Book of Abstracts: Albany 2009

category image Albany 2009
Conversation 16
June 16-20 2009
© Adenine Press (2008)

RNA Sequence Design by Reconstruction from Shape and Guiding Observables

The process of designing novel RNA sequences by inverse RNA folding, as implemented in RNAinverse1, can be thought of as a reconstruction of RNA sequences from secondary structure. To link between the inverse RNA folding problem and physical and evolutionary perspectives2, taking into consideration possible observables such as thermodynamic stability, mutational robustness, and linguistic complexity as constraints, an extension of the reconstruction problem was suggested in3 by which the starting point is an RNA shape. Such an extension is justified, for example, in cases where a functional stem-loop structure of a natural sequence should be strictly kept in the designed sequences but a distant motif in the rest of the structure may contain one more or less nucleotide at the expense of another as long as the global shape is preserved. This allows the insertion of physical observables as constraints to the problem, in addition to local sequence and structure rigid ones. In3, the problem was solved by a parallel evolutionary algorithm without considering computational cost. In practice, an efficient method should be developed for a uniprocessor server that solves this problem using an RNAinverse-like approach.

A.A. is partially supported by the Lynn and William Frankel Center for Computer Sciences at Ben-Gurion University.

References and Footnotes
  1. I.L. Hofacker, W. Fontana, P.F. Stadler, L.S. Bonhoeffer, M. Tacker, P. Schuster (1994): "Fast Folding and Comparison of RNA Secondary Structures", Monatsh. Chem., 125:167?188.
  2. P.G. Higgs (2000): "RNA Secondary Structure: Physical and Computational Aspects", Quarterly Review of Biophysics, 33(3): 199-253.
  3. N. Dromi, A. Avihoo, D. Barash (2008): "Reconstruction of Natural RNA Sequences from RNA Shape, Thermodynamic Stability, Mutational Robustness, and Linguistic Complexity by Evolutionary Computation", Journal of Biomolecular Structure and Dynamics, 26(1):147-162.

Assaf Avihoo1
Nir Dromi2
Danny Barash1,*

1Department of Computer Science
Ben-Gurion University
Beer-Sheva 84105, Israel
2Rosetta Genomics
Weizmann Science Park
Rehovot 76706, Israel