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      Prediction of Mature MicroRNA and Piwi-Interacting RNA without a Genome Reference or Precursors

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          Abstract

          The discovery of novel microRNA (miRNA) and piwi-interacting RNA (piRNA) is an important task for the understanding of many biological processes. Most of the available miRNA and piRNA identification methods are dependent on the availability of the organism’s genome sequence and the quality of its annotation. Therefore, an efficient prediction method based solely on the short RNA reads and requiring no genomic information is highly desirable. In this study, we propose an approach that relies primarily on the nucleotide composition of the read and does not require reference genomes of related species for prediction. Using an empirical Bayesian kernel method and the error correcting output codes framework, compact models suitable for large-scale analyses are built on databases of known mature miRNAs and piRNAs. We found that the usage of an L 1-based Gaussian kernel can double the true positive rate compared to the standard L 2-based Gaussian kernel. Our approach can increase the true positive rate by at most 60% compared to the existing piRNA predictor based on the analysis of a hold-out test set. Using experimental data, we also show that our approach can detect about an order of magnitude or more known miRNAs than the mature miRNA predictor, miRPlex.

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          Most cited references24

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          NCBI GEO: archive for functional genomics data sets—update

          The Gene Expression Omnibus (GEO, http://www.ncbi.nlm.nih.gov/geo/) is an international public repository for high-throughput microarray and next-generation sequence functional genomic data sets submitted by the research community. The resource supports archiving of raw data, processed data and metadata which are indexed, cross-linked and searchable. All data are freely available for download in a variety of formats. GEO also provides several web-based tools and strategies to assist users to query, analyse and visualize data. This article reports current status and recent database developments, including the release of GEO2R, an R-based web application that helps users analyse GEO data.
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            The deep evolution of metazoan microRNAs.

            microRNAs (miRNAs) are approximately 22-nucleotide noncoding RNA regulatory genes that are key players in cellular differentiation and homeostasis. They might also play important roles in shaping metazoan macroevolution. Previous studies have shown that miRNAs are continuously being added to metazoan genomes through time, and, once integrated into gene regulatory networks, show only rare mutations within the primary sequence of the mature gene product and are only rarely secondarily lost. However, because the conclusions from these studies were largely based on phylogenetic conservation of miRNAs between model systems like Drosophila and the taxon of interest, it was unclear if these trends would describe most miRNAs in most metazoan taxa. Here, we describe the shared complement of miRNAs among 18 animal species using a combination of 454 sequencing of small RNA libraries with genomic searches. We show that the evolutionary trends elucidated from the model systems are generally true for all miRNA families and metazoan taxa explored: the continuous addition of miRNA families with only rare substitutions to the mature sequence, and only rare instances of secondary loss. Despite this conservation, we document evolutionary stable shifts to the determination of position 1 of the mature sequence, a phenomenon we call seed shifting, as well as the ability to post-transcriptionally edit the 5' end of the mature read, changing the identity of the seed sequence and possibly the repertoire of downstream targets. Finally, we describe a novel type of miRNA in demosponges that, although shows a different pre-miRNA structure, still shows remarkable conservation of the mature sequence in the two sponge species analyzed. We propose that miRNAs might be excellent phylogenetic markers, and suggest that the advent of morphological complexity might have its roots in miRNA innovation.
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              miRNA profiling of cancer.

              A steadily growing number of studies have shown that microRNAs have key roles in the regulation of cellular processes and that their dysregulation is essential to keep the malignant phenotype of cancer cells. The distorted and unique expression profile of microRNAs in different types and subsets of tumor coupled with their presence in biological fluids make of microRNAs an attractive source of sensitive biomarkers. Here, we will discuss how microRNA profiles are altered in cancer, highlighting their potential as sensitive biomarkers for cancer risk stratification, outcome prediction and classification of histological subtypes. We will also evaluate the current knowledge on the use of microRNAs as circulating biomarkers, hoping that further studies will lead to the application of microRNA signature in prognostic and predictive markers that can improve patient health. Copyright © 2013 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                08 January 2015
                January 2015
                : 16
                : 1
                : 1466-1481
                Affiliations
                Department of Information and Computer Sciences, University of Hawaii at Mānoa, 1680 East-West Road, Honolulu, HI 96822, USA; E-Mail: mmenor@ 123456hawaii.edu
                Author notes
                [* ]Authors to whom correspondence should be addressed; E-Mails: kyungim@ 123456hawaii.edu (K.B.); guylaine@ 123456hawaii.edu (G.P.); Tel.: +1-808-956-8560 (K.B.); +1-808-956-3496 (G.P.); Fax: +1-808-956-3548 (K.B. & G.P.).
                Article
                ijms-16-01466
                10.3390/ijms16011466
                4307313
                25580537
                6839099c-c4b7-4657-b70d-cd9b9a9ca9a0
                © 2015 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/4.0/).

                History
                : 31 October 2014
                : 05 January 2015
                Categories
                Article

                Molecular biology
                microrna,piwi-interacting rna,non-coding rnas,kernel machine,classification
                Molecular biology
                microrna, piwi-interacting rna, non-coding rnas, kernel machine, classification

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