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      DEG 15, an update of the Database of Essential Genes that includes built-in analysis tools

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          Abstract

          Essential genes refer to genes that are required by an organism to survive under specific conditions. Studies of the minimal-gene-set for bacteria have elucidated fundamental cellular processes that sustain life. The past five years have seen a significant progress in identifying human essential genes, primarily due to the successful use of CRISPR/Cas9 in various types of human cells. DEG 15, a new release of the Database of Essential Genes ( www.essentialgene.org), has provided major advancements, compared to DEG 10. Specifically, the number of eukaryotic essential genes has increased by more than fourfold, and that of prokaryotic ones has more than doubled. Of note, the human essential-gene number has increased by more than tenfold. Moreover, we have developed built-in analysis modules by which users can perform various analyses, such as essential-gene distributions between bacterial leading and lagging strands, sub-cellular localization distribution, enrichment analysis of gene ontology and KEGG pathways, and generation of Venn diagrams to compare and contrast gene sets between experiments. Additionally, the database offers customizable BLAST tools for performing species- and experiment-specific BLAST searches. Therefore, DEG comprehensively harbors updated human-curated essential-gene records among prokaryotes and eukaryotes with built-in tools to enhance essential-gene analysis.

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          Most cited references126

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          clusterProfiler: an R package for comparing biological themes among gene clusters.

          Increasing quantitative data generated from transcriptomics and proteomics require integrative strategies for analysis. Here, we present an R package, clusterProfiler that automates the process of biological-term classification and the enrichment analysis of gene clusters. The analysis module and visualization module were combined into a reusable workflow. Currently, clusterProfiler supports three species, including humans, mice, and yeast. Methods provided in this package can be easily extended to other species and ontologies. The clusterProfiler package is released under Artistic-2.0 License within Bioconductor project. The source code and vignette are freely available at http://bioconductor.org/packages/release/bioc/html/clusterProfiler.html.
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            A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity.

            Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) systems provide bacteria and archaea with adaptive immunity against viruses and plasmids by using CRISPR RNAs (crRNAs) to guide the silencing of invading nucleic acids. We show here that in a subset of these systems, the mature crRNA that is base-paired to trans-activating crRNA (tracrRNA) forms a two-RNA structure that directs the CRISPR-associated protein Cas9 to introduce double-stranded (ds) breaks in target DNA. At sites complementary to the crRNA-guide sequence, the Cas9 HNH nuclease domain cleaves the complementary strand, whereas the Cas9 RuvC-like domain cleaves the noncomplementary strand. The dual-tracrRNA:crRNA, when engineered as a single RNA chimera, also directs sequence-specific Cas9 dsDNA cleavage. Our study reveals a family of endonucleases that use dual-RNAs for site-specific DNA cleavage and highlights the potential to exploit the system for RNA-programmable genome editing.
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              Multiplex genome engineering using CRISPR/Cas systems.

              Functional elucidation of causal genetic variants and elements requires precise genome editing technologies. The type II prokaryotic CRISPR (clustered regularly interspaced short palindromic repeats)/Cas adaptive immune system has been shown to facilitate RNA-guided site-specific DNA cleavage. We engineered two different type II CRISPR/Cas systems and demonstrate that Cas9 nucleases can be directed by short RNAs to induce precise cleavage at endogenous genomic loci in human and mouse cells. Cas9 can also be converted into a nicking enzyme to facilitate homology-directed repair with minimal mutagenic activity. Lastly, multiple guide sequences can be encoded into a single CRISPR array to enable simultaneous editing of several sites within the mammalian genome, demonstrating easy programmability and wide applicability of the RNA-guided nuclease technology.
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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
                23 October 2020
                23 October 2020
                : 49
                : D1
                : D677-D686
                Affiliations
                Department of Physics, School of Science, Tianjin University , Tianjin 300072, China
                Department of Physics, School of Science, Tianjin University , Tianjin 300072, China
                Department of Physics, School of Science, Tianjin University , Tianjin 300072, China
                Department of Physics, School of Science, Tianjin University , Tianjin 300072, China
                Department of Physics, School of Science, Tianjin University , Tianjin 300072, China
                Department of Physics, School of Science, Tianjin University , Tianjin 300072, China
                Frontiers Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University , Tianjin 300072, China
                Center for Molecular Medicine and Genetics, School of Medicine, Wayne State University , Detroit, MI 48201, USA
                Author notes
                To whom correspondence should be addressed. Tel: +1 313 577 0027; Fax: +1 313 577 5218; Email: rzhang@ 123456med.wayne.edu
                Correspondence may also be addressed to Feng Gao. Tel: +86 22 2740 2987; Fax: +86 22 2740 2697; Email: fgao@ 123456tju.edu.cn
                Author information
                http://orcid.org/0000-0003-2714-8817
                http://orcid.org/0000-0002-2782-3811
                http://orcid.org/0000-0002-9563-3841
                http://orcid.org/0000-0003-3844-9527
                Article
                gkaa917
                10.1093/nar/gkaa917
                7779065
                33095861
                3f6dc05a-985a-4357-ab40-26b4404423af
                © 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
                : 06 October 2020
                : 30 September 2020
                : 15 September 2020
                Page count
                Pages: 10
                Funding
                Funded by: National Key Research and Development Program of China, DOI 10.13039/501100012166;
                Award ID: 2018YFA0903700
                Funded by: National Natural Science Foundation of China, DOI 10.13039/501100001809;
                Award ID: 31801104
                Award ID: 31571358
                Award ID: 31200991
                Categories
                AcademicSubjects/SCI00010
                Database Issue

                Genetics
                Genetics

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