Genomics GM_D0005

Title : Consensus Folding of Aligned Sequences as a New Measure for the Detection of Functional RNAs by Comparative Genomics
Author : Stefan Washietl and Ivo L. Hofacker
Year : 2004
Place of publish : JMB Scince Direct ELSEVIER
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 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 Caenorhabditis elegans/Caenorhabditis
briggsae and seven Saccharomyces species. Most RNAs can be detected
with high significance. We provide a Perl implementation that can be used
readily to score single alignments and discuss how the methods described
here can be extended to allow for efficient genome-wide screens.