ViennaRNA Package 2.0

Abstract

Background: Secondary structure forms an important intermediate level of description of nucleic acids that encapsulates the dominating part of the folding energy, is often well conserved in evolution, and is routinely used as a basis to explain experimental findings. Based on carefully measured thermodynamic parameters, exact dynamic programming algorithms can be used to compute ground states, base pairing probabilities, as well as thermodynamic properties.

Results: The ViennaRNA Package has been a widely used compilation of RNA secondary structure related computer programs for nearly two decades. Major changes in the structure of the standard energy model, the Turner 2004 parameters, the pervasive use of multi-core CPUs, and an increasing number of algorithmic variants prompted a major technical overhaul of both the underlying RNAlib and the interactive user programs. New features include an expanded repertoire of tools to assess RNA-RNA interactions and restricted ensembles of structures, additional output information such as centroid structures and maximum expected accuracy structures derived from base pairing probabilities, or z-scores for locally stable secondary structures, and support for input in fasta format. Updates were implemented without compromising the computational efficiency of the core algorithms and ensuring compatibility with earlier versions.

Conclusions: The ViennaRNA Package 2.0, supporting concurrent computations via OpenMP, can be downloaded from http://www.tbi.univie.ac.at/RNA.

Figure 1

Example calls of programs included in the ViennaRNA Package and their corresponding output. (A) Single sequence analysis using RNAfold. (B) Locally optimal secondary structures and base pair probabilities using RNAplfold and RNALfold. (C) Interaction thermodynamics of two RNA sequences computed by RNAup. (D) Consensus structures and base pair probabilities for RNA sequence alignments obtained from RNAalifold. (E) Secondary structure of an RNA dimer calculated by RNAcofold. (F) Folding kinetics using RNAsubopt in conjunction with the external programs barriers and treekin. (G) Suboptimal secondary structures generated by RNAsubopt. For a detailed description see the appendix.

Figure 2

Performance comparison of RNAfold 2.0 to other secondary structure prediction software. (A) Accuracy of thermodynamic folding programs in terms of cumulative distribution of the Matthews correlation coefficient (MCC). RNAfold 2.0 outperforms the other secondary structure prediction programs on the RNAstrand dataset: more of its predictions fall into the region of higher performance values. Both versions of RNAfold were run with -d2 option. For UNAFold and RNAStructure default options were used. Performance distributions of Sensitivity, Positive predictive value (PPV) and F-measure are shown in Additional File 1. The averaged overall accuracies can be taken from table 2. (B) Comparison of runtimes for MFE structure predictions. Measurement was performed on an Intel^® Core™ 2 6600 CPU running at 2.4 GHz. Shown are averaged running times for random sequences of lengths 100 nt (100 samples), 500 nt (100 samples), 1000 nt (100 samples), 2500 nt (20 samples), 5000 nt (16 samples) and 10000 nt (16 samples). While the compared programs RNAfold 2.0, RNAfold 1.8.5 and UNAfold 3.8 were capable of predicting an MFE structure for all tested samples in a relatively small time frame, RNAstructure 5.2 was omitted from predictions for the 10000 nt sample set due to its time requirements.