RNA Secondary Structure Analysis Using The RNAshapes Package

Jens Reeder1, Robert Giegerich2

1 University of Colorado, Boulder, Colorado, 2 Bielefeld University, Bielefeld, Germany
Publication Name:  Current Protocols in Bioinformatics
Unit Number:  Unit 12.8
DOI:  10.1002/0471250953.bi1208s26
Online Posting Date:  June, 2009
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This unit shows how to use the RNAshapes package for the prediction of the secondary structure of a single RNA sequence using either minimum free energy methods or weighted ensemble information. It also includes a protocol for the consensus prediction of a set of related sequences. Curr. Protoc. Bioinform. 26:12.8.1‐12.8.17. © 2009 by John Wiley & Sons, Inc.

Keywords: RNA secondary structure; minimum free energy; Boltzmann weighted ensemble; consensus structure; software package; suboptimal folding space; graphical user interface

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Table of Contents

  • Introduction
  • Basic Explanations
  • Basic Protocol 1: Minimum Free Energy Prediction of Shape Representative Structures
  • Basic Protocol 2: Probabilistic Shape Analysis
  • Basic Protocol 3: Comparative Shapes Analysis
  • Support Protocol 1: Installation of the RNAshapes Package
  • Commentary
  • Literature Cited
  • Figures
  • Tables
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Literature Cited

   Berezikov, E., van Tetering, G., Verheul, M., van de Belt, J., van Laake, L., Vos, J., Verloop, R., van de Wetering, M., Guryev, V., Takada, S., van Zonneveld, A.J., Mano, H., Plasterk, R., and Cuppen, E. 2006. Many novel mammalian microRNA candidates identified by extensive cloning and RAKE analysis. Genome Res. 16:1289‐1298.
   Ding, Y. and Lawrence, C.E. 2003. A statistical sampling algorithm for RNA secondary structure prediction. Nucleic Acids Res. 31:7280‐7301.
   Doshi, K., Cannone, J., Cobaugh, C., and Gutell, R. 2004. Evaluation of the suitability of free‐energy minimization using nearest‐neighbor energy parameters for RNA secondary structure prediction. BMC Bioinformatics 5:105
   Flamm, C., Hofacker, I.L., Stadler, P.F., and Wolfinger, M.T. 2002. Barrier trees of degenerate landscapes. Z. Phys. Chem. 216:1‐19.
   Gardner, P.P. and Giegerich, R. 2004. A comprehensive comparison of comparative RNA structure prediction approaches. BMC Bioinformatics 5:140.
   Giegerich, R., Haase, D., and Rehmsmeier, M. 1999. Prediction and visualization of structural switches in RNA. In Proceedings of the 1999 Pacific Symposium on Biocomputing 4:126‐137. World Scientific Publishing, Singapore.
   Giegerich, R., Voss, B., and Rehmsmeier, M. 2004. Abstract shapes of RNA. Nucleic Acids Res. 32:4843‐4851.
   Höchsmann, M., Voss, B., and Giegerich, R. 2004. Pure multiple RNA secondary structure alignments: A progressive profile approach. IEEE/ACM Trans. Comput. Biol. Bioinform. 1:53‐62.
   Hofacker, I.L. 2004. RNA secondary structure analysis using the Vienna RNA package. Curr. Protoc. Bioinform. 4:12.2.1‐12.2.12
   Hofacker, I.L., Fekete, M., and Stadler, P.F. 2002. Secondary structure prediction for aligned RNA sequences. J. Mol. Biol. 319:1059‐1066.
   Hofacker, I.L., Fontana, W., Stadler, P.F., Bonhoeffer, S., Tacker, M., and Schuster, P. 1994. Fast folding and comparison of RNA secondary structures. Monatsh. Chem. 125:167‐188.
   Janssen, S., Reeder, J., and Giegerich, R. 2008. Shape based indexing for faster search of RNA family databases. BMC Bioinformatics 9:131.
   Lu, J., Shen, Y., Wu, Q., Kumar, S., He, B., Shi, S., Carthew, R.W., Wang, S.M., and Wu, C.‐I. 2008. The birth and death of microRNA genes in Drosophila. Nat. Genet. 40:351‐355.
   Mathews, D.H. 2006. RNA secondary structure analysis using RNAstructure. Curr. Protoc. Bioinform. 13:12.6.1‐12.6.14.
   Mathews, D.H., Sabina, J., Zuker, M. and Turner, D.H. 1999. Expanded sequence dependence of thermodynamic parameters improves prediction of RNA secondary structure. J. Mol. Biol. 288:911‐940.
   McCaskill, J.S. 1990. The equilibrium partition function and base pair binding probabilities for RNA secondary structure. Biopolymers 29:1105‐1119.
   Meyer, I.M. and Miklós, I. 2004. Co‐transcriptional folding is encoded within RNA genes. BMC Mol. Biol. 5:10.
   Reeder, J. and Giegerich, R. 2005. Consensus shapes: An alternative to the Sankoff algorithm for RNA consensus structure prediction. Bioinformatics 21:3516‐3523.
   Rieder, R., Lang, K., Graber, D. and Micura, R. 2007. Ligand‐induced folding of the adenosine deaminase A‐riboswitch and implications on riboswitch translational control. Chembiochem 8:896‐902.
   Stein, P.R. and Waterman, M.S. 1978. On some new sequences generalizing the Catalan and Motzkin numbers. Discr. Math. 26:261‐272.
   Torarinsson, E., Havgaard, J.H., and Gorodkin, J. 2007. Multiple structural alignment and clustering of RNA sequences. Bioinformatics 23:926‐932.
   Voss, B., Giegerich, R., and Rehmsmeier, M. 2006. Complete probabilistic analysis of RNA shapes. BMC Biol. 4:5.
   Voss, B., Meyer, C., and Giegerich, R. 2004. Evaluating the predictability of conformational switching in RNA. Bioinformatics 20:1573‐1582.
   Will, S., Reiche, K., Hofacker, I.L., Stadler, P.F., and Backofen, R. 2007. Inferring non‐coding RNA families and classes by means of genome‐scale structure‐based clustering. PLoS Comput. Biol. 3:e65
   Wuchty, S., Fontana, W., Hofacker, I.L., and Schuster, P. 1999. Complete suboptimal folding of RNA and the stability of secondary structures. Biopolymers 49:145‐165.
   Yao, Z., Weinberg, Z., and Ruzzo, W.L. 2006. CMfinder: A covariance model based RNA motif finding algorithm. Bioinformatics 22:445‐452.
   Zuker, M. 1989. On finding all suboptimal foldings of an RNA molecule. Science 244:48‐52.
   Zuker, M. 2003. Mfold web server for nucleic acid folding and hybridization prediction. Nucleic Acids Res. 31:3406‐3415.
   Zuker, M. and Stiegler, P. 1981. Optimal computer folding of large RNA sequences using thermodynamic and auxiliary information. Nucleic Acids Res. 9:133‐148.
Key References
   Giegerich et al., 2004. See above.
  Introduces the abstract shape technique into minimum free energy prediction.
   Reeder and Giegerich, 2005. See above.
  Comparative structure prediction employing abstract shapes.
   Voss et al., 2006. See above.
  Extends the shapes approach to a complete probabilistic analysis.
Internet Resources
  The project's home page where the latest distribution can be downloaded and also be used online.
  Collection of several RNA‐related tools, mostly for online use via Web interface and also for download.
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