title: Quantifying variances in comparative RNA secondary structure prediction.
abstract: BACKGROUND
  With the advancement of next-generation sequencing and transcriptomics technologies, regulatory effects involving RNA, in particular RNA structural changes are being detected. These results often rely on RNA secondary structure predictions. However, current approaches to RNA secondary structure modelling produce predictions with a high variance in predictive accuracy, and we have little quantifiable knowledge about the reasons for these variances.
  
  
  RESULTS
  In this paper we explore a number of factors which can contribute to poor RNA secondary structure prediction quality. We establish a quantified relationship between alignment quality and loss of accuracy. Furthermore, we define two new measures to quantify uncertainty in alignment-based structure predictions. One of the measures improves on the "reliability score" reported by PPfold, and considers alignment uncertainty as well as base-pair probabilities. The other measure considers the information entropy for SCFGs over a space of input alignments.
  
  
  CONCLUSIONS
  Our predictive accuracy improves on the PPfold reliability score. We can successfully characterize many of the underlying reasons for and variances in poor prediction. However, there is still variability unaccounted for, which we therefore suggest comes from the RNA secondary structure predictive model itself.
authors: Department of Statistics, South Parks Road, Oxford, UK. anderson@stats.ox.ac.uk
authors: James W J
authors: JW
authors: Anderson
authors: Ádám
authors: Á
authors: Novák
authors: Zsuzsanna
authors: Z
authors: Sükösd
authors: Michael
authors: M
authors: Golden
authors: Preeti
authors: P
authors: Arunapuram
authors: Ingolfur
authors: I
authors: Edvardsson
authors: Jotun
authors: J
authors: Hein
mesh_terms: D000465:Algorithms; D020029:Base Pairing; D019143:Evolution, Molecular; D009690:Nucleic Acid Conformation; D011336:Probability; D012313:RNA / Q000737:chemistry*; D015203:Reproducibility of Results; D016415:Sequence Alignment / Q000379:methods* / Q000592:standards; D017423:Sequence Analysis, RNA
chemical_list: D012313:RNA
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