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SnoReport: Computational identification of snoRNAs with unknown targets

: Hertel, J.; Hofacker, I.L.; Stadler, P.F.


Bioinformatics 24 (2008), No.2, pp.158-164
ISSN: 1367-4803
ISSN: 1460-2059
Journal Article
Fraunhofer IZI ()

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 so far have explicitly used the fact that snoRNAs predominantly target ribosomal RNAs and spliceosomal RNAs. The target 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 widespread 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 CD and box HACA 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.