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      Ensembl 2021

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      Nucleic Acids Research
      Oxford University Press

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          Abstract

          The Ensembl project ( https://www.ensembl.org) annotates genomes and disseminates genomic data for vertebrate species. We create detailed and comprehensive annotation of gene structures, regulatory elements and variants, and enable comparative genomics by inferring the evolutionary history of genes and genomes. Our integrated genomic data are made available in a variety of ways, including genome browsers, search interfaces, specialist tools such as the Ensembl Variant Effect Predictor, download files and programmatic interfaces. Here, we present recent Ensembl developments including two new website portals. Ensembl Rapid Release ( http://rapid.ensembl.org) is designed to provide core tools and services for genomes as soon as possible and has been deployed to support large biodiversity sequencing projects. Our SARS-CoV-2 genome browser ( https://covid-19.ensembl.org) integrates our own annotation with publicly available genomic data from numerous sources to facilitate the use of genomics in the international scientific response to the COVID-19 pandemic. We also report on other updates to our annotation resources, tools and services. All Ensembl data and software are freely available without restriction.

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          A new coronavirus associated with human respiratory disease in China

          Emerging infectious diseases, such as severe acute respiratory syndrome (SARS) and Zika virus disease, present a major threat to public health 1–3 . Despite intense research efforts, how, when and where new diseases appear are still a source of considerable uncertainty. A severe respiratory disease was recently reported in Wuhan, Hubei province, China. As of 25 January 2020, at least 1,975 cases had been reported since the first patient was hospitalized on 12 December 2019. Epidemiological investigations have suggested that the outbreak was associated with a seafood market in Wuhan. Here we study a single patient who was a worker at the market and who was admitted to the Central Hospital of Wuhan on 26 December 2019 while experiencing a severe respiratory syndrome that included fever, dizziness and a cough. Metagenomic RNA sequencing 4 of a sample of bronchoalveolar lavage fluid from the patient identified a new RNA virus strain from the family Coronaviridae, which is designated here ‘WH-Human 1’ coronavirus (and has also been referred to as ‘2019-nCoV’). Phylogenetic analysis of the complete viral genome (29,903 nucleotides) revealed that the virus was most closely related (89.1% nucleotide similarity) to a group of SARS-like coronaviruses (genus Betacoronavirus, subgenus Sarbecovirus) that had previously been found in bats in China 5 . This outbreak highlights the ongoing ability of viral spill-over from animals to cause severe disease in humans.
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            The mutational constraint spectrum quantified from variation in 141,456 humans

            Genetic variants that inactivate protein-coding genes are a powerful source of information about the phenotypic consequences of gene disruption: genes that are crucial for the function of an organism will be depleted of such variants in natural populations, whereas non-essential genes will tolerate their accumulation. However, predicted loss-of-function variants are enriched for annotation errors, and tend to be found at extremely low frequencies, so their analysis requires careful variant annotation and very large sample sizes 1 . Here we describe the aggregation of 125,748 exomes and 15,708 genomes from human sequencing studies into the Genome Aggregation Database (gnomAD). We identify 443,769 high-confidence predicted loss-of-function variants in this cohort after filtering for artefacts caused by sequencing and annotation errors. Using an improved model of human mutation rates, we classify human protein-coding genes along a spectrum that represents tolerance to inactivation, validate this classification using data from model organisms and engineered human cells, and show that it can be used to improve the power of gene discovery for both common and rare diseases.
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              An Integrated Encyclopedia of DNA Elements in the Human Genome

              Summary The human genome encodes the blueprint of life, but the function of the vast majority of its nearly three billion bases is unknown. The Encyclopedia of DNA Elements (ENCODE) project has systematically mapped regions of transcription, transcription factor association, chromatin structure, and histone modification. These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well-studied protein-coding regions. Many discovered candidate regulatory elements are physically associated with one another and with expressed genes, providing new insights into the mechanisms of gene regulation. The newly identified elements also show a statistical correspondence to sequence variants linked to human disease, and can thereby guide interpretation of this variation. Overall the project provides new insights into the organization and regulation of our genes and genome, and an expansive resource of functional annotations for biomedical research.
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                Author and article information

                Contributors
                Journal
                Nucleic Acids Res
                Nucleic Acids Res
                nar
                Nucleic Acids Research
                Oxford University Press
                0305-1048
                1362-4962
                08 January 2021
                02 November 2020
                02 November 2020
                : 49
                : D1
                : D884-D891
                Affiliations
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton , Cambridge CB10 1SD, UK
                Author notes
                To whom correspondence should be addressed. Tel: +44 1223 492 581; Fax: +44 1223 494 468; Email: flicek@ 123456ebi.ac.uk
                Author information
                http://orcid.org/0000-0002-1751-9226
                http://orcid.org/0000-0002-4333-628X
                http://orcid.org/0000-0002-7669-2934
                http://orcid.org/0000-0002-8886-4772
                http://orcid.org/0000-0002-3897-7955
                Article
                gkaa942
                10.1093/nar/gkaa942
                7778975
                33137190
                8b278170-ad52-439c-aed8-76dc691c41f4
                © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 07 October 2020
                : 05 October 2020
                : 22 September 2020
                Page count
                Pages: 8
                Funding
                Funded by: Wellcome Trust, DOI 10.13039/100010269;
                Award ID: WT108749/Z/15/Z
                Award ID: WT104947/Z/14/Z
                Award ID: WT200990/Z/16/Z
                Award ID: WT201535/Z/16/Z
                Award ID: WT212925/Z/18/Z
                Award ID: WT218328/B/19/Z
                Funded by: National Human Genome Research Institute, DOI 10.13039/100000051;
                Award ID: U41HG007823
                Award ID: 2U41HG007234
                Award ID: U41HG010972
                Award ID: 2U24HG007497–05
                Funded by: Biotechnology and Biological Sciences Research Council, DOI 10.13039/501100000268;
                Award ID: BB/N019563/1
                Award ID: BB/M011615/1
                Award ID: BB/S020152/1
                Award ID: BB/P016855/1
                Award ID: BB/S02011X/1
                Award ID: BB/P024602/1
                Funded by: British Council, DOI 10.13039/501100000308;
                Award ID: 414710385
                Funded by: Horizon 2020, DOI 10.13039/100010661;
                Award ID: 733161
                Award ID: 825575
                Award ID: 817923
                Award ID: 817998
                Award ID: 815668
                Categories
                AcademicSubjects/SCI00010
                Database Issue

                Genetics
                Genetics

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