title: Efficient parameter estimation for RNA secondary structure prediction.
abstract: BACKGROUND
  Accurate prediction of RNA secondary structure from the base sequence is an unsolved computational challenge. The accuracy of predictions made by free energy minimization is limited by the quality of the energy parameters in the underlying free energy model. The most widely used model, the Turner99 model, has hundreds of parameters, and so a robust parameter estimation scheme should efficiently handle large data sets with thousands of structures. Moreover, the estimation scheme should also be trained using available experimental free energy data in addition to structural data.
  
  
  RESULTS
  In this work, we present constraint generation (CG), the first computational approach to RNA free energy parameter estimation that can be efficiently trained on large sets of structural as well as thermodynamic data. Our CG approach employs a novel iterative scheme, whereby the energy values are first computed as the solution to a constrained optimization problem. Then the newly computed energy parameters are used to update the constraints on the optimization function, so as to better optimize the energy parameters in the next iteration. Using our method on biologically sound data, we obtain revised parameters for the Turner99 energy model. We show that by using our new parameters, we obtain significant improvements in prediction accuracy over current state of-the-art methods.
  
  
  BACKGROUND
  Our CG implementation is available at http://www.rnasoft.ca/CG/.
authors.affiliation: Department of Computer Science, University of British Columbia, Vancouver BC V6T 1Z4, Canada. andrones@cs.ubc.ca
authors.forename: Mirela
authors.initials: M
authors.lastname: Andronescu
authors.forename: Anne
authors.initials: A
authors.lastname: Condon
authors.forename: Holger H
authors.initials: HH
authors.lastname: Hoos
authors.forename: David H
authors.initials: DH
authors.lastname: Mathews
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Murphy
mesh_terms: D000465:Algorithms; D001483:Base Sequence; D003198:Computer Simulation; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D012313:RNA / Q000737:chemistry* / Q000648:ultrastructure*; D017423:Sequence Analysis, RNA / Q000379:methods*
chemical_list: D012313:RNA