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      Accurate microRNA annotation of animal genomes using trained covariance models of curated microRNA complements in MirMachine

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          Summary

          The annotation of microRNAs depends on the availability of transcriptomics data and expert knowledge. This has led to a gap between the availability of novel genomes and high-quality microRNA complements. Using >16,000 microRNAs from the manually curated microRNA gene database MirGeneDB, we generated trained covariance models for all conserved microRNA families. These models are available in our tool MirMachine, which annotates conserved microRNAs within genomes. We successfully applied MirMachine to a range of animal species, including those with large genomes and genome duplications and extinct species, where small RNA sequencing is hard to achieve. We further describe a microRNA score of expected microRNAs that can be used to assess the completeness of genome assemblies. MirMachine closes a long-persisting gap in the microRNA field by facilitating automated genome annotation pipelines and deeper studies into the evolution of genome regulation, even in extinct organisms.

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          Highlights

          • An annotation pipeline using trained covariance models of microRNA families

          • Enables massive parallel annotation of microRNA complements of genomes

          • MirMachine creates meaningful annotations for very large and extinct genomes

          • microRNA score to assess genome assembly completeness

          Abstract

          By building and training covariance models from ∼16,000 manually curated microRNA genes, Umu et al. developed the microRNA annotation tool MirMachine. MirMachine can accurately annotate conserved microRNA complements directly from hundreds of genomes. This timely development opens the field of comparative regulatory genomics tapping into the explosion of genome sequencing efforts.

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          Most cited references89

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          MAFFT online service: multiple sequence alignment, interactive sequence choice and visualization

          Abstract This article describes several features in the MAFFT online service for multiple sequence alignment (MSA). As a result of recent advances in sequencing technologies, huge numbers of biological sequences are available and the need for MSAs with large numbers of sequences is increasing. To extract biologically relevant information from such data, sophistication of algorithms is necessary but not sufficient. Intuitive and interactive tools for experimental biologists to semiautomatically handle large data are becoming important. We are working on development of MAFFT toward these two directions. Here, we explain (i) the Web interface for recently developed options for large data and (ii) interactive usage to refine sequence data sets and MSAs.
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            Metazoan MicroRNAs

            MicroRNAs (miRNAs) are ∼22 nt RNAs that direct posttranscriptional repression of mRNA targets in diverse eukaryotic lineages. In humans and other mammals, these small RNAs help sculpt the expression of most mRNAs. This article reviews advances in our understanding of the defining features of metazoan miRNAs and their biogenesis, genomics, and evolution. It then reviews how metazoan miRNAs are regulated, how they recognize and cause repression of their targets, and the biological functions of this repression, with a compilation of knockout phenotypes that shows that important biological functions have been identified for most of the broadly conserved miRNAs of mammals.
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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

                Contributors
                Journal
                Cell Genom
                Cell Genom
                Cell Genomics
                Elsevier
                2666-979X
                23 June 2023
                09 August 2023
                23 June 2023
                : 3
                : 8
                : 100348
                Affiliations
                [1 ]Department of Pathology, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
                [2 ]The Arctic University Museum of Norway, UiT - The Arctic University of Norway, Tromsø, Norway
                [3 ]Independent researcher, Leipzig, Germany
                [4 ]Department of Research, Cancer Registry of Norway, Oslo, Norway
                [5 ]Centre for Bioinformatics, Department of Pharmacy, University of Oslo, Oslo, Norway
                [6 ]Department of Biological Sciences, Dartmouth College, Hanover, NH, USA
                Author notes
                []Corresponding author bastian.fromm@ 123456uit.no
                [7]

                Lead contact

                Article
                S2666-979X(23)00123-4 100348
                10.1016/j.xgen.2023.100348
                10435380
                37601971
                b82325af-b7c4-4a94-99b6-83cc1ccf2110
                © 2023 The Author(s)

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 6 December 2022
                : 15 March 2023
                : 26 May 2023
                Categories
                Technology

                micrornas,genome annotation,machine learning,evolution,genomics

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