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      Detecting and Comparing Non-Coding RNAs in the High-Throughput Era

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          Abstract

          In recent years there has been a growing interest in the field of non-coding RNA. This surge is a direct consequence of the discovery of a huge number of new non-coding genes and of the finding that many of these transcripts are involved in key cellular functions. In this context, accurately detecting and comparing RNA sequences has become important. Aligning nucleotide sequences is a key requisite when searching for homologous genes. Accurate alignments reveal evolutionary relationships, conserved regions and more generally any biologically relevant pattern. Comparing RNA molecules is, however, a challenging task. The nucleotide alphabet is simpler and therefore less informative than that of amino-acids. Moreover for many non-coding RNAs, evolution is likely to be mostly constrained at the structural level and not at the sequence level. This results in very poor sequence conservation impeding comparison of these molecules. These difficulties define a context where new methods are urgently needed in order to exploit experimental results to their full potential. This review focuses on the comparative genomics of non-coding RNAs in the context of new sequencing technologies and especially dealing with two extremely important and timely research aspects: the development of new methods to align RNAs and the analysis of high-throughput data.

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          Most cited references182

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          Identification of common molecular subsequences.

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            Profile hidden Markov models.

            S. Eddy (1998)
            The recent literature on profile hidden Markov model (profile HMM) methods and software is reviewed. Profile HMMs turn a multiple sequence alignment into a position-specific scoring system suitable for searching databases for remotely homologous sequences. Profile HMM analyses complement standard pairwise comparison methods for large-scale sequence analysis. Several software implementations and two large libraries of profile HMMs of common protein domains are available. HMM methods performed comparably to threading methods in the CASP2 structure prediction exercise.
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              RNA maps reveal new RNA classes and a possible function for pervasive transcription.

              Significant fractions of eukaryotic genomes give rise to RNA, much of which is unannotated and has reduced protein-coding potential. The genomic origins and the associations of human nuclear and cytosolic polyadenylated RNAs longer than 200 nucleotides (nt) and whole-cell RNAs less than 200 nt were investigated in this genome-wide study. Subcellular addresses for nucleotides present in detected RNAs were assigned, and their potential processing into short RNAs was investigated. Taken together, these observations suggest a novel role for some unannotated RNAs as primary transcripts for the production of short RNAs. Three potentially functional classes of RNAs have been identified, two of which are syntenically conserved and correlate with the expression state of protein-coding genes. These data support a highly interleaved organization of the human transcriptome.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                Molecular Diversity Preservation International (MDPI)
                1422-0067
                August 2013
                24 July 2013
                : 14
                : 8
                : 15423-15458
                Affiliations
                [1 ]European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK; E-Mail: aje@ 123456ebi.ac.uk
                [2 ]Bioinformatics and Genomics Program, Centre for Genomic Regulation (CRG), Aiguader, 88, 08003 Barcelona, Spain; E-Mail: Cedric.Notredame@ 123456crg.eu
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: giovanni.bussotti@ 123456ebi.ac.uk ; Tel.: +44-1223-49-2680 (ext. 2680); Fax: +44-1223-49-4486.
                Article
                ijms-14-15423
                10.3390/ijms140815423
                3759867
                23887659
                6f6aa1bb-04b5-40cd-801a-513ea837aa04
                © 2013 by the authors; licensee MDPI, Basel, Switzerland

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                : 31 May 2013
                : 16 July 2013
                : 17 July 2013
                Categories
                Review

                Molecular biology
                lncrnas,ncrnas,high-throughput,rna-seq,comparative biology,sequencing
                Molecular biology
                lncrnas, ncrnas, high-throughput, rna-seq, comparative biology, sequencing

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