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Fast and reliable prediction of noncoding RNAs.

TitleFast and reliable prediction of noncoding RNAs.
Publication TypeJournal Article
Year of Publication2005
AuthorsWashietl S, Hofacker IL, Stadler PF
JournalProc Natl Acad Sci U S A
Volume102
Issue7
Pagination2454-9
Date Published2005 Feb 15
ISSN0027-8424
KeywordsAlgorithms, Databases, Nucleic Acid, Nucleic Acid Conformation, RNA Stability, RNA, Untranslated, Sequence Alignment, Software, Thermodynamics
Abstract

We report an efficient method for detecting functional RNAs. The approach, which combines comparative sequence analysis and structure prediction, already has yielded excellent results for a small number of aligned sequences and is suitable for large-scale genomic screens. It consists of two basic components: (i) a measure for RNA secondary structure conservation based on computing a consensus secondary structure, and (ii) a measure for thermodynamic stability, which, in the spirit of a z score, is normalized with respect to 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 www.tbi.univie.ac.at/~wash/RNAz. We screened all alignments of length n > or = 50 in the Comparative Regulatory Genomics database, which compiles conserved noncoding elements in upstream regions of orthologous genes from human, mouse, rat, Fugu, and zebrafish. We recovered all of the known noncoding RNAs and cis-acting elements with high significance and found compelling evidence for many other conserved RNA secondary structures not described so far to our knowledge.

DOI10.1073/pnas.0409169102
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID15665081
PubMed Central IDPMC548974