TBI-Preprint 04-04-001
Download:
[PostScript]
[PDF]
Titel:
Consensus folding of aligned sequences as a new measure for the detection
of functional RNAs by comparative genomics
Author(s):
Stefan Washietl,
Ivo L. Hofacker
appeared in:
J Mol Biol 342: 19-30 (2004).
Abstract:
Facing the ever-growing list of newly discovered classes of functional
RNAs, it can be expected that further types of functional RNAs are still
hidden in recently completed genomes. The computational identification of
such RNA genes is, therefore, of major importance. While most known
functional RNAs have characteristic secondary structures, their free
energies are generally not statistically significant enough to distinguish
RNA genes from the genomic background. Additional information is
required. Considering the wide availability of new genomic data of closely
related species, comparative studies seem to be the most promising
approach. Here we show that prediction of consensus structures of aligned
sequences can be a significant measure to detect functional RNAs. We report
a new method how to test multiple sequence alignments for the existence of
an unusually structured and conserved fold. We show for alignments of six
types of well known functional RNA that an energy score consisting of free
energy and a covariation term significantly improves sensitivity compared
to single sequence predictions. We further test our method on a number of
non coding RNAs from C. elegans}/C. briggsae and seven
Saccharomyces species. Most RNAs can be detected with high significance. We
provide a Perl implementation which can be readily used to score single
alignments and discuss how the methods described here can be extended to
allow for efficient genome-wide screens.
Keywords: Minimum free energy folding, consensus secondary structure prediction, non coding RNAs, comparative genomics, randomizing multiple sequence alignments
Return to 2004 working papers list.
Last modified: 2004-08-30 11:13:24 ivo