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      Bioinformatic Tools for the Identification of MicroRNAs Regulating the Transcription Factors in Patients with β-Thalassemia

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          Abstract

          β-thalassemia is a significant health issue worldwide, with approximately 7% of the world’s population having defective hemoglobin genes. MicroRNAs (miRNAs) are short noncoding RNAs regulating gene expression at the post-transcriptional level by targeting multiple gene transcripts. The levels of fetal hemoglobin (HbF) can be increased by regulating the expression of the γ-globin gene using the suppressive effects of miRNAs on several transcription factors such as MYB, BCL11A, GATA1, and KLF. An early step in discovering miRNA:mRNA target interactions is the computational prediction of miRNA targets that can be later validated with wet-lab investigations. This review highlights some commonly employed computational tools such as miRBase, Target scan, DIANA-microT-CDS, miRwalk, miRDB, and micro-TarBase that can be used to predict miRNA targets. Upon comparing the miRNA target prediction tools, 4 main aspects of the miRNA:mRNA target interaction are shown to include a few common features on which most target prediction is based: conservation sites, seed match, free energy, and site accessibility. Understanding these prediction tools’ usage will help users select the appropriate tool and interpret the results accurately. This review will, therefore, be helpful to peers to quickly choose a list of the best miRNAs associated with HbF induction. Researchers will obtain significant results using these bioinformatics tools to establish a new important concept in managing β-thalassemia and delivering therapeutic strategies for improving their quality of life.

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          Most cited references76

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          Predicting effective microRNA target sites in mammalian mRNAs

          MicroRNA targets are often recognized through pairing between the miRNA seed region and complementary sites within target mRNAs, but not all of these canonical sites are equally effective, and both computational and in vivo UV-crosslinking approaches suggest that many mRNAs are targeted through non-canonical interactions. Here, we show that recently reported non-canonical sites do not mediate repression despite binding the miRNA, which indicates that the vast majority of functional sites are canonical. Accordingly, we developed an improved quantitative model of canonical targeting, using a compendium of experimental datasets that we pre-processed to minimize confounding biases. This model, which considers site type and another 14 features to predict the most effectively targeted mRNAs, performed significantly better than existing models and was as informative as the best high-throughput in vivo crosslinking approaches. It drives the latest version of TargetScan (v7.0; targetscan.org), thereby providing a valuable resource for placing miRNAs into gene-regulatory networks. DOI: http://dx.doi.org/10.7554/eLife.05005.001
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            miRBase: from microRNA sequences to function

            Abstract miRBase catalogs, names and distributes microRNA gene sequences. The latest release of miRBase (v22) contains microRNA sequences from 271 organisms: 38 589 hairpin precursors and 48 860 mature microRNAs. We describe improvements to the database and website to provide more information about the quality of microRNA gene annotations, and the cellular functions of their products. We have collected 1493 small RNA deep sequencing datasets and mapped a total of 5.5 billion reads to microRNA sequences. The read mapping patterns provide strong support for the validity of between 20% and 65% of microRNA annotations in different well-studied animal genomes, and evidence for the removal of >200 sequences from the database. To improve the availability of microRNA functional information, we are disseminating Gene Ontology terms annotated against miRBase sequences. We have also used a text-mining approach to search for microRNA gene names in the full-text of open access articles. Over 500 000 sentences from 18 542 papers contain microRNA names. We score these sentences for functional information and link them with 12 519 microRNA entries. The sentences themselves, and word clouds built from them, provide effective summaries of the functional information about specific microRNAs. miRBase is publicly and freely available at http://mirbase.org/.
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              ViennaRNA Package 2.0

              Background Secondary structure forms an important intermediate level of description of nucleic acids that encapsulates the dominating part of the folding energy, is often well conserved in evolution, and is routinely used as a basis to explain experimental findings. Based on carefully measured thermodynamic parameters, exact dynamic programming algorithms can be used to compute ground states, base pairing probabilities, as well as thermodynamic properties. Results The ViennaRNA Package has been a widely used compilation of RNA secondary structure related computer programs for nearly two decades. Major changes in the structure of the standard energy model, the Turner 2004 parameters, the pervasive use of multi-core CPUs, and an increasing number of algorithmic variants prompted a major technical overhaul of both the underlying RNAlib and the interactive user programs. New features include an expanded repertoire of tools to assess RNA-RNA interactions and restricted ensembles of structures, additional output information such as centroid structures and maximum expected accuracy structures derived from base pairing probabilities, or z-scores for locally stable secondary structures, and support for input in fasta format. Updates were implemented without compromising the computational efficiency of the core algorithms and ensuring compatibility with earlier versions. Conclusions The ViennaRNA Package 2.0, supporting concurrent computations via OpenMP, can be downloaded from http://www.tbi.univie.ac.at/RNA.
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                Author and article information

                Journal
                Bioinform Biol Insights
                Bioinform Biol Insights
                BBI
                spbbi
                Bioinformatics and Biology Insights
                SAGE Publications (Sage UK: London, England )
                1177-9322
                3 August 2022
                2022
                : 16
                : 11779322221115536
                Affiliations
                [1 ]Center for Medical Genomics & Counselling, Department of Biochemistry, JSS Medical College, JSS Academy of Higher Education and Research, Mysore, India
                [2 ]Department of Pathology, JSS Medical College, JSS Academy of Higher Education and Research, Mysore, India
                [3 ]Special Interest Group—Human Genomics & Rare Disorders (SIG-HGRD), JSS Academy of Higher Education and Research, Mysore, India
                Author notes
                [*]Akila Prashant, Center for Medical Genomics & Counselling, Department of Biochemistry, JSS Medical College, JSS Academy of Higher Education and Research, Mysore 570015, Karnataka, India. Email: akilaprashant@ 123456jssuni.edu.in
                Article
                10.1177_11779322221115536
                10.1177/11779322221115536
                9354123
                35935529
                64efe3ad-881f-4d9d-8c3d-285294e59038
                © The Author(s) 2022

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 26 April 2022
                : 2 July 2022
                Funding
                Funded by: Indian Council of Medical Research, FundRef https://doi.org/10.13039/501100001411;
                Award ID: ICMR-SRF 2021-12167
                Funded by: Department of Science and Technology, ;
                Award ID: SR/PURSE/2021/81 (G)
                Funded by: jss academy of higher education and research, FundRef https://doi.org/10.13039/100019751;
                Award ID: JSSAHER/REG/RES/URG/54/2011-12/10419
                Categories
                Review
                Custom metadata
                January-December 2022
                ts1

                Bioinformatics & Computational biology
                bioinformatics,beta-thalassemia,hemoglobinopathy,micrornas,gamma-globin

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