DOI: 10.1073/pnas.0409169102. Fast and reliable prediction of noncoding RNAs

Fast and reliable prediction of noncoding RNAs

10.1073/pnas.0409169102

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

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 ≥ 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.

Bibliography

Washietl, S., Hofacker, I. L., & Stadler, P. F. (2005). Fast and reliable prediction of noncoding RNAs. Proceedings of the National Academy of Sciences, 102(7), 2454â2459.

Authors 3

Stefan Washietl (first)
Ivo L. Hofacker (additional)
Peter F. Stadler (additional)

References 47 Referenced 529

10.1038/35103511
10.1126/science.1072249
10.1002/bies.10332
10.1038/nrg1379
10.1038/35047580
10.1002/bies.20084
10.1016/S0092-8674(04)00127-8
10.1101/gr.2094104
10.1016/j.tibs.2003.11.004
10.1093/nar/28.24.4974
10.1093/nar/gkg551
10.1038/nature01644
10.1126/science.282.5396.2012
10.1371/journal.pbio.0000045
10.1038/35057062
10.1038/nature01262
10.1038/nature02426
10.1126/science.1098119
10.1093/bioinformatics/bth946
10.1038/nature01858
10.1101/gr.1602203
10.1186/1471-2105-2-8
10.1016/S0960-9822(01)00401-8
10.1093/nar/gkg438
10.1093/bioinformatics/btg229
10.1073/pnas.0404193101
10.1007/BF00818163
10.1016/S0022-2836(02)00308-X
10.1101/gr.1933104
10.1093/nar/27.24.4816
10.1093/nar/gkg006
10.1093/nar/gkg107
10.1093/nar/27.1.314
10.1016/j.jmb.2004.07.018
10.1093/nar/9.1.133
10.1073/pnas.91.20.9218
10.1006/jmbi.1999.2700
10.1093/bioinformatics/16.7.583
10.1093/bioinformatics/bth374
Le, S. V., Chen, J. H., Currey, K. M. & Maizel, J. V., Jr. (1988) Comput. Appl. Biosci. 4, 153-159.2454711 / Comput. Appl. Biosci. (1988)
Cristianini N. & Shawe-Taylor J. (2000) An Introduction to Support Vector Machines (Cambridge Univ. Press Cambridge U.K.).
10.1093/nar/gkg007
Griffiths-Jones, S. (2004) Nucleic Acids Res. 32, D109-D111.14681370 (10.1093/nar/gkh023) / Nucleic Acids Res. (2004)
10.1093/nar/30.1.335
10.1093/nar/25.2.362
10.1073/pnas.93.16.8175
10.1101/gr.229102

Dates

Type	When
Created	20 years, 7 months ago (Jan. 21, 2005, 8:41 p.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 2:30 p.m.)
Indexed	1 day, 8 hours ago (Aug. 31, 2025, 7:15 p.m.)
Issued	20 years, 7 months ago (Jan. 21, 2005)
Published	20 years, 7 months ago (Jan. 21, 2005)
Published Online	20 years, 7 months ago (Jan. 21, 2005)
Published Print	20 years, 6 months ago (Feb. 15, 2005)

Funders 0

None

BibTeX

@article{Washietl_2005, title={Fast and reliable prediction of noncoding RNAs}, volume={102}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.0409169102}, DOI={10.1073/pnas.0409169102}, number={7}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Washietl, Stefan and Hofacker, Ivo L. and Stadler, Peter F.}, year={2005}, month=jan, pages={2454–2459} }

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