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Sequencing DNA molecules from mechanical opening experiments: bounds from information theory and inference algorithms

Objective

The DNA molecule encodes the genetic information; reading the sequence it carries is of great relevance for biology and medicine. Currently available techniques are able to sequence DNA with high reliability but are very expensive in terms of time and human resources. We will focus on a new method for sequencing that is under intensive experimental investigation. The double helix of the DNA molecule is opened through a mechanical separation of the two strands, and the required force is measured. From the force signal one would like to reconstruct the DNA sequence.

The method is fast, but the force signal is very noisy and the reconstruction of the sequence turns out to be a difficult inference problem. A detailed comprehension of the noise and the design of optimal algorithms for data analysis are mandatory to achieve a reliable sequencing. The project will focus on the theoretical aspects of the method.

We will:
1) investigate the different sources of noise in the context of recent models for the DNA opening;
2) try to obtain theoretical bounds on the amount of information that can be obtained from the mechanical opening experiment as a function of the experimental parameters (resolution, total duration of the experiment, ...);
3) design efficient algorithms to optimise the data analysis in order to get as close as possible to the theoretical bounds;
4) test the algorithms against experimental data on known sequences and attempt to predict unknown sequences.

The project, if successful, will clearly establish the intrinsic limits of the method, in terms of information theory. Our results will be validated through a close collaboration with a leading experimental group in the field and, hopefully, will allow for a reliable mechanical sequencing in a not too far future. We believe that the project will enhance the EU competitivity in the thematic priorities 3 (nanosciences) and 1 (genomics) of the FP6.

Coordinator

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE

Address

3 Rue Michel-Ange
Paris

France

Project information

Grant agreement ID: 38751

  • Start date

    1 October 2007

  • End date

    31 January 2009

Funded under:

FP6-MOBILITY

Coordinated by:

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE

France