New and Updated Topics and Pathways. In V81, Topics with new or revised pathways include Development (Germ layer formation at gastrulation), Immune system (TAK1-dependent IKK and NF-kB activation), and Signal Transduction (Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer). The SARS-CoV-2 life cycle has been updated to reflect our growing understanding of the life cycle. Viral events have partitioned into early and late subpathways. Early events begin with viral entry and carry through to initial gene expression; late events include the massive organelle reorganizations and viral release as host cells transition to viral shedding factories. SARS-CoV-2 annotation now includes 224 events; with this release 61 of those events have been updated with experimental support from the body of COVID-19 literature that has emerged since March 2020. Additionally, in collaboration with Rachel Huddart with PharmGKB, we have added 101 drug interactions associated with 63 pathways in this release bringing the total number of drugs represented in Reactome to 1022.

New and Updated Illustrations. Developmental BiologyGastrulationNucleotide catabolism defects, and Nucleotide salvage defects have a new or revised Illustration with embedded navigation Features.

Thanks to our Contributors. Osvaldo ContrerasRainer de MartinRachel HuddartNaz Salehin, and Patrick P L Tam are our external reviewers.

Annotation Statistics. Reactome comprises 14,246 human reactions organized into 2,585 pathways involving 11,291 proteins and modified forms of proteins encoded by 11,088 different human genes, 13,984 complexes, 1,986 small molecules, and 1,022 drugs. These annotations are supported by 35,629 literature references. We have projected these reactions onto 83,266 orthologous proteins, creating 19,328 orthologous pathways in 15 non-human species. Version 81 has annotations for 5,422 protein variants (mutated proteins) and their post-translationally modified forms, derived from 352 proteins, which have been used to annotate disease-specific 1,609 reactions and 697 pathways.

Tools and Data. Our services and software tools are designed for biologists, bioinformaticians, and software developers. Pathway data is available to view in our Pathway Browser, to analyze your own dataset, to download, and access programmatically through our Content and Analysis Services. The ReactomeFIViz app and ReactomeGSA package provides tools for multi-omics data analysis. The Web Portal provides a collection of web-based tools to help researchers place understudied proteins in a pathway context. 

Documentation and Training. Visit our online User Guide to access documentation supporting pathway analysis of experimental data. The Developer's Zone provides detailed documentation regarding our software, tools, and web services. Training and learning materials can be found here.

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 EMBL - European Bioinformatics Institute. Reactome is an ELIXIR Core Data Resource. 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 applies 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: If you have a question, want to provide feedback, or are interested in collaborating with us to annotate a topic, please contact us at This email address is being protected from spambots. You need JavaScript enabled to view it..

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