New Feature. In response to the COVID-19 pandemic, Reactome is fast-tracking the annotation of Human Coronavirus infection pathways in collaboration with the COVID-19 Disease Map group. Reactome release 74 features the SARS-CoV-2 (COVID-19) infection pathway. To generate this pathway, we started with a rough draft generated computationally via our orthoinference process from the previously manually curated, peer-reviewed Reactome SARS-CoV-1 (Human SARS coronavirus) infection pathway. The draft SARS-CoV-2 (COVID-19) infection pathway events and entities were then reviewed by Reactome curators and curated using published SARS-CoV-2 experimental data. Before finalization, the resulting curated SARS-CoV-2 infection pathway was peer-reviewed by external experts. The current pathway consists of 101 reactions involving 489 molecular entities (279 proteins, 12 RNAs and 198 other), and is supported by citations to 227 publications. In future releases of Reactome, we will extend our annotation of the pathway, indicate drugs and other compounds that modulate steps in infection, and add molecular events that link infectious pathway steps to host immune processes and other aspects of human biology that determine responses to viral infection. This accelerated annotation project is supported by a recently-received supplement  grant U41 HG003751-13S1 from the National Human Genome Research Institute.

New and Updated Pathways. Other topics with new or revised pathways in release 74 include Disease (Defective RIPK1-mediated regulated necrosis) and Programmed cell death (RIPK1-mediated regulated necrosis).

New and Updated Illustrations. Illustrations with embedded navigation features have been added or revised for Diseases of metabolism, SARS-CoV infections, ABC transporter disorders, Diseases associated with surfactant metabolism, Diseases of cellular response to stress, Diseases of DNA repair, Diseases of mitotic cell cycle, Diseases of neuronal system, Diseases of signal transduction by growth factor receptors and second messengers, Disorders of developmental biology, Disorders of transmembrane transporters, Signaling by TGF-beta receptor complex in cancer, and SLC transporter disorders. New static illustrations are now available for Complement cascade, Rho GTPase cycle, SARS-CoV-2 infection, and Toll-Like receptors cascades.

Thanks to our Contributors. Our external author is Andrea Senff-Ribeiro and our external reviewers are Marcio Luis Acencio, Najoua Lalaoui, James M Murphy.

Annotation Statistics. Reactome comprises 13,416 human reactions organized into 2,441 pathways involving 11,110 proteins and modified forms of proteins encoded by 10,922 different human genes, 12,976 complexes, 1,854 small molecules, and 428 drugs. These annotations are supported by 32,297 literature references. We have projected these reactions onto 79,190 orthologous proteins, creating 18,462 orthologous pathways in 15 non-human species. Version 74 has annotations for 2,624 protein variants (mutated proteins) and their post-translationally modified forms, derived from 328 proteins, which have been used to annotate disease-specificreactions and 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 to access programmatically through our Content and Analysis Services. The ReactomeFIViz app for Cytoscape provides tools to find pathways and network patterns related to cancer and other types of diseases.

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 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!

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