Improved energy parameters for RNA pseudoknotted secondary structure prediction

Mirela Andronescu, Cristina Pop and Anne Condon

• Abstract. Accurate prediction of RNA pseudoknotted secondary structures from the base sequence is a challenging computational problem.  Since prediction algorithms rely on thermodynamic energy models to identify low-energy structures, prediction accuracy relies in large part on the quality of free energy change parameters.  In this work, we use our earlier Constraint Generation and Boltzmann Likelihood parameter estimation methods to obtain new energy parameters for two energy models for secondary structures with pseudoknots, namely the Dirks & Pierce (DP) and the Cao & Chen (CC) models.  To train our parameters, and also to test their accuracy, we create a large data set of both pseudoknotted and pseudoknot free secondary structures. In addition to structural data, our training data set also includes thermodynamic data, for which experimentally determined free energy changes are available for sequences and their reference structures.  When incorporated into the HotKnots prediction algorithm, our new parameters result in significantly improved secondary structure prediction, on our test dataset. Specifically, the prediction accuracy when using our new parameters improves from 68% to 79% for the DP model, and from 70% to 77% for the CC model. 

• Paper
• Parameter estimation algorithms
  • Constraint Generation v2.0
• Secondary structure prediction algorithms
  • Simfold, part of MultiRNAFold v2.0
  • Run HotKnots 2.0 online, with the new parameters
  • Download HotKnots v2.0 (includes PKEnergy)
• Data sets
  • S-Train
  • S-Train-MT
  • T-Train
  • T-Train-MT
  • S-Test: ShPK, LoPK, ShPKfree, LoPKfree
• Results

  Parameter set	Predictions on ShPK (with suboptimals)	Predictions on LoPK (with suboptimals)	Predictions on ShPKfree (with suboptimals)	Predictions on LoPKfree (with suboptimals)	Predictions on  S-Test (with suboptimals)	Energies on T-Train
  MT99
  MT09
  DP03	txt file	txt file	txt file	txt file	txt file	txt file
  DP09	txt file	txt file	txt file	txt file	txt file	txt file
  CC06	txt file	txt file	txt file	txt file	txt file	txt file
  CC09	txt file	txt file	txt file	txt file	txt file	txt file

• Configuration files
  • Configuration file to give as input to CG, to obtain DP09