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      miEAA 2.0: integrating multi-species microRNA enrichment analysis and workflow management systems

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          Abstract

          Gene set enrichment analysis has become one of the most frequently used applications in molecular biology research. Originally developed for gene sets, the same statistical principles are now available for all omics types. In 2016, we published the miRNA enrichment analysis and annotation tool (miEAA) for human precursor and mature miRNAs. Here, we present miEAA 2.0, supporting miRNA input from ten frequently investigated organisms. To facilitate inclusion of miEAA in workflow systems, we implemented an Application Programming Interface (API). Users can perform miRNA set enrichment analysis using either the web-interface, a dedicated Python package, or custom remote clients. Moreover, the number of category sets was raised by an order of magnitude. We implemented novel categories like annotation confidence level or localisation in biological compartments. In combination with the miRBase miRNA-version and miRNA-to-precursor converters, miEAA supports research settings where older releases of miRBase are in use. The web server also offers novel comprehensive visualizations such as heatmaps and running sum curves with background distributions. We demonstrate the new features with case studies for human kidney cancer, a biomarker study on Parkinson’s disease from the PPMI cohort, and a mouse model for breast cancer. The tool is freely accessible at: https://www.ccb.uni-saarland.de/mieaa2.

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          Most cited references27

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          miRTarBase 2020: updates to the experimentally validated microRNA–target interaction database

          Abstract MicroRNAs (miRNAs) are small non-coding RNAs (typically consisting of 18–25 nucleotides) that negatively control expression of target genes at the post-transcriptional level. Owing to the biological significance of miRNAs, miRTarBase was developed to provide comprehensive information on experimentally validated miRNA–target interactions (MTIs). To date, the database has accumulated >13,404 validated MTIs from 11,021 articles from manual curations. In this update, a text-mining system was incorporated to enhance the recognition of MTI-related articles by adopting a scoring system. In addition, a variety of biological databases were integrated to provide information on the regulatory network of miRNAs and its expression in blood. Not only targets of miRNAs but also regulators of miRNAs are provided to users for investigating the up- and downstream regulations of miRNAs. Moreover, the number of MTIs with high-throughput experimental evidence increased remarkably (validated by CLIP-seq technology). In conclusion, these improvements promote the miRTarBase as one of the most comprehensively annotated and experimentally validated miRNA–target interaction databases. The updated version of miRTarBase is now available at http://miRTarBase.cuhk.edu.cn/.
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            An integrated expression atlas of miRNAs and their promoters in human and mouse

            An atlas of microRNA expression patterns and regulators is produced by deep sequencing of short RNAs in human and mouse cells.
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              An estimate of the total number of true human miRNAs

              Abstract While the number of human miRNA candidates continuously increases, only a few of them are completely characterized and experimentally validated. Toward determining the total number of true miRNAs, we employed a combined in silico high- and experimental low-throughput validation strategy. We collected 28 866 human small RNA sequencing data sets containing 363.7 billion sequencing reads and excluded falsely annotated and low quality data. Our high-throughput analysis identified 65% of 24 127 mature miRNA candidates as likely false-positives. Using northern blotting, we experimentally validated miRBase entries and novel miRNA candidates. By exogenous overexpression of 108 precursors that encode 205 mature miRNAs, we confirmed 68.5% of the miRBase entries with the confirmation rate going up to 94.4% for the high-confidence entries and 18.3% of the novel miRNA candidates. Analyzing endogenous miRNAs, we verified the expression of 8 miRNAs in 12 different human cell lines. In total, we extrapolated 2300 true human mature miRNAs, 1115 of which are currently annotated in miRBase V22. The experimentally validated miRNAs will contribute to revising targetomes hypothesized by utilizing falsely annotated miRNAs.
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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
                02 July 2020
                06 May 2020
                06 May 2020
                : 48
                : W1
                : W521-W528
                Affiliations
                Chair for Clinical Bioinformatics, Saarland University , 66123 Saarbrücken, Germany
                Chair for Clinical Bioinformatics, Saarland University , 66123 Saarbrücken, Germany
                Chair for Clinical Bioinformatics, Saarland University , 66123 Saarbrücken, Germany
                Chair for Clinical Bioinformatics, Saarland University , 66123 Saarbrücken, Germany
                Chair for Clinical Bioinformatics, Saarland University , 66123 Saarbrücken, Germany
                Chair for Clinical Bioinformatics, Saarland University , 66123 Saarbrücken, Germany
                Neurogenomics Division, Translational Genomics Research Institute , Phoenix, AZ 85004, USA
                Institute of Translational Genomics, University of Southern California , Los Angeles, CA 90033, USA
                Department of Human Genetics, Saarland University , 66421 Homburg, Germany
                Chair for Clinical Bioinformatics, Saarland University , 66123 Saarbrücken, Germany
                School of Medicine Office, Stanford University , Stanford, CA 94305, USA
                Department of Neurology and Neurological Sciences, Stanford University , Stanford, CA 94304, USA
                Author notes
                To whom correspondence should be addressed. Tel: +49 681 302 68611; Email: andreas.keller@ 123456ccb.uni-saarland.de

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

                Author information
                http://orcid.org/0000-0002-8223-3750
                http://orcid.org/0000-0003-1967-2918
                http://orcid.org/0000-0002-4845-2757
                http://orcid.org/0000-0001-9330-9290
                http://orcid.org/0000-0003-2040-1955
                http://orcid.org/0000-0001-7569-819X
                http://orcid.org/0000-0002-5361-0895
                Article
                gkaa309
                10.1093/nar/gkaa309
                7319446
                32374865
                4973a43e-5a61-492f-8bfd-e6287114341b
                © 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 Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@ 123456oup.com

                History
                : 22 April 2020
                : 06 April 2020
                : 05 March 2020
                Page count
                Pages: 8
                Funding
                Funded by: Michael J. Fox Foundation, DOI 10.13039/100000864;
                Award ID: 14446
                Categories
                AcademicSubjects/SCI00010
                Web Server Issue

                Genetics
                Genetics

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