Bioinformatics Preprint 05-003
Fast and reliable prediction of noncoding RNAs
Stefan Washietl, Ivo L. Hofacker, Peter F. Stadler
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.
comparative genomics, conserved RNA secondary structure
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