Abstract
Many biologically important RNA structures are conserved in evolution leading to characteristic mutational patterns. RNAalifold is a widely used program to predict consensus secondary structures in multiple alignments by combining evolutionary information with traditional energy-based RNA folding algorithms. Here we describe the theory and applications of the RNAalifold algorithm. Consensus secondary structure prediction not only leads to significantly more accurate structure models, but it also allows to study structural conservation of functional RNAs.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Washietl S, Pedersen JS, Korbel JO, Stocsits C, Gruber AR, Hackermüller J, Hertel J, Lindemeyer M, Reiche K, Tanzer A, Ucla C, Wyss C, Antonarakis SE, Denoeud F, Lagarde J, Drenkow J, Kapranov P, Gingeras TR, Guigó R, Snyder M, Gerstein MB, Reymond A, Hofacker IL, Stadler PF (2007) Structured RNAs in the ENCODE selected regions of the human genome. Genome Res 17: 852–864. doi:10.1101/gr.5650707
Gardner PP, Giegerich R (2004) A comprehensive comparison of comparative RNA structure prediction approaches. BMC Bioinformatics 5: 140. doi:10.1186/1471-2105-5-140
Gardner PP, Wilm A, Washietl S (2005) A benchmark of multiple sequence alignment programs upon structural RNAs. Nucleic Acids Res 33: 2433–2439. doi:10.1093/nar/gki541
Wilm A, Mainz I, Steger G (2006) An enhanced RNA alignment benchmark for sequence alignment programs. Algorithms Mol Biol 1: 19. doi:10.1186/1748-7188-1-19
Höchsmann M, Voss B, Giegerich R (2004) Pure multiple RNA secondary structure alignments: a progressive profile approach. IEEE/ACM Trans Comput Biol Bioinform 1: 53–62. doi:10.1109/TCBB.2004.11
Sankoff D (1985) Simultaneous solution of the RNA folding, alignment and protosequence problems. SIAM J Appl Math 45: 810–825
Noller HF, Kop J, Wheaton V, Brosius J, Gutell RR, Kopylov AM, Dohme F, Herr W, Stahl DA, Gupta R, Woese CR (1981) Secondary structure model for 23s ribosomal RNA. Nucleic Acids Res 9 (22): 6167–6189. doi:10.1093/nar/9.22.6167
Hofacker IL, Fekete M, Stadler PF (2002) Secondary structure prediction for aligned RNA sequences. J Mol Biol 319: 1059–1066. doi:10.1016/S0022-2836(02)00308-X
Zuker M, Stiegler P (1981) Optimal computer folding of large RNA sequences using thermodynamics and auxiliary information. Nucleic Acids Res 9: 133–148.
Bernhart SH, Hofacker IL, Will S, Gruber AR, Stadler PF (2008) RNAalifold: improved consensus structure prediction for RNA alignments. BMC Bioinformatics 9: 474. doi:10.1186/1471-2105-9-474
Klein RJ, Eddy SR (2003) RSEARCH: finding homologs of single structured RNA sequences. BMC Bioinformatics 4: 44. doi:10.1186/1471-2105-4-44
McCaskill JS (1990) The equilibrium partition function and base pair binding probabilities for RNA secondary structure. Biopolymers 29: 1105–1119. doi:10.1002/bip.360290621
Ding Y, Lawrence CE (1999) A bayesian statistical algorithm for RNA secondary structure prediction. Comput Chem 23 (3–4): 387–400.
Ding Y, Chan CY, Lawrence CE (2005) RNA secondary structure prediction by centroids in a boltzmann weighted ensemble. RNA 11 (8): 1157–1166. doi:10.1261/rna.2500605
Hofacker IL, Priwitzer B, Stadler PF (2004) Prediction of locally stable RNA secondary structures for genome-wide surveys. Bioinformatics 20: 186–190. doi:10.1093/bioinformatics/btg388
Washietl S, Hofacker IL (2004) Consensus folding of aligned sequences as a new measure for the detection of functional RNAs by comparative genomics. J Mol Biol 342: 19–30. doi:10.1016/j.jmb.2004.07.018
Gruber AR, Bernhart SH, Hofacker IL, Washietl S (2008) Strategies for measuring evolutionary conservation of RNA secondary structures. BMC Bioinformatics 9: 122. doi:10.1186/1471-2105-9-122
Gesell T, Washietl S (2008) Dinucleotide controlled null models for comparative RNA gene prediction. BMC Bioinformatics 9: 248. doi:10.1186/1471-2105-9-248
Gruber AR, Findeiß S, Washietl S, Hofacker IL, Stadler PF (2010) RNAz 2.0: improved noncoding RNA detection. Pac Symp Biocomput 15: 69–79
Washietl S (2007) Prediction of structural noncoding RNAs with RNAz. Methods Mol Biol 395: 503–526
Knudsen B, Hein J (2003) Pfold: RNA secondary structure prediction using stochastic context-free grammars. Nucleic Acids Res 31: 3423–3428
Seemann SE, Gorodkin J, Backofen R (2008) Unifying evolutionary and thermodynamic information for RNA folding of multiple alignments. Nucleic Acids Res 36: 6355–6362. doi:10.1093/nar/gkn544
Do CB, Woods DA, Batzoglou S (2006) CONTRAfold: RNA secondary structure prediction without physics-based models. Bioinformatics 22: e90–e98. doi:10.1093/ bioinformatics/btl246
Lu ZJ, Gloor JW, Mathews DH (2009) Improved RNA secondary structure prediction by maximizing expected pair accuracy. RNA 15: 1805–1813. doi:10.1261/rna.1643609
Kiryu H, Kin T, Asai K (2007) Robust prediction of consensus secondary structures using averaged base pairing probability matrices. Bioinformatics 23: 434–441. doi:10.1093/bioinformatics/btl636
Hamada M, Kiryu H, Sato K, Mituyama T, Asai K (2009) Prediction of RNA secondary structure using generalized centroid estimators. Bioinformatics 25: 465–473. doi:10.1093/bioinformatics/btn601
Hamada M, Sato K, Asai K (2011) Improving the accuracy of predicting secondary structure for aligned RNA sequences. Nucleic Acids Res 39: 393–402. doi:10.1093/ nar/ gkq792
Edgar RC (2004) MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res 32: 1792–1797. doi:10.1093/nar/gkh340
Acknowledgements
Stefan Washietl was supported by an Erwin Schrödinger Fellowship of the Austrian Fonds zur Förderung der Wissenschaftlichen Forschung. Stephan H. Bernhart was funded by the Austrian GEN-AU project “Noncoding RNA.” We thank Ivo Hofacker and Benjamin Holmes for comments on the manuscript.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer Science+Business Media New York
About this protocol
Cite this protocol
Washietl, S., Bernhart, S.H., Kellis, M. (2014). Energy-Based RNA Consensus Secondary Structure Prediction in Multiple Sequence Alignments. In: Gorodkin, J., Ruzzo, W. (eds) RNA Sequence, Structure, and Function: Computational and Bioinformatic Methods. Methods in Molecular Biology, vol 1097. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-709-9_7
Download citation
DOI: https://doi.org/10.1007/978-1-62703-709-9_7
Published:
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-62703-708-2
Online ISBN: 978-1-62703-709-9
eBook Packages: Springer Protocols