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      Towards a piRNA prediction using multiple kernel fusion and support vector machine

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          Abstract

          Motivation: Piwi-interacting RNA (piRNA) is the most recently discovered and the least investigated class of Argonaute/Piwi protein-interacting small non-coding RNAs. The piRNAs are mostly known to be involved in protecting the genome from invasive transposable elements. But recent discoveries suggest their involvement in the pathophysiology of diseases, such as cancer. Their identification is therefore an important task, and computational methods are needed. However, the lack of conserved piRNA sequences and structural elements makes this identification challenging and difficult.

          Results: In the present study, we propose a new modular and extensible machine learning method based on multiple kernels and a support vector machine (SVM) classifier for piRNA identification. Very few piRNA features are known to date. The use of a multiple kernels approach allows editing, adding or removing piRNA features that can be heterogeneous in a modular manner according to their relevance in a given species. Our algorithm is based on a combination of the previously identified features [sequence features (k-mer motifs and a uridine at the first position) and piRNAs cluster feature] and a new telomere/centromere vicinity feature. These features are heterogeneous, and the kernels allow to unify their representation. The proposed algorithm, named piRPred, gives promising results on Drosophila and Human data and outscores previously published piRNA identification algorithms.

          Availability and implementation: piRPred is freely available to non-commercial users on our Web server EvryRNA http://EvryRNA.ibisc.univ-evry.fr

          Contact: tahi@ 123456ibisc.univ-evry.fr

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          Most cited references34

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          LIBSVM: A library for support vector machines

          LIBSVM is a library for Support Vector Machines (SVMs). We have been actively developing this package since the year 2000. The goal is to help users to easily apply SVM to their applications. LIBSVM has gained wide popularity in machine learning and many other areas. In this article, we present all implementation details of LIBSVM. Issues such as solving SVM optimization problems theoretical convergence multiclass classification probability estimates and parameter selection are discussed in detail.
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            A germline-specific class of small RNAs binds mammalian Piwi proteins.

            Small RNAs associate with Argonaute proteins and serve as sequence-specific guides to regulate messenger RNA stability, protein synthesis, chromatin organization and genome structure. In animals, Argonaute proteins segregate into two subfamilies. The Argonaute subfamily acts in RNA interference and in microRNA-mediated gene regulation using 21-22-nucleotide RNAs as guides. The Piwi subfamily is involved in germline-specific events such as germline stem cell maintenance and meiosis. However, neither the biochemical function of Piwi proteins nor the nature of their small RNA guides is known. Here we show that MIWI, a murine Piwi protein, binds a previously uncharacterized class of approximately 29-30-nucleotide RNAs that are highly abundant in testes. We have therefore named these Piwi-interacting RNAs (piRNAs). piRNAs show distinctive localization patterns in the genome, being predominantly grouped into 20-90-kilobase clusters, wherein long stretches of small RNAs are derived from only one strand. Similar piRNAs are also found in human and rat, with major clusters occurring in syntenic locations. Although their function must still be resolved, the abundance of piRNAs in germline cells and the male sterility of Miwi mutants suggest a role in gametogenesis.
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              A novel class of small RNAs bind to MILI protein in mouse testes.

              Small RNAs bound to Argonaute proteins recognize partially or fully complementary nucleic acid targets in diverse gene-silencing processes. A subgroup of the Argonaute proteins--known as the 'Piwi family'--is required for germ- and stem-cell development in invertebrates, and two Piwi members--MILI and MIWI--are essential for spermatogenesis in mouse. Here we describe a new class of small RNAs that bind to MILI in mouse male germ cells, where they accumulate at the onset of meiosis. The sequences of the over 1,000 identified unique molecules share a strong preference for a 5' uridine, but otherwise cannot be readily classified into sequence families. Genomic mapping of these small RNAs reveals a limited number of clusters, suggesting that these RNAs are processed from long primary transcripts. The small RNAs are 26-31 nucleotides (nt) in length--clearly distinct from the 21-23 nt of microRNAs (miRNAs) or short interfering RNAs (siRNAs)--and we refer to them as 'Piwi-interacting RNAs' or piRNAs. Orthologous human chromosomal regions also give rise to small RNAs with the characteristics of piRNAs, but the cloned sequences are distinct. The identification of this new class of small RNAs provides an important starting point to determine the molecular function of Piwi proteins in mammalian spermatogenesis.
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                Author and article information

                Journal
                Bioinformatics
                Bioinformatics
                bioinformatics
                bioinfo
                Bioinformatics
                Oxford University Press
                1367-4803
                1367-4811
                01 September 2014
                22 August 2014
                22 August 2014
                : 30
                : 17
                : i364-i370
                Affiliations
                1IBISC EA 4526, UEVE/Genopole, IBGBI, 23 bv. de France, 91000 Evry, France and 2Genethon, 1, bis rue de l’Internationale, 91002 Evry Cedex, France
                Author notes
                *To whom correspondence should be addressed.
                Article
                btu441
                10.1093/bioinformatics/btu441
                4147894
                25161221
                03b10702-b21b-4fd9-b46a-f2f5564acd1f
                © The Author 2014. Published by Oxford University Press.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                Page count
                Pages: 7
                Categories
                Eccb 2014 Proceedings Papers Committee
                Original Papers
                Sequencing and Sequence Analysis for Genomics

                Bioinformatics & Computational biology
                Bioinformatics & Computational biology

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