LocARNA-P: Accurate boundary prediction and improved detection of structural RNAs

Sebastian Will, Tejal Joshi, Ivo L. Hofacker, Peter F. Stadler, Rolf Backofen

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    Abstract

    Current genomic screens for noncoding RNAs (ncRNAs) predict a large number of genomic regions containing potential structural ncRNAs. The analysis of these data requires highly accurate prediction of ncRNA boundaries and discrimination of promising candidate ncRNAs from weak predictions. Existing methods struggle with these goals because they rely on sequence-based multiple sequence alignments, which regularly misalign RNA structure and therefore do not support identification of structural similarities. To overcome this limitation, we compute columnwise and global reliabilities of alignments based on sequence and structure similarity; we refer to these structure-based alignment reliabilities as STARs. The columnwise STARs of alignments, or STAR profiles, provide a versatile tool for the manual and automatic analysis of ncRNAs. In particular, we improve the boundary prediction of the widely used ncRNA gene finder RNAz by a factor of 3 from a median deviation of 47 to 13 nt. Post-processing RNAz predictions, LocARNA-P's STAR score allows much stronger discrimination between true- and false-positive predictions than RNAz's own evaluation. The improved accuracy, in this scenario increased from AUC 0.71 to AUC 0.87, significantly reduces the cost of successive analysis steps. The ready-to-use software tool LocARNA-P produces structure-based multiple RNA alignments with associated columnwise STARs and predicts ncRNA boundaries. We provide additional results, a web server for LocARNA/LocARNA-P, and the software package, including documentation and a pipeline for refining screens for structural ncRNA, at http://www.bioinf.uni-freiburg.de/Supplements/LocARNA-P/.
    Original languageEnglish
    JournalR N A
    Volume18
    Issue number5
    Pages (from-to)900-914
    ISSN1355-8382
    DOIs
    Publication statusPublished - 2012

    Bibliographical note

    Downloaded from rnajournal.cshlp.org on June 19, 2012 - Published by Cold Spring Harbor Laboratory Press

    Keywords

    • boundary prediction
    • columnwise reliability
    • global reliability
    • Primates Mammalia Vertebrata Chordata Animalia (Animals, Chordates, Humans, Mammals, Primates, Vertebrates) - Hominidae [86215] human common
    • human ncRNA gene [Hominidae]
    • noncoding RNA ncRNA
    • 00530, General biology - Information, documentation, retrieval and computer applications
    • 03502, Genetics - General
    • 03508, Genetics - Human
    • 04500, Mathematical biology and statistical methods
    • Biochemistry and Molecular Biophysics
    • Computational Biology
    • LocARNA-P computer software
    • sequence-structure-based alignment reliability STAR mathematical and computer techniques
    • Computer Applications
    • Mathematical Biology
    • Molecular Genetics

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