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Open Access Highly Accessed Methodology article

RNAspa: a shortest path approach for comparative prediction of the secondary structure of ncRNA molecules

Yair Horesh1, Tirza Doniger2, Shulamit Michaeli2 and Ron Unger2*

Author Affiliations

1 Department of Computer Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel

2 The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel

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BMC Bioinformatics 2007, 8:366  doi:10.1186/1471-2105-8-366

Published: 1 October 2007

Abstract

Background

In recent years, RNA molecules that are not translated into proteins (ncRNAs) have drawn a great deal of attention, as they were shown to be involved in many cellular functions. One of the most important computational problems regarding ncRNA is to predict the secondary structure of a molecule from its sequence. In particular, we attempted to predict the secondary structure for a set of unaligned ncRNA molecules that are taken from the same family, and thus presumably have a similar structure.

Results

We developed the RNAspa program, which comparatively predicts the secondary structure for a set of ncRNA molecules in linear time in the number of molecules. We observed that in a list of several hundred suboptimal minimal free energy (MFE) predictions, as provided by the RNAsubopt program of the Vienna package, it is likely that at least one suggested structure would be similar to the true, correct one. The suboptimal solutions of each molecule are represented as a layer of vertices in a graph. The shortest path in this graph is the basis for structural predictions for the molecule. We also show that RNA secondary structures can be compared very rapidly by a simple string Edit-Distance algorithm with a minimal loss of accuracy. We show that this approach allows us to more deeply explore the suboptimal structure space.

Conclusion

The algorithm was tested on three datasets which include several ncRNA families taken from the Rfam database. These datasets allowed for comparison of the algorithm with other methods. In these tests, RNAspa performed better than four other programs.