Computational approaches toward the design of pools for the in vitro selection of complex aptamers

Xuemei Luo, Maureen McKeague, Sylvain Pitre, Michel Dumontier, James Green, Ashkan Golshani, Maria C. Derosa*, Frank Dehne

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

40 Citations (Web of Science)

Abstract

It is well known that using random RNA/DNA sequences for SELEX experiments will generally yield low-complexity structures. Early experimental results suggest that having a structurally diverse library, which, for instance, includes high-order junctions, may prove useful in finding new functional motifs. Here, we develop two computational methods to generate sequences that exhibit higher structural complexity and can be used to increase the overall structural diversity of initial pools for in vitro selection experiments. Random Filtering selectively increases the number of five-way junctions in RNA/DNA pools, and Genetic Filtering designs RNA/DNA pools to a specified structure distribution, whether uniform or otherwise. We show that using our computationally designed DNA pool greatly improves access to highly complex sequence structures for SELEX experiments (without losing our ability to select for common one-way and two-way junction sequences).
Original languageEnglish
Pages (from-to)2252-2262
JournalRna-A Publication of the Rna Society
Volume16
Issue number11
DOIs
Publication statusPublished - Nov 2010
Externally publishedYes

Keywords

  • in vitro selection
  • random pool
  • aptamer pool design
  • RNA/DNA secondary structure
  • genetic algorithm
  • ATP aptamer

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