transduction (Signaling by Erythropoietin).

Thanks to our Contributors. John Christodoulou, Rahul Krishnaraj, Kathy L McGraw, Marco Meras-Rios, Yusaku Nakabeppu, Einari Niskanen, Robert H Silverman, and Jürgen Wienands are our external reviewers.

New Ilustrations. Illustrations with embedded navigation features are now available for DNA replication and Protein localization.

Annotation Statistics. Reactome comprises 12,047 human reactions organized into 2,244 pathways involving 11,049 proteins encoded by 10,870 different human genes, 1,948 small molecules, and 11,823 complexes. New in this release are annotations of the functions of 139 drugs, 3 of them proteins and 136 small molecules. These annotations are supported by 28,829 literature references. We have projected these reactions onto 139,072 orthologous proteins, creating 21,283 orthologous pathways in 18 non-human species. Version 66 has annotations for 1,391 protein variants (mutated proteins) and their post-translationally modified forms, derived from 293 proteins, which have been used to annotate disease-specific complexes, reactions and pathways.

About the Reactome Project. Reactome is a collaboration between groups at the Ontario Institute for Cancer Research, Oregon Health and Science University, New York University Langone Medical Center, and The European Bioinformatics Institute. Reactome annotation files and interaction data derived from Reactomeare distributed under a Creative Commons Public Domain (CC0 1.0 Universal) Licence. A Creative Commons Attribution 4.0 International (CC BY 4.0) Licence will apply to all software and code, database data dumps, and Pathway Illustrations (Enhanced High-Level Diagrams), Icon Library, Art and Branding Materials. A full description of the new and updated content is available on the Reactome website.

Follow us on Twitter: @reactome to get frequent updates about new and updated pathways, feature updates, and more!

For more information. Please contact our This email address is being protected from spambots. You need JavaScript enabled to view it..

Google Data Search

We are pleased to announce that we are amongst the early adopters of the new Google Dataset Search.

Throughout the world, there are many thousands of open access data repositories hosted by public institutions, research projects, local and national governments, not-for-profit organisations, and many others. These online resources provide a variety of datasets, which are available in different formats and support many data standards. The Google Dataset Search engine enables easy access to these datasets, so that researchers, scientists, data journalists, data wranglers, or anyone else can quickly find the data for their work.

An example of how Reactome pathway data can be viewed in the Google DataSet Search is available at this link.

Analysis Report PDF

We now offer a new tool to download your analysis results as a single PDF file. This report contains a genome-wide overview, statistics for the most significant pathways and, for each significant pathway, it includes the corresponding diagram image with the analysis overlaid, a summation of the pathway, the related bibliography and the list of identifiers found.

When performing pathway analysis through our PathwayBrowser, you can download the report by clicking on the “Report (PDF)” button on the bottom-left corner of the Analysis tab. This feature is also available when implementing programmatic access to our AnalysisService through this method.

carbohydrate

New and Updated Pathways. In version V65, topics with new or revised pathways include Immune System (Interleukin-9 signalingand Signal Transduction (Signaling by NOTCH4 and Signaling by NTRK3 (TRKC)). Illustrations with embedded navigation features are now available for Carbohydrate Metabolism and Homology Directed Repair.

Thanks to our Contributors. Jorge Azevedo, Antonio Gómez-Outes, Jan HaavikEun-Kyeong Jo, Paula Licona-Limon, Jared Rutter, and Pantelis Tsoulfas, are our external reviewers.

Annotation Statistics. Reactome comprises 11,896 human reactions organized into 2,222 pathways involving 10,935 proteins encoded by 10,763 different human genes, 1,880 small molecules, and 11,674 complexes. These annotations are supported by 28,436 literature references. We have projected these reactions onto 159,163 orthologous proteins, creating 23,450 orthologous pathways in 18 non-human species. Version 65 has annotations for 1,339 protein variants (mutated proteins) and their post-translationally modified forms, derived from 289 proteins, which have been used to annotate disease-specific complexes, reactions and pathways.

About the Reactome Project. Reactome is a collaboration between groups at the Ontario Institute for Cancer Research, Oregon Health and Science University, New York University Langone Medical Center, and The European Bioinformatics Institute. Reactome annotation files and interaction data derived from Reactome are distributed under a Creative Commons Public Domain (CC0 1.0 Universal) Licence, A Creative Commons Attribution 4.0 International (CC BY 4.0) Licence will apply to all software and code, database data dumps, and Pathway Illustrations (Enhanced High-Level Diagrams), Icon Library, Art and Branding Materials. A full description of the new and updated content is available on the Reactome website.

Follow us on Twitter: @reactome to get frequent updates about new and updated pathways, feature updates, and more!

For more information. Please contact our This email address is being protected from spambots. You need JavaScript enabled to view it..

Digest Absorp

New and Updated Pathways. In version V64, topics with new or revised pathways include Signal Transduction (ESR-mediated signaling and Signaling by NTRK2), Metabolism (Biosynthesis of specialized proresolving mediators (SPMs)), and Metabolism of proteins (Peroxisomal protein import).

Thanks to our Contributors. Hanna Antila, Jorge Azevedo, Kumar Belani, Gerry Boss, Matthew Brenner, Eero Castrén, Arthur Cooper, Diana Downs, Marc Fransen, Trond Hansen, Hui-Chih Hung, Margaret James, Pidder Jansen-Duerr, Hideo Kimura, Luca Magnani, Steven Patterson, Paul  Van Veldhoven, Alexander Weiss, and Herman Wolosker are our external reviewers.

Illustrations with embedded navigation features are now available for Digestion and absorption, DNA Double-Strand Break Repair, Signaling by receptor tyrosine kinases, Signaling by FGFR, MAPK family signaling cascades, MAPK1/MAPK3 signaling, Signaling by TGF-beta family, RHO GTPase Effectors, Signaling by Wnt, Signaling by Hedgehog, Death Receptor Signaling, and Intracellular signaling by second messengers.

Annotation Statistics. Reactome comprises 11,754 human reactions organized into 2,216 pathways involving 11,030 proteins encoded by 10,762 different human genes, 1,867 small molecules, and 11,561 complexes. These annotations are supported by 28,254 literature references. We have projected these reactions onto 140,720 orthologous proteins, creating 21,223 orthologous pathways in 18 non-human species. Version 64 has annotations for 1,339 protein variants (mutated proteins) and their post-translationally modified forms, derived from 289 proteins, which have been used to annotate disease-specific complexes, reactions and pathways.

About the Reactome Project. Reactome is a collaboration between groups at the Ontario Institute for Cancer Research, Oregon Health and Science University, New York University Langone Medical Center, and The European Bioinformatics Institute. Reactome annotation files and interaction data derived from Reactome are distributed under a Creative Commons Public Domain (CC0 1.0 Universal) Licence, A Creative Commons Attribution 4.0 International (CC BY 4.0) Licence will apply to all software and code, database data dumps, and Pathway Illustrations (Enhanced High-Level Diagrams), Icon Library, Art and Branding Materials. A full description of the new and updated content is available on the Reactome website.

Follow us on Twitter: @reactome to get frequent updates about new and updated pathways, feature updates, and more!

For more information. Please contact our This email address is being protected from spambots. You need JavaScript enabled to view it..

DNA repair

New and Updated Pathways. In version V63, topics with new or revised pathways include Immune System (Interleukin-20  family signalingInterleukin-21 signalingInterleukin-37 signaling, and other Interleukin signaling), Metabolism (Vitamin D (calciferol) metabolism), and Signal Transduction (Signaling by NOTCH3). Illustrations are now available for DNA RepairBase Excision RepairSignaling by GPCR,  GPCR ligand binding,  GPCR downstream signaling, and Translation.

Thanks to our Contributors. Laurence BindoffRoberta CarrieroSandip DattaCecilia GarlandaElzbieta GlaserMichael HolickTony Kouzarides , Alberto Mantovani, and Birgit Meldal are our external reviewers.

Annotation Statistics. Reactome comprises 11,426 human reactions organized into 2,179 pathways involving 10,996 proteins encoded by 10,739 different human genes, 1,764 small molecules, and 11,366 complexes. These annotations are supported by 27,694 literature references. We have projected these reactions onto 138,985 orthologous proteins, creating 20,932 orthologous pathways in 18 non-human species. Version 63 has annotations for 1,334 protein variants (mutated proteins) and their post-translationally modified forms, derived from 287 proteins. These have been used to annotate 506 disease-specific complexes and 906 disease-specific reactions organized into 453 pathways and subpathways, and tagged with 294 Disease Ontology terms.

About the Reactome Project. Reactome is a collaboration between groups at the Ontario Institute for Cancer Research, Oregon Health and Science University, New York University Langone Medical Center, and The European Bioinformatics Institute. Reactome annotation files and interaction data derived from Reactome are distributed under a Creative Commons Public Domain (CC0 1.0 Universal) Licence,. A Creative Commons Attribution 4.0 International (CC BY 4.0) Licence will apply to all software and code, database data dumps, and Pathway Illustrations (Enhanced High-Level Diagrams), Icon Library, Art and Branding Materials. A full description of the new and updated content is available on the ,..

Follow us on Twitter: @reactome to get frequent updates about new and updated pathways, feature updates, and more!

For more information. Please contact our This email address is being protected from spambots. You need JavaScript enabled to view it..

Creative Commons Zero - CC0

Since our inception, we have been an open source and open access resource,  free for use by anyone under the terms of a Creative Commons Attribution 4.0 International (CC BY 4.0) license. This license granted parties the non-exclusive right to use, distribute and create derivative works based on Reactome, provided that the works are correctly attributed to OICR, NYUMC, EBI, and OHSU.

In line with the growing movement to provide free open data in the public domain, and to better support the needs of our user community, we are updating the licensing agreement for some of our web content and data to reflect the Creative Commons Public Domain (CC0). CC0 is the "no copyright reserved" option in the Creative Commons toolkit. It effectively means relinquishing all copyright and similar rights that we hold in a work and dedicating those rights to the public domain.

A Creative Commons Public Domain (CC0 1.0 Universal) Licence will now cover all Reactome annotation files, e.g. identifier mapping, specialized data files, and interaction data derived from Reactome.

A Creative Commons Attribution 4.0 International (CC BY 4.0) Licence will continue to apply to all software and code, e.g. relating to the functionality of the reactome.org, derived websites and webservices, the Curator Tool, the Functional Interaction application, SQL and Graph Database data dumps, and Pathway Illustrations (Enhanced High-Level Diagrams), Icon Library, Art and Branding Materials.

For information about how to properly credit data use, please review the Reactome License and the Creative Commons FAQ, or contact the This email address is being protected from spambots. You need JavaScript enabled to view it..

20171115 NAR Paper 2017

A new research article titled “The Reactome Pathway Knowledgebase” has been published in the forthcoming 2018 NAR Database Issue. The paper describes the deployment of a Neo4J graph database on our production server, development of a new high-performance in-memory implementation of our overrepresentation data analysis tool, improvements to the Pathway Diagram Viewer, and implementation of the new Enhanced High Level Diagrams (EHLDs). More publications from the Reactome Team can be found here.

new logo

As part of the ongoing evolution of our website, we are proud to announce the launch of our new logo. Reactome has grown and evolved over the last 14 years, and we felt it was time for a change.

The new logo brings to the forefront the value and quality of the information and analysis tools that can be found in our curated database of pathways. The layering in our logo highlights the transparency of Reactome’s nature while the rounded typography matches our openness.

Derived from a shape that exists in nature and at the same time gives structure, the logo evokes the idea of discovering by unwrapping the layers of knowledge that surround biological events.

We have refreshed our logo to reflect who we are today and to symbolize our dynamic future. Rest assured though: our high-quality data and services, and our dedication to you will remain the same!

For more information, please go to Our Logo.

Responsive Reactome 2

We’ve launched our new website and are excited to introduce you to our new look! Reactome is inviting its users to explore its new website. The new website has been designed to provide the ultimate user-friendly experience with improved navigation and functionality throughout. Created with the user experience firmly in mind, the new web interface has been designed using the latest technology, so the site is compatible with today's browsers and mobile devices. The site includes extensive documentation to help users understand Reactome’s complete range of tools for viewing pathway diagrams, analyzing experimental data and exploring protein-protein interaction networks. For software developers, our technical documentation and use cases provide a detailed overview of our extensive web services, to access our curated pathway data (ContentService) and analytical tools (AnalysisService). Biologists and bioinformaticians can now benefit from richer online content that is easier to navigate and share with others, assisting with pathway data analysis and visualization.

New and Updated Pathways. In version V62, topics with new or revised pathways include Developmental biology (Signaling by Robo receptor), Gene expression  (Transcriptional regulation by E2F6  and Transcriptional regulation by RUNX2), and Immune System (Interleukin-7 family signaling, Interleukin-15  family signalingInterleukin-35  family signaling, and Interleukin-38  family signaling). Illustrations are now available for Aquaporin-mediated transportCellular senescenceEpigenetic regulation of gene expressionGene ExpressionNegative epigenetic regulation of rRNA expressionO2/CO2 exchange in erythrocytesPeptide hormone metabolism, Positive epigenetic regulation of rRNA expressionPost-translational protein modificationResponse to metal ionsSignal Transduction, and SLC-mediated transmembrane transport.

Thanks to our Contributors. Patricia Ducy is our external author. Patricia DucyJorg GoronzyAnna HerlihyAlexander  JaworskiUmesh  KumarJavier Francisco MoraManoj PatidarYuliya  Pylayeva-GuptaKailash Singh, and Ren Sun are our external reviewers.

Annotation Statistics. Reactome comprises 11,302 human reactions organized into 2,176 pathways involving 10,878 proteins encoded by 10,712 different human genes, 1,768 small molecules, and 11,284 complexes. These annotations are supported by 27,526 literature references. We have projected these reactions onto 121,709 orthologous proteins, creating 20,854 orthologous pathways in 18 non-human species. Version 62 has annotations for 1,334 protein variants (mutated proteins) and their post-translationally modified forms, derived from 285 proteins. These have been used to annotate 506 disease-specific complexes and 906 disease-specific reactions organized into 453 pathways and subpathways, and tagged with 294 Disease Ontology terms.

About the Reactome Project. Reactome is a collaboration between groups at the Ontario Institute for Cancer Research, Oregon Health and Science University, New York University Langone Medical Center, and The European Bioinformatics Institute. Reactome data and software are distributed under the terms of the Creative Commons Attribution 4.0 License. A full description of the new and updated content is available on the Reactome website.

Follow us on Twitter: @reactome to get frequent updates about new and updated pathways, feature updates, and more!

For more information. Please contact our This email address is being protected from spambots. You need JavaScript enabled to view it..

SBML

As part of our efforts to give our modeling user community better experience, we have updated the SBML export to Level 3 Version 1, which is organized in a modular manner.  Our initial export provides a richer annotation  syntax and we will explore supporting other SBML Level 3 Packages in the future. The SBML data export can be used by any tool that supports SBML L3V1.

The SBML Level 3 Version 1 export is available for download here: https://reactome.org/download/current/homo_sapiens.3.1.sbml.tgz.

We are also providing a programmatic interface to access these updated SBML files through our ContentService for all species at https://reactome.org/ContentService/#!/exporter/toSBMLUsingGET

Reactome is a collaboration between groups at the Ontario Institute for Cancer Research, Cold Spring Harbor Laboratory, New York University Langone Medical Center, Oregon Health and Science University, and The European Bioinformatics Institute. Reactome data and software are distributed under the terms of the Creative Commons Attribution 4.0 License. A full description of the new and updated content is available on the Reactome website.

Follow us on Twitter: @reactome to get frequent updates about new and updated pathways, feature updates, and more!

Interaction

The Reactome team has released new versions of our protein-protein interaction files derived from reactions and complexes. These files were updated following user feedback, with the goal of providing extra annotation features through support from the PSI-MITAB 2.7 data format. Interactions are computationally generated based on the data stored on complexes and reactions. The interactions provided by Reactome are not curated and are not experimental data. In addition, the complexes and reactions in species other than human are derived by orthology inference from the corresponding human complexes and reactions. Tab-delimited formatted files are also provided for human and all species.

The four new files are:

Documentation about these files is available from the Data Download page.

The former versions of the protein-protein interaction files are still available but will be removed from service as of Version 62 in September 2017. We encourage users that programmatically access these files to update the scripts.

About the Reactome Project. Reactome is a collaboration between groups at the Ontario Institute for Cancer Research, Cold Spring Harbor Laboratory, New York University Langone Medical Center, Oregon Health and Science University, and The European Bioinformatics Institute. Reactome data and software are distributed under the terms of the Creative Commons Attribution 4.0 License. A full description of the new and updated content is available on the Reactome website.

Follow us on Twitter: @reactome to get frequent updates about new and updated pathways, feature updates, and more!

For more information. Please contact our This email address is being protected from spambots. You need JavaScript enabled to view it..

R-HSA-913531

New and Updated Pathways. In version V61, topics with new or revised pathways include: Gene expression (Transcriptional regulation by RUNX1), Immune System (Interleukin-12 family signaling), Signal Transduction (PTEN Regulation), and Transport of small molecules (Intracellular oxygen transport).

Thanks to our Contributors. Arkaitz Carracedo and Leonardo Salmena were our external authors. Sabine BaillyThorsten BurmesterLinda Shyue Huey ChuangYoshiaki ItoNisha KriplaniNick Leslie, and Esther van de Vosse were our external reviewers.

Annotation Statistics. Reactome comprises 11,042 human reactions organized into 2,148 pathways involving 10,940 proteins encoded by 10,691 different human genes, 1,763 small molecules, and 11,041 complexes. These annotations are supported by 26,859 literature references. We have projected these reactions onto 120,804 orthologous proteins, creating 20,780 orthologous pathways in 18 non-human species. Version 61 has annotations for 1,334 protein variants (mutated proteins) and their post-translationally modified forms, derived from 285 proteins. These have been used to annotate 506 disease-specific complexes and 906 disease-specific reactions organized into 453 pathways and subpathways, and tagged with 294 Disease Ontology terms.

About the Reactome Project. Reactome is a collaboration between groups at the Ontario Institute for Cancer Research, Oregon Health and Science University, New York University Langone Medical Center, and The European Bioinformatics Institute. Reactome data and software are distributed under the terms of the Creative Commons Attribution 4.0 License. A full description of the new and updated content is available on the Reactome website.

Follow us on Twitter: @reactome to get frequent updates about new and updated pathways, feature updates, and more!

For more information. Please contact our This email address is being protected from spambots. You need JavaScript enabled to view it..

New and Updated Pathways. In version V60, topics with new or revised pathways include: Cell cycle (Cyclin D associated events in G1), Cell-cell communication (SDK interactions), Cellular response to external stimuli (HSP90 chaperone cycle for steroid hormone receptors (SHR)), Disease (Diseases of Mismatch Repair), Gene Expression (TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest and Transcriptional Regulation by the CBFB:RUNX3 complex), Immune System (Butyrophilins and Regulation of complement cascade), Metabolism (Synthesis of IP2, IP, and Ins in the cytosolSynthesis of PIPs at the early endosome membraneSynthesis of PIPs at the ER membraneSynthesis of PIPs at the late endosome membrane, and Synthesis of PIPs at the plasma membrane), Metabolism of proteins (CREB3 factors activate genesNeddylationProtein ubiquitination, and SUMOylation of chromatin organizing proteins), Mitophagy (Receptor Mediated Mitophagy), Neuronal System (Receptor protein tyrosine phosphatases interactions), Organelle biogenesis and maintenance (Cristae formation), and Transport of small molecules (Mitochondrial calcium ion transport).

Thanks to our Contributors.  Wei-Chih Yang and Jian Lu are our external  authors. Joseph AinscoughSanjeevani  AroraJorge E Azevedo,  Jeehyeon BaeLucia BanciGautam BhaveDavid R BrownRoberta BullaAlexandre M CarmoLinda Shyue Huey ChuangKarlene A CimprichLaura CrisponiAlain de Bruin, Luisa Di Stefano , Ilaria DragoPablo C EcheverriaDu FengEmer S FerroDianne FordFrances V Fuller-PaceCem GabayDominique GagliardiMarcia  HaigisJ Wade HarperBarry HonigYoshiaki Ito, Veerle JanssensNathalie JossoJaewon  Ko , Vera Kozjak-PavlovicAnastasia KralliPaul J LehnerDominique  LeprinceBruce D LevyWei LiFrancisco LozanoJian LuMichael J Matunis, Birgit MeldalViolaine MoreauKyungjae MyungJoseph H NealeChristian Obinger,  R Jeroen PasterkampRichard PhippsDidier PicardElah PickDavid A RhodesPier e P Roger, Mark G Rush, Joshua R SanesMartin SchröderPierre ThibaultDick J H van den Boomen , Thomas E Van DykeRoberto M VanacoreNobutaka WakamiyaQinglu Wang, Bart Westendorp, Sandra E WileyMiriam WittmannGuilherme XavierWei-Chih YangAli A Zarrin, and Bing Zhu are our external reviewers.

Annotation Statistics. Reactome comprises 10,754 human reactions organized into 2,132 pathways involving 10,907 proteins encoded by 10,658 different human genes, 1,763 small molecules, and 10,748 complexes. These annotations are supported by 26,384 literature references. We have projected these reactions onto 115,881 orthologous proteins, creating 20,701 orthologous pathways in 18 non-human species. Version 60 has annotations for 1,503 protein variants (mutated proteins) and their post-translationally modified forms, derived from 285 proteins. These have been used to annotate 506 disease-specific complexes and 906 disease-specific reactions organized into 453 pathways and subpathways, and tagged with 294 Disease Ontology terms.

About the Reactome Project. Reactome is a collaboration between groups at the Ontario Institute for Cancer Research, Oregon Health and Science University, New York University Langone Medical Center, and The European Bioinformatics Institute. Reactome data and software are distributed under the terms of the Creative Commons Attribution 4.0 License. A full description of the new and updated content is available on the Reactome website.

Follow us on Twitter: @reactome to get frequent updates about new and updated pathways, feature updates, and more!

For more information. Please contact our This email address is being protected from spambots. You need JavaScript enabled to view it..

A new Reactome paper titled “Reactome pathway analysis: a high-performance in-memory approach” has been published in BMC Bioinformatics. More publications from the Reactome Team can be found here.

A new Reactome paper titled “Functional Interaction Network Construction and Analysis for Disease Discovery” has been published in Methods in Molecular Biology. More publications from the Reactome Team can be found here.

New and Updated Pathways. In version V59, topics with new or revised pathways include: Disease (Listeria monocytogenes entry into host cells), Hemostasis (Cell surface interaction at the vascular wall), Immune System (ButyrophilinsInterleukin 10 signalling, and Interleukin-4 and 13 signaling), Metabolism (Nicotinate metabolismSynthesis of PIPs at the nuclear envelopeVitamin B5 (pantothenate) metabolism, and Aryl hydrocarbon receptor signalling), Metabolism of proteins (E3 ubiquitin ligases ubiquitinate target proteinsPeptide-ligand binding receptorsProtein methylationRAB geranylgeranylation), Signal transduction (Class A/1 (Rhodopsin-like receptors), and Vesicle-mediated transport (TBC RABGAPs).

Thanks to our Contributors. Our external reviewers are Jorge AzevedoEster BoixLu DengPål FalnesVardan KaramyanSamuel LeibovichWeei-Chin LinCharuta PalsuledesaiJoel PomerantzWalter ReithSylvie Ricard-BlumChristian SchwerkBruce Spiegelman, and Xiaochun Yu.

Annotation Statistics. Reactome comprises 10,391 human reactions organized into 2,080 pathways involving 10,624 proteins encoded by 10,381 different human genes, and 1,735 small molecules. These annotations are supported by 25,449 literature references. We have projected these reactions onto 115,881 orthologous proteins, creating 20,164 orthologous pathways in 18 non-human species. Version 59 has annotations for 1,496 protein variants (mutated proteins) and their post-translationally modified forms, derived from 285 proteins. These have been used to annotate 506 disease-specific complexes and 897 disease-specific reactions organized into 447 pathways and subpathways, and tagged with 294 Disease Ontology terms.

About the Reactome Project. Reactome is a collaboration between groups at the Ontario Institute for Cancer Research, New York University Medical Center, and The European Bioinformatics Institute. Reactome data and software are distributed under the terms of the Creative Commons Attribution 4.0 License. A full description of the new and updated content is available on the Reactome website.

Follow us on Twitter: @reactome to get frequent updates about new and updated pathways, feature updates, and more!

For more information. Please contact our This email address is being protected from spambots. You need JavaScript enabled to view it..

10K Reactome

The Reactome team is pleased to announce that it met a major milestone in October 2016 with the annotation and release of its 10,000th human protein. Reactome (www.reactome.org) is an open access curated knowledgebase which relates human genes, proteins and other biomolecules to the biological pathways and processes in which they participate. It is a key resource for the biomedical research community, and is widely used by researchers around the world to interpret high-throughput experiments in genetics, genomics and proteomics. Given that the human genome contains roughly 20,000 protein-coding genes in total, the annotation of the 10,000th protein means that Reactome now covers half of the protein-coding portion of the genome. This makes Reactome the most comprehensive open access pathway knowledgebase available to the scientific community.

By relating genes and proteins to normal and abnormal biological pathways, Reactome allows researchers to identify patterns in large data sets. For example, researchers can use Reactome to reduce an experiment that identified thousands of genes whose activities are altered in a disease to a manageable number of key biological pathways that are disrupted by these changes. Researchers can then combine Reactome with other databases to find drugs and protein targets that might reverse the pathway alterations, or to devise ways of diagnosing the disease at an early stage. Via its web site, online tools, and specialized visualization and analysis applications, Reactome has been incorporated into more than 400 third-party genome analysis tools, and has been cited more than 4,000 times in the scientific literature. 

Reactome has been in continuous operation since 2004 and is an international collaboration among the Ontario Institute for Cancer Research in Canada, New York University School of Medicine in the United States, and the European Bioinformatics Institute in the United Kingdom. It is staffed by expert biological curators, bioinformaticians and computer scientists. Much of its content is provided by community authors and peer reviewers who are assisted by the curatorial staff. The Reactome content, including pathway data and the software infrastructure, are available to all comers free of charge under a Creative Commons open access license. Reactome is supported by grants from the US National Institutes of Health, the Ontario Research Fund, the University of Toronto, OpenTargets, Genome Canada, and the European Molecular Biology Laboratory.

Follow us on Twitter: @reactome to get frequent updates about new and updated pathways, feature updates, and more!

For more information please contact our This email address is being protected from spambots. You need JavaScript enabled to view it..

illustration deregulated CDK5 triggers multiple neurodegenerative pathways 72

New and Updated Pathways. With version V58, Reactome has annotations for over 10,000 human proteins. New or revised pathways include: Cell cycle (FBXL7 down-regulates AURKA during mitotic entry and in early mitosis), Developmental biology (Keratinization), Disease (Oncogenic MAPK signaling and Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer’s disease models), Gene expression (PI5P Regulates TP53 AcetylationTranscriptional regulation by the AP-2 (TFAP2) family of transcription factors),  Immune system  (Neutrophil degranulation and Antimicrobial peptides), Metabolism of proteins (Synthesis of active ubiquitin: roles of E1 and E2 enzymes), Signal transduction (Signaling by MET and Downregulation of ERBB2 signaling), and Vesicle-mediated transport (RAB GEFs exchange GTP for GDP on RABs).

A pathway illustration is available for Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer’s disease .

Thanks to our Contributors. Our external author is Kavita Shah.  Emily AyoubJorge AzevedoWalter BirchmeierMiroslav BlumenbergMaria BogachekNullin DivechaRoman DziarskiRhys GrantDavid HainsNiels HeegardGuustaaf HeynenCatherine LindonAndrea MaratRobert StephensMichel Tremblay, and Ronald Weigel are our external reviewers.

Reactome comprises 10,168 human reactions organized into 2,069 pathways involving 10,461 proteins encoded by 10,221 different human genes, and 1,710 small molecules. These annotations are supported by 24,974 literature references. We have projected these reactions onto 110,710 orthologous proteins, creating 19,991 orthologous pathways in 18 non-human species.

Reactome is a collaboration between groups at the Ontario Institute for Cancer Research, New York University Medical Center, and The European Bioinformatics Institute. Reactome data and software are distributed under the terms of the Creative Commons Attribution 4.0 License. A full description of the new and updated content is available on the Reactome website.

Follow us on Twitter: @reactome to get frequent updates about new and updated pathways, feature updates, and more!

For more information please contact our This email address is being protected from spambots. You need JavaScript enabled to view it..

In version V57, topics with new or revised pathways include: Developmental biology (RET signaling), Disease (Signaling by FGFR in disease and Defective CFTR causes cystic fibrosis), Gene expression (rRNA modification in the mitochondrion and Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors), Immune system (ER-Phagosome pathwayInterleukin-7 signalingRegulation by endogenous TLR ligand, and TCR signaling), Metabolism (Lipid digestion, mobilization, and transport and Phosphate bond hydrolysis by NTPDase proteins). Metabolism of proteins (Deubiquitination), Neuronal system (Interactions of neurexins and neuroligins at synapses and SALM protein interactions at synapse). Signal transduction (EGFR downregulationSignaling by FGFR1, and FGFRL1 modulation of FGFR1 signaling), Transmembrane transport of small molecules (ABC-family proteins mediated transport) and Vesicle-mediated transport (Clathrin-mediated endocytosis).

Our external author is Alba SanchisCostin AntonescuJohn Bergeron, Daniel BogenhagenNunzio BottiniGuang-Chao ChenIgor DawidRegina FluhrerNoriko GotohFrancesca GranucciRichard GrosePaul HeppenstallJing HuJan HuertasWenqin LuoMalay MandalBirgit MeldalDaniel MoralesTatsunori NishimuraRonald PetraliaGail SeaboldSunny SharmaStephanie StanfordJean SévignyPhilip WashbourneIvan Zanoni, and Valeria Zarelli are our external reviewers.