Tuesday, January 28, 2014

Reconstruction and Identification of DNA Sequence Landscapes from Unzipping Experiments at Equilibrium

Carlo Barbieri, Simona Cocco, Thomas Jorg, Rémi Monasson

Two methods for reconstructing the free-energy landscape of a DNA molecule from the knowledge of the equilibrium unzipping force versus extension signal are introduced: a simple and fast procedure, based on a parametric representation of the experimental force signal, and a maximum-likelihood inference of coarse-grained free-energy parameters. In addition, we propose a force alignment procedure to correct for the drift in the experimental measure of the opening position, a major source of error. For unzipping data obtained by Huguet et al., the reconstructed basepair (bp) free energies agree with the running average of the true free energies on a 20–50 bp scale, depending on the region in the sequence. Features of the landscape at a smaller scale (5–10 bp) could be recovered in favorable regions at the beginning of the molecule. Based on the analysis of synthetic data corresponding to the 16S rDNA gene of bacteria, we show that our approach could be used to identify specific DNA sequences among thousands of homologous sequences in a database.

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