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      Integration of the Drug–Gene Interaction Database (DGIdb 4.0) with open crowdsource efforts

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          Abstract

          The Drug-Gene Interaction Database (DGIdb, www.dgidb.org) is a web resource that provides information on drug-gene interactions and druggable genes from publications, databases, and other web-based sources. Drug, gene, and interaction data are normalized and merged into conceptual groups. The information contained in this resource is available to users through a straightforward search interface, an application programming interface (API), and TSV data downloads. DGIdb 4.0 is the latest major version release of this database. A primary focus of this update was integration with crowdsourced efforts, leveraging the Drug Target Commons for community-contributed interaction data, Wikidata to facilitate term normalization, and export to NDEx for drug-gene interaction network representations. Seven new sources have been added since the last major version release, bringing the total number of sources included to 41. Of the previously aggregated sources, 15 have been updated. DGIdb 4.0 also includes improvements to the process of drug normalization and grouping of imported sources. Other notable updates include the introduction of a more sophisticated Query Score for interaction search results, an updated Interaction Score, the inclusion of interaction directionality, and several additional improvements to search features, data releases, licensing documentation and the application framework.

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          Most cited references31

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          Gene Ontology: tool for the unification of biology

          Genomic sequencing has made it clear that a large fraction of the genes specifying the core biological functions are shared by all eukaryotes. Knowledge of the biological role of such shared proteins in one organism can often be transferred to other organisms. The goal of the Gene Ontology Consortium is to produce a dynamic, controlled vocabulary that can be applied to all eukaryotes even as knowledge of gene and protein roles in cells is accumulating and changing. To this end, three independent ontologies accessible on the World-Wide Web (http://www.geneontology.org) are being constructed: biological process, molecular function and cellular component.
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            DrugBank 5.0: a major update to the DrugBank database for 2018

            Abstract DrugBank (www.drugbank.ca) is a web-enabled database containing comprehensive molecular information about drugs, their mechanisms, their interactions and their targets. First described in 2006, DrugBank has continued to evolve over the past 12 years in response to marked improvements to web standards and changing needs for drug research and development. This year’s update, DrugBank 5.0, represents the most significant upgrade to the database in more than 10 years. In many cases, existing data content has grown by 100% or more over the last update. For instance, the total number of investigational drugs in the database has grown by almost 300%, the number of drug-drug interactions has grown by nearly 600% and the number of SNP-associated drug effects has grown more than 3000%. Significant improvements have been made to the quantity, quality and consistency of drug indications, drug binding data as well as drug-drug and drug-food interactions. A great deal of brand new data have also been added to DrugBank 5.0. This includes information on the influence of hundreds of drugs on metabolite levels (pharmacometabolomics), gene expression levels (pharmacotranscriptomics) and protein expression levels (pharmacoprotoemics). New data have also been added on the status of hundreds of new drug clinical trials and existing drug repurposing trials. Many other important improvements in the content, interface and performance of the DrugBank website have been made and these should greatly enhance its ease of use, utility and potential applications in many areas of pharmacological research, pharmaceutical science and drug education.
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              COSMIC: the Catalogue Of Somatic Mutations In Cancer

              Abstract COSMIC, the Catalogue Of Somatic Mutations In Cancer (https://cancer.sanger.ac.uk) is the most detailed and comprehensive resource for exploring the effect of somatic mutations in human cancer. The latest release, COSMIC v86 (August 2018), includes almost 6 million coding mutations across 1.4 million tumour samples, curated from over 26 000 publications. In addition to coding mutations, COSMIC covers all the genetic mechanisms by which somatic mutations promote cancer, including non-coding mutations, gene fusions, copy-number variants and drug-resistance mutations. COSMIC is primarily hand-curated, ensuring quality, accuracy and descriptive data capture. Building on our manual curation processes, we are introducing new initiatives that allow us to prioritize key genes and diseases, and to react more quickly and comprehensively to new findings in the literature. Alongside improvements to the public website and data-download systems, new functionality in COSMIC-3D allows exploration of mutations within three-dimensional protein structures, their protein structural and functional impacts, and implications for druggability. In parallel with COSMIC’s deep and broad variant coverage, the Cancer Gene Census (CGC) describes a curated catalogue of genes driving every form of human cancer. Currently describing 719 genes, the CGC has recently introduced functional descriptions of how each gene drives disease, summarized into the 10 cancer Hallmarks.
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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
                25 November 2020
                25 November 2020
                : 49
                : D1
                : D1144-D1151
                Affiliations
                Department of Medicine, Division of Oncology, Washington University School of Medicine , St Louis, MO 63110, USA
                McDonnell Genome Institute, Washington University School of Medicine , St Louis, MO 63108, USA
                McDonnell Genome Institute, Washington University School of Medicine , St Louis, MO 63108, USA
                Department of Medicine, Division of Oncology, Washington University School of Medicine , St Louis, MO 63110, USA
                McDonnell Genome Institute, Washington University School of Medicine , St Louis, MO 63108, USA
                McDonnell Genome Institute, Washington University School of Medicine , St Louis, MO 63108, USA
                McDonnell Genome Institute, Washington University School of Medicine , St Louis, MO 63108, USA
                Department of Medicine, Division of Oncology, Washington University School of Medicine , St Louis, MO 63110, USA
                McDonnell Genome Institute, Washington University School of Medicine , St Louis, MO 63108, USA
                Department of Medicine, Division of Oncology, Washington University School of Medicine , St Louis, MO 63110, USA
                McDonnell Genome Institute, Washington University School of Medicine , St Louis, MO 63108, USA
                Department of Genetics, Washington University School of Medicine , St Louis, MO 63110, USA
                Siteman Cancer Center, Washington University School of Medicine , St Louis, MO 63110, USA
                Department of Medicine, Division of Oncology, Washington University School of Medicine , St Louis, MO 63110, USA
                McDonnell Genome Institute, Washington University School of Medicine , St Louis, MO 63108, USA
                Department of Genetics, Washington University School of Medicine , St Louis, MO 63110, USA
                Siteman Cancer Center, Washington University School of Medicine , St Louis, MO 63110, USA
                Department of Medicine, Division of Oncology, Washington University School of Medicine , St Louis, MO 63110, USA
                McDonnell Genome Institute, Washington University School of Medicine , St Louis, MO 63108, USA
                The Steve and Cindy Rasmussen Institute for Genomic Medicine, Nationwide Children's Hospital , Columbus, OH 43215, USA
                Department of Pediatrics, The Ohio State University College of Medicine , Columbus, OH 43210, USA
                Author notes
                To whom correspondence should be addressed. Tel: +1 614 355 1645; Fax: +1 614 355 6833; Email: Alex.Wagner@ 123456nationwidechildrens.org
                Correspondence may also be addressed to Obi L. Griffith. Tel: +1 314 747 9248; Fax: +1 314 286 1810; Email: obigriffith@ 123456wustl.edu
                Correspondence may also be addressed to Malachi Griffith. Tel: +1 314 286 1274; Fax: +1 314 286 1810; Email: mgriffit@ 123456wustl.edu

                The authors wish it to be known that, in their opinion, the first three authors should be regarded as joint First Authors.

                Author information
                http://orcid.org/0000-0001-6978-3515
                http://orcid.org/0000-0003-4378-7328
                http://orcid.org/0000-0003-0890-6889
                http://orcid.org/0000-0003-0944-3126
                http://orcid.org/0000-0002-0197-2245
                http://orcid.org/0000-0002-4349-2442
                http://orcid.org/0000-0002-6388-446X
                http://orcid.org/0000-0002-0843-4271
                http://orcid.org/0000-0002-2502-8961
                Article
                gkaa1084
                10.1093/nar/gkaa1084
                7778926
                33237278
                803c8914-f608-4681-a366-57cdb2778122
                © 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
                : 23 October 2020
                : 21 October 2020
                : 15 September 2020
                Page count
                Pages: 8
                Funding
                Funded by: National Human Genome Research Institute, DOI 10.13039/100000051;
                Award ID: K99HG010157
                Award ID: R00HG007940
                Funded by: National Cancer Institute, DOI 10.13039/100000054;
                Award ID: U01CA209936
                Award ID: U01CA248235
                Award ID: U24CA237719
                Categories
                AcademicSubjects/SCI00010
                Database Issue

                Genetics
                Genetics

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