From knotted to nested RNA structures: A variety of computational methods for pseudoknot removal

  1. Sandra Smit1,2,
  2. Kristian Rother3,
  3. Jaap Heringa1, and
  4. Rob Knight4
  1. 1Centre for Integrative Bioinformatics VU (IBIVU), Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands
  2. 2Centre for Medical Systems Biology, 2300 RA Leiden, The Netherlands
  3. 3Laboratory of Bioinformatics and Protein Engineering, International Institute of Molecular and Cell Biology, 02-109 Warsaw, Poland
  4. 4Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309, USA

Abstract

Pseudoknots are abundant in RNA structures. Many computational analyses require pseudoknot-free structures, which means that some of the base pairs in the knotted structure must be disregarded to obtain a nested structure. There is a surprising diversity of methods to perform this pseudoknot removal task, but these methods are often poorly described and studies can therefore be difficult to reproduce (in part, because different procedures may be intuitively obvious to different investigators). Here we provide a variety of algorithms for pseudoknot removal, some of which can incorporate sequence or alignment information in the removal process. We demonstrate that different methods lead to different results, which might affect structure-based analyses. This work thus provides a starting point for discussion of the extent to which these different methods recapture the underlying biological reality. We provide access to reference implementations through a web interface (at http://www.ibi.vu.nl/programs/k2nwww), and the source code is available in the PyCogent project.

Keywords

Footnotes

  • Reprint requests to: Rob Knight, Department of Chemistry and Biochemistry, Campus Box 215, University of Colorado, Boulder, CO 80309, USA; e-mail: rob{at}spot.colorado.edu; fax: (303) 492-7744.

  • Article published online ahead of print. Article and publication date are at http://www.rnajournal.org/cgi/doi/10.1261/rna.881308.

    • Received October 18, 2007.
    • Accepted December 8, 2007.
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