Using an RNA secondary structure partition function to determine confidence in base pairs predicted by free energy minimization.
A partition function calculation for RNA secondary structure is presented that uses a current set of nearest neighbor parameters for conformational free energy at 37 degrees C, including coaxial stacking. For a diverse database of RNA sequences, base pairs in the predicted minimum free energy structure that are predicted by the partition function to have high base pairing probability have a significantly higher positive predictive value for known base pairs. For example, the average positive predictive value, 65.8%, is increased to 91.0% when only base pairs with probability of 0.99 or above are considered. The quality of base pair predictions can also be increased by the addition of experimentally determined constraints, including enzymatic cleavage, flavin mono-nucleotide cleavage, and chemical modification. Predicted secondary structures can be color annotated to demonstrate pairs with high probability that are therefore well determined as compared to base pairs with lower probability of pairing.
Center for Human Genetics and Molecular Pediatric Disease, Aab Institute of Biomedical Sciences, University of Rochester Medical Center, 601 Elmwood Avenue, Box 703, NY 14642, USA. David_Mathews@urmc.rochester.edu
David H
DH
Mathews
D000465:Algorithms; D000818:Animals; D019295:Computational Biology / Q000379:methods*; D003627:Data Interpretation, Statistical; D006801:Humans; D009690:Nucleic Acid Conformation; D017423:Sequence Analysis, RNA