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      miRWalk: An online resource for prediction of microRNA binding sites

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      PLoS ONE
      Public Library of Science

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          Abstract

          miRWalk is an open-source platform providing an intuitive interface that generates predicted and validated miRNA-binding sites of known genes of human, mouse, rat, dog and cow. The core of miRWalk is the miRNA target site prediction with the random-forest-based approach software TarPmiR searching the complete transcript sequence including the 5’-UTR, CDS and 3’-UTR. Moreover, it integrates results other databases with predicted and validated miRNA-target interactions. The focus is set on a modular design and extensibility as well as a fast update cycle. The database is available using Python, MySQL and HTML/Javascript Database URL: http://mirwalk.umm.uni-heidelberg.de.

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          Using expression profiling data to identify human microRNA targets.

          We demonstrate that paired expression profiles of microRNAs (miRNAs) and mRNAs can be used to identify functional miRNA-target relationships with high precision. We used a Bayesian data analysis algorithm, GenMiR++, to identify a network of 1,597 high-confidence target predictions for 104 human miRNAs, which was supported by RNA expression data across 88 tissues and cell types, sequence complementarity and comparative genomics data. We experimentally verified our predictions by investigating the result of let-7b downregulation in retinoblastoma using quantitative reverse transcriptase (RT)-PCR and microarray profiling: some of our verified let-7b targets include CDC25A and BCL7A. Compared to sequence-based predictions, our high-scoring GenMiR++ predictions had much more consistent Gene Ontology annotations and were more accurate predictors of which mRNA levels respond to changes in let-7b levels.
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            miRWalk database for miRNA-target interactions.

            miRWalk (http://mirwalk.uni-hd.de/) is a publicly available comprehensive resource, hosting the predicted as well as the experimentally validated microRNA (miRNA)-target interaction pairs. This database allows obtaining the possible miRNA-binding site predictions within the complete sequence of all known genes of three genomes (human, mouse, and rat). Moreover, it also integrates many novel features such as a comparative platform of miRNA-binding sites resulting from ten different prediction datasets, a holistic view of genetic networks of miRNA-gene pathway, and miRNA-gene-Online Mendelian Inheritance in Man disorder interactions, and unique experimentally validated information (e.g., cell lines, diseases, miRNA processing proteins). In this chapter, we describe a schematic workflow on how one can access the stored information from miRWalk and subsequently summarize its applications.
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              TarPmiR: a new approach for microRNA target site prediction

              Motivation: The identification of microRNA (miRNA) target sites is fundamentally important for studying gene regulation. There are dozens of computational methods available for miRNA target site prediction. Despite their existence, we still cannot reliably identify miRNA target sites, partially due to our limited understanding of the characteristics of miRNA target sites. The recently published CLASH (crosslinking ligation and sequencing of hybrids) data provide an unprecedented opportunity to study the characteristics of miRNA target sites and improve miRNA target site prediction methods. Results: Applying four different machine learning approaches to the CLASH data, we identified seven new features of miRNA target sites. Combining these new features with those commonly used by existing miRNA target prediction algorithms, we developed an approach called TarPmiR for miRNA target site prediction. Testing on two human and one mouse non-CLASH datasets, we showed that TarPmiR predicted more than 74.2% of true miRNA target sites in each dataset. Compared with three existing approaches, we demonstrated that TarPmiR is superior to these existing approaches in terms of better recall and better precision. Availability and Implementation: The TarPmiR software is freely available at http://hulab.ucf.edu/research/projects/miRNA/TarPmiR/. Contacts: haihu@cs.ucf.edu or xiaoman@mail.ucf.edu Supplementary information: Supplementary data are available at Bioinformatics online.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: MethodologyRole: SoftwareRole: Writing – original draft
                Role: Data curationRole: ResourcesRole: Writing – review & editing
                Role: ResourcesRole: SoftwareRole: Writing – review & editing
                Role: ConceptualizationRole: Project administrationRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                18 October 2018
                2018
                : 13
                : 10
                : e0206239
                Affiliations
                [001]Medical Research Center, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
                Ohio State University, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0003-3596-6094
                Article
                PONE-D-18-17953
                10.1371/journal.pone.0206239
                6193719
                30335862
                a4126443-f1dc-41a4-9b8f-076083e9ad84
                © 2018 Sticht et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 15 June 2018
                : 9 October 2018
                Page count
                Figures: 2, Tables: 0, Pages: 6
                Funding
                The author(s) received no specific funding for this work.
                Categories
                Research Article
                Biology and life sciences
                Biochemistry
                Nucleic acids
                RNA
                Non-coding RNA
                Natural antisense transcripts
                MicroRNAs
                Biology and life sciences
                Genetics
                Gene expression
                Gene regulation
                MicroRNAs
                Research and Analysis Methods
                Database and Informatics Methods
                Biological Databases
                Sequence Databases
                Research and Analysis Methods
                Database and Informatics Methods
                Bioinformatics
                Sequence Analysis
                Sequence Databases
                Physical Sciences
                Mathematics
                Applied Mathematics
                Algorithms
                Machine Learning Algorithms
                Research and Analysis Methods
                Simulation and Modeling
                Algorithms
                Machine Learning Algorithms
                Computer and Information Sciences
                Artificial Intelligence
                Machine Learning
                Machine Learning Algorithms
                Research and Analysis Methods
                Database and Informatics Methods
                Database Searching
                Physical Sciences
                Mathematics
                Applied Mathematics
                Algorithms
                Research and Analysis Methods
                Simulation and Modeling
                Algorithms
                Biology and Life Sciences
                Genetics
                Genomics
                Animal Genomics
                Mammalian Genomics
                Research and Analysis Methods
                Database and Informatics Methods
                Biological Databases
                Genomic Databases
                Biology and Life Sciences
                Computational Biology
                Genome Analysis
                Genomic Databases
                Biology and Life Sciences
                Genetics
                Genomics
                Genome Analysis
                Genomic Databases
                Computer and Information Sciences
                Computer Applications
                Web-Based Applications
                Custom metadata
                All data can be accessed via the website http://mirwalk.umm.uni-heidelberg.de. Complete sets can be downloaded under "Resources".

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