Thermodynamic matchers: strengthening the significance of RNA folding energies.

Thermodynamic RNA secondary structure prediction is an important recipe for the latest generation of functional non-coding RNA finding tools. However, the predicted energy is not strong enough by itself to distinguish a single functional non-coding RNA from other RNA. Here, we analyze how well an RNA molecule folds into a particular structural class with a restricted folding algorithm called Thermodynamic Matcher (TDM). We compare this energy value to that of randomized sequences. We construct and apply TDMs for the non-coding RNA families RNA I and hammerhead ribozyme type III and our results show that using TDMs rather than universal minimum free energy folding allows for highly significant predictions.

[1]  Robert Giegerich,et al.  A discipline of dynamic programming over sequence data , 2004, Sci. Comput. Program..

[2]  Robert Giegerich,et al.  Versatile and declarative dynamic programming using pair algebras , 2005, BMC Bioinformatics.

[3]  David W. Digby,et al.  mRNAs have greater negative folding free energies than shuffled or codon choice randomized sequences. , 1999, Nucleic acids research.

[4]  Peter F Stadler,et al.  Fast and reliable prediction of noncoding RNAs , 2005, Proc. Natl. Acad. Sci. USA.

[5]  I. Hofacker,et al.  Consensus folding of aligned sequences as a new measure for the detection of functional RNAs by comparative genomics. , 2004, Journal of molecular biology.

[6]  Sean R. Eddy,et al.  Rfam: annotating non-coding RNAs in complete genomes , 2004, Nucleic Acids Res..

[7]  Sean R. Eddy,et al.  Rfam: an RNA family database , 2003, Nucleic Acids Res..

[8]  Peter F. Stadler,et al.  Alignment of RNA base pairing probability matrices , 2004, Bioinform..

[9]  D. Ecker,et al.  RNAMotif, an RNA secondary structure definition and search algorithm. , 2001, Nucleic acids research.

[10]  Robert Giegerich,et al.  Abstract shapes of RNA. , 2004, Nucleic acids research.

[11]  Elena Rivas,et al.  Noncoding RNA gene detection using comparative sequence analysis , 2001, BMC Bioinformatics.

[12]  R. Giegerich,et al.  Complete probabilistic analysis of RNA shapes , 2006, BMC Biology.

[13]  T. Pollard,et al.  Annual review of biophysics and biophysical chemistry , 1985 .

[14]  D. Turner,et al.  RNA structure prediction. , 1988, Annual review of biophysics and biophysical chemistry.

[15]  Elena Rivas,et al.  Secondary structure alone is generally not statistically significant for the detection of noncoding RNAs , 2000, Bioinform..

[16]  A. Krogh,et al.  No evidence that mRNAs have lower folding free energies than random sequences with the same dinucleotide distribution. , 1999, Nucleic acids research.

[17]  Sonja J. Prohaska,et al.  Evolutionary patterns of non-coding RNAs , 2005, Theory in Biosciences.

[18]  Robert Giegerich,et al.  Consensus shapes: an alternative to the Sankoff algorithm for RNA consensus structure prediction , 2005, Bioinform..

[19]  S. Eddy.  Non–coding RNA genes and the modern RNA world , 2001, Nature Reviews Genetics.

[20]  Robert Giegerich,et al.  Design, implementation and evaluation of a practical pseudoknot folding algorithm based on thermodynamics , 2004, BMC Bioinformatics.

[21]  Jih-Hsiang Chen,et al.  Discovering well-ordered folding patterns in nucleotide sequences , 2003, Bioinform..

[22]  Michael Zuker,et al.  Mfold web server for nucleic acid folding and hybridization prediction , 2003, Nucleic Acids Res..

[23]  P. Clote,et al.  Structural RNA has lower folding energy than random RNA of the same dinucleotide frequency. , 2005, RNA.

[24]  Ivo L. Hofacker,et al.  Vienna RNA secondary structure server , 2003, Nucleic Acids Res..