We describe how UniProtKB responded to the COVID-19 pandemic through expert curation of relevant entries that were rapidly made available to the research community through a dedicated portal. the contents by NLM or the National Institutes of Health. We have adopted new methods of assessing proteome completeness and quality. Your comment will be reviewed and published at the journal's discretion. Clinically relevant sources of variation (e.g. We have adopted the MMseqs2 algorithm to improve the speed of UniRef production (11), decreasing the time taken to perform UniRef50 clustering from four weeks to 60 hours, and improved procedures to compute proteome clusters and identify representative proteomes, pan proteomes, and core and accessory proteomes. For example, UniProt accepts primary sequences derived from peptide sequencing experiments. The aim of the UniProt Knowledgebase is to provide users with a comprehensive, high-quality and freely accessible set of protein sequences annotated with functional information. Findings from Novel Insomnia Treatment Experiment ("NITE"), a randomised controlled trial. In this article, we describe significant updates that we have made over the last two years to the resource. It contains a large amount of information about the biological function of proteins derived from the research literature. Funding for open access charge: National Institutes of Health [U24HG007822]. This enables us to leverage the scientific community as a resource for enhancing our curated content, emulating a model already adopted by a number of model organism databases, such as WormBase (40), PomBase (41) and FlyBase (42). Garcia L., Bolleman J., Gehant S., Redaschi N., Martin M., Consortium UniProt. (B) The interaction viewer reusable web component in the Nightingale library. Bolt B.J., Rodgers F.H., Shafie M., Kersey P.J., Berriman M., Howe K.L. UniRef protein sequence clusters facilitate sequence similarity searches, functional annotation, gene prediction, and genome and proteome comparisons. Attribution 4.0 International (CC BY 4.0) license, except where further licensing details are provided. Understanding the value of secondary research data UniProt Knowledgebase: a hub of integrated protein data The ProtVista viewer has already been implemented by the Open Targets (43) and the Pharos (44) databases of unstudied and understudied drug targets amongst others. Arnaboldi V., Raciti D., VanAuken K., Chan J.N., Mller H.-M., Sternberg P.W.. . UniProt proteomes provide the set of proteins currently believed to be expressed by an organism. All materials are free cultural works licensed under a Creative Commons The https:// ensures that you are connecting to the The international nucleotide sequence database collaboration. The automatic annotation systems described above require the presence of an ordered region of protein that can be recognized as a domain or provide a signature of family membership which has been identified by an InterPro member database. Currently at least 95% of human genes are believed to be alternatively spliced (20,21) resulting in an estimated 75 000 distinct protein coding sequences. The UniProt Knowledgebase (UniProtKB) acts as a central hub of protein knowledge by providing a unified view of protein sequence and functional information. In our last update published in this journal in 2019 (3), we described how we are responding to the growth in microbial protein sequence records, largely derived from high-quality metagenomic assembled genomes. (A) The UniProtKB interaction viewer as seen in entry UniProtKB:{"type":"entrez-protein","attrs":{"text":"Q9NSA3","term_id":"29428025","term_text":"Q9NSA3"}}Q9NSA3, the beta-catenin-interacting protein 1. UniProt users have always actively engaged with us and provide important feedback to the resource. European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Genome Campus, Hinxton CB10 1SD, UK. This, in turn, has allowed us to further improve our mapping of imported data, for example binary protein interactions imported from the IMEx Consortium of molecular interaction databases are now displayed at the specific isoform/post-processed chain level. The UniProt databases exist to support biological and biomedical research by providing a complete compendium of all known protein sequence data linked to a summary of the experimentally verified, or computationally predicted, functional information about that protein. UniProt UniProt continues to play its pivotal role in the fields of biology and biomedicine, collecting, standardizing and organizing knowledge of proteins and their functions to create a reference framework for multiscale biomedical data integration and analysis. Submissions are minimally checked by an experienced curator before being added to the Publications section of the record. Please send your feedback and suggestions to the e-mail address help@uniprot.org or via the contact link on the UniProt website. including isoforms) that map to the genome. Watkins X., Garcia L.J., Pundir S., Martin M.J.UniProt Consortium. UniProt is a freely accessible database of protein sequence and functional information, many entries being derived from genome sequencing projects. Vallenet D., Calteau A., Dubois M., Amours P., Bazin A., Beuvin M., Burlot L., Bussell X., Fouteau S., Gautreau G. et al. This work is critical to many areas of science including biology, medicine and biotechnology and is generating a wealth of data. These unreviewed records are enriched with functional annotation by systems using the protein classification tool InterPro (24), which classifies sequences at superfamily, family and subfamily levels, and predicts the occurrence of functional domains and important sites. Wang E.T., Sandberg R., Luo S., Khrebtukova I., Zhang L., Mayr C., Kingsmore S.F., Schroth G.P., Burge C.B. Clinical significance is evaluated using the guidelines of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG-AMP) (17) and ClinGen tools such as the pathogenicity calculator (18), with all clinical interpretations routinely submitted to ClinVar to promote reuse (19). However, over 20% of unreviewed proteins in UniProt do not contain any InterPro signature regions, and many InterPro signatures are not associated with transferable annotation. The representation of isoform-specific annotations and sequence features has been enhanced in the website to facilitate the exploration of this information in UniProt (Figure (Figure44). We continue to increase the number of UniRules used for annotation and this set has now grown to 6768 (release 2020_04) rules in total. Bethesda, MD 20894, Web Policies The functional information extracted from the literature is added both in the form of human readable summaries and via structured vocabularies, such as the Gene Ontology (GO) (12). In addition to the increased use of structured vocabularies to enhance accessibility to UniProtKB records, we have also improved the presentation of the information within each entry. This replaces the previous rule-based SAAS system. In recognition of the quality of our data, and the service we provide, UniProt was recognised as an ELIXIR Core Data Resource in 2017 (1) and received the CoreTrustSeal certification in 2020. . We describe how UniProtKB responded to the COVID-19 pandemic through expert curation of relevant entries that were rapidly made available to the research community through a dedicated portal. PeptideAtlas (32), MassIVE (33) and jPOST (34)) and other large-scale initiatives (CPTAC (35), ProteomicsDB (36), MaxQB (37), ETD and CTDP (38)). Clinically relevant sources of variation (e.g. Submissions are minimally checked by an experienced curator before being added to the Publications section of the record. Data captured from the scientific literature includes information on protein and gene names, function, catalytic activity, cofactors, subcellular location, protein-protein interactions and much more. The largest part of missing annotation seems to derive from intrinsically disordered (ID) protein regions, therefore we have collaborated with the MobiDB-lite resource to provide a consensus-based prediction of long disorder (27). The COVID-19 disease portal is a prototype of our intention to provide disease-centric access points to the wealth of data contained in UniProtKB records. Developed by the Swiss-Prot . The number of sequences in UniProtKB has risen to approximately 190 million, despite continued work to reduce sequence redundancy at the proteome level. For downloading complete data sets we recommend using ftp.uniprot.org. The UniProt Knowledgebase (UniProtKB) combines reviewed UniProtKB/Swiss-Prot entries, to which data have been added by our expert biocuration team, with the unreviewed UniProtKB/TrEMBL entries that are annotated by automated systems. Enzyme annotation in UniProtKB using Rhea. Patel R.Y., Shah N., Jackson A.R., Ghosh R., Pawliczek P., Paithankar S., Baker A., Riehle K., Chen H., Milosavljevic S. et al ClinGen Pathogenicity Calculator: a configurable system for assessing pathogenicity of genetic variants. . The UniProt Consortium, UniProt: the universal protein knowledgebase in 2021, Nucleic Acids Research, Volume 49, Issue D1, 8 January 2021, Pages D480D489, https://doi.org/10.1093/nar/gkaa1100. Over 30 000 of these variants have been associated with Mendelian diseases. Garcia L., Bolleman J., Gehant S., Redaschi N., Martin M., Consortium UniProt, Karsch-Mizrachi I., Takagi T., Cochrane GInternational Nucleotide Sequence Database Collaboration. The ever-increasing amount of genomic data arising from current sequencing projects means that the proportion of unreviewed records in UniProtKB/TrEMBL describing largely predicted proteins represents by far the largest, and most rapidly growing, section of UniProtKB. You can navigate within the entry by clicking on the side-bar. . UniProt curators specializing in viral proteomes rapidly annotated the proteins encoded by this viral genome, first by similarity to other closely related coronaviruses, and subsequently by updating relevant entries with experimental data as soon as this was published. Inclusion in an NLM database does not imply endorsement of, or agreement with, Collectively, these have already resulted in the number of entries contained in UniProtKB growing by >65 million records, an increase of >50% in just 2 years. The UniProt Archive (UniParc) provides a stable, comprehensive sequence collection without redundant sequences by storing the complete body of publicly available protein sequence data. Additionally, in release 2020_04, more than 15 million uncharacterized protein names have been improved using InterPro member database signatures, updating their name to domain X containing protein following the International Protein Nomenclature Guidelines (https://www.uniprot.org/docs/International_Protein_Nomenclature_Guidelines.pdf). Its genome sequence was first made publicly available by the International Nucleotide Sequence Database Collaboration (INSDC) on 10 January 2020 (accession number {"type":"entrez-nucleotide","attrs":{"text":"MN908947","term_id":"1798172431","term_text":"MN908947"}}MN908947). Hybrid databases and families of databases. . Pan Q., Shai O., Lee L.J., Frey B.J., Blencowe B.J. Its genome sequence was first made publicly available by the International Nucleotide Sequence Database Collaboration (INSDC) on 10 January 2020 (accession number MN908947). . (i) Use Add a publication functionality (red box) in the UniProtKB entry. We follow a user-centered design process, conducting regular workshops, user testing, surveys and user research activities involving many users worldwide with varied research backgrounds and use cases. . It consists of: UniProtKB/Swiss-Prot (expert-curated records) and UniProtKB/TrEMBL (computationally annotated records). The semi-automated rule-based computational annotation UniRule system (25) annotates experimentally uncharacterized proteins based on similarity to known experimentally characterized proteins, adding properties, such as protein name, functional annotation, catalytic activity, pathway, GO terms and subcellular location. UniProt is produced by the UniProt Consortium, a collaboration between the European Bioinformatics Institute (EMBL-EBI), the SIB Swiss Institute of Bioinformatics and the Protein Information Resource (PIR). Continue on to the final pages of this online tutorial for recommendations on what to learn next and to tell us what you thought of this tutorial. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was identified as the cause of the 20192020 COVID-19 viral outbreak and ensuing pandemic. A user-friendly visualization for chemical reactions has also been developed to enable Rhea reactions to be viewed on the website within the appropriate UniProt entry (Figure (Figure3).3).