title: Secondary structure alone is generally not statistically significant for the detection of noncoding RNAs.
abstract: BACKGROUND
  Several results in the literature suggest that biologically interesting RNAs have secondary structures that are more stable than expected by chance. Based on these observations, we developed a scanning algorithm for detecting noncoding RNA genes in genome sequences, using a fully probabilistic version of the Zuker minimum-energy folding algorithm.
  
  
  RESULTS
  Preliminary results were encouraging, but certain anomalies led us to do a carefully controlled investigation of this class of methods. Ultimately, our results argue that for the probabilistic model there is indeed a statistical effect, but it comes mostly from local base-composition bias and not from RNA secondary structure. For the thermodynamic implementation (which evaluates statistical significance by doing Monte Carlo shuffling in fixed-length sequence windows, thus eliminating the base-composition effect) the signals for noncoding RNAs are still usually indistinguishable from noise, especially when certain statistical artifacts resulting from local base-composition inhomogeneity are taken into account. We conclude that although a distinct, stable secondary structure is undoubtedly important in most noncoding RNAs, the stability of most noncoding RNA secondary structures is not sufficiently different from the predicted stability of a random sequence to be useful as a general genefinding approach.
authors.affiliation: Department of Genetics, Washington University, St. Louis, MO 63110, USA.
authors.forename: E
authors.initials: E
authors.lastname: Rivas
authors.forename: S R
authors.initials: SR
authors.lastname: Eddy
mesh_terms: D000465:Algorithms; D000818:Animals; D001482:Base Composition; D017173:Caenorhabditis elegans / Q000235:genetics; D003627:Data Interpretation, Statistical; D017017:Methanococcus / Q000235:genetics; D015233:Models, Statistical; D009690:Nucleic Acid Conformation; D012313:RNA / Q000737:chemistry*; D018510:RNA, Helminth / Q000032:analysis
chemical_list: D018510:RNA, Helminth; D012313:RNA