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Bioinformatics 2009 25(12):i374-i1382; doi:10.1093/bioinformatics/btp210
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© 2009 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Predicting and understanding the stability of G-quadruplexes

Oliver Stegle 1,*, Linda Payet 1, Jean-Louis Mergny 2, David J. C. MacKay 1 and Julian Leon Huppert 1,*

1Cavendish Laboratory, University of Cambridge, JJ Thomson Avenue, Cambridge CB3 0HE, UK and 2Laboratoire de Biophysique, Museum National d'Histoire Naturelle USM503, INSERM U565, CNRS UMR 5153 43 Rue Cuvier, 75231 Paris Cedex 05, France

*To whom correspondence should be addressed.


  Abstract

Motivation: G-quadruplexes are stable four-stranded guanine-rich structures that can form in DNA and RNA. They are an important component of human telomeres and play a role in the regulation of transcription and translation. The biological significance of a G-quadruplex is crucially linked with its thermodynamic stability. Hence the prediction of G-quadruplex stability is of vital interest.

Results: In this article, we present a novel Bayesian prediction framework based on Gaussian process regression to determine the thermodynamic stability of previously unmeasured G-quadruplexes from the sequence information alone. We benchmark our approach on a large G-quadruplex dataset and compare our method to alternative approaches. Furthermore, we propose an active learning procedure which can be used to iteratively acquire data in an optimal fashion. Lastly, we demonstrate the usefulness of our procedure on a genome-wide study of quadruplexes in the human genome.

Availability: A data table with the training sequences is available as supplementary material. Source code is available online at http://www.inference.phy.cam.ac.uk/os252/projects/quadruplexes

Contact: os252{at}cam.ac.uk; jlh29{at}cam.ac.uk

Supplementary information: Supplementary data are available at Bioinformatics online.


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A. Guedin, P. Alberti, and J.-L. Mergny
Stability of intramolecular quadruplexes: sequence effects in the central loop
Nucleic Acids Res., September 1, 2009; 37(16): 5559 - 5567.
[Abstract] [Full Text] [PDF]


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