TBI-Preprint 05-02-001
Download:
[PostScript]
[PDF]
Titel:
Fast and reliable prediction of noncoding RNAs
Author(s):
Stefan Washietl,
Ivo L. Hofacker,
Peter F. Stadler
Published in:
Proc.Natl.Acad.Sci.USA (2005)
Abstract:
We report an efficient method to detect functional RNAs. The
approach, which combines comparative sequence analysis and structure
prediction, yields excellent results already for a small number of aligned
sequences and is suitable for large scale-genomic screens. It consists of
two basic components: (1) a novel measure for RNA secondary structure
conservation based on computing a consensus secondary structure, and (2) a
measure for thermodynamic stability, which - in the spirit of a $z$-score
- is normalized w.r.t.\ both sequence length and base composition but can
be calculated without sampling from shuffled sequences. Functional RNA
secondary structures can be identified in multiple sequence alignments
with high sensitivity and high specificity. We demonstrate that this
approach is not only much more accurate than previous methods but also
significantly faster. The method is implemented in the program
RNAz
, which can be downloaded from
http://www.tbi.univie.ac.at/~wash/RNAz/.
As a first application we screened all alignments of length N> 50
in the CORG database,
which compiles conserved non-coding elements in upstream regions of
orthologous genes from human, mouse, rat fugu and zebrafish. We recovered
all of the known non-coding RNAs and cis-acting elements
with high significance and found compelling evidence for many other
conserved RNA secondary structures not described so far.
Keywords:
comparative genomics, conserved RNA secondary structure
Alternative Numbers:
Return to 2005 working papers list.
Last modified: 2005-03-25 13:41:23 ivo