Bioinformatics Preprint 07-015
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Titel:
SnoReport: Computational identification of snoRNAs with unknown targets
Author(s):
Jana Hertel,
Ivo L. Hofacker,
Peter F. Stadler
Submitted
Abstract:
Unlike tRNAs and microRNAs, both classes of snoRNAs, which direct two
distinct types of chemical modifications of uracil residues, have proved to
be surprisingly difficult to find in genomic sequences. Most computational
approaches have so far explicitly used the fact that they predominantly
target ribosomal RNAs and spliceosomal RNAs. The target U is specified by a
short stretch of sequence complementarity between the snoRNA and its
target. This sequence complementarity to known targets crucially
contributes to sensitivity and specificity of snoRNA gene finding
algorithms.
The discovery of ``orphan'' snoRNAs, which either have no known target, or
which target ordinary protein-coding mRNAs, however, begs the question
whether this class of ``housekeeping'' non-coding RNAs is much more
wide-spread and might have a diverse set of regulatory functions. In order to
approach this question, we present here a combination of RNA secondary
structure prediction and machine learning that is designed to recognize the
two major classes of snoRNAs, box C/D and box H/ACA snoRNAs, among ncRNA
candidate sequences. The snoReport approach deliberately avoids
any usage of target information. We find that the combination of the
conserved sequence boxes and secondary structure constraints as a
pre-filter with SVM classifiers based on a small set of structural
descriptors are sufficient for a reliable identification of snoRNAs.
Tests of snoReport on data from several recent experimental
surveys show that the approach is feasible; the application to a dataset
from a large-scale comparative genomics survey for ncRNAs suggests
that there are likely hundreds of previously undescribed ``orphan''
snoRNAs still hidden in the human genome.
Availability:
The snoReport software is implemented in ANSI C. The
source code and supplemental material is available for download from
http://www.bioinf.uni-leipzig.de/Software/snoReport.
Keywords:
snoRNA, prediction, ncRNAs, RNA secondary structure, SVM
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Last modified: 2006-08-09 15:54:23 xtof