Adam Nilsson
Theoretical calculations for competitive binding of site-specific-mers: Joint theory-experimental study of nanochannel-based optical DNA maps

Master Thesis in Theoretical Physics

Abstract: A new experimental method in our collaborators labs provides a coarse-grained map of the DNA sequence of a microorganism using two substances netropsin and YOYO-1. Netropsin binds differently to different base pair regions and YOYO-1 is nonselective to base pairs regions but fluorescent. Together in a solution they will compete for binding to the DNA and will provide a barcode pattern that is representative of the DNA sequence of the molecule studied. In this thesis theoretical barcodes are calculated using the transfer matrix approach to be able to strengthen the theory behind the experiment and in the future be able to create a vast database of theoretical barcodes for DNA sequences from known microorganisms. If an experiment is performed on DNA from an unknown microorganism this database could be used to determine the microorganism by comparing the experimental and theoretical barcodes. The experiments results in kymographs (time-frames of fluorescent images of DNA stretched using nanochannels) that are aligned using a method adapted from "Denaturation mapping of Saccharomyces cerevisiae" pages 3314-3321, Lab Chip, Walter W. Reisner, to take care of center of mass and conformational fluctuations of the DNA between frames in the kymograph so that the frames can be averaged in a good way. A new two-dimensional dynamic time warping was developed by the author to allow the theoretical barcode to account for the fluctuations in the experimental barcode. An information measure was also developed that is higher the more peaks and valleys there are a in a barcode and the more separated these peaks and valleys are in intensity compared to the noise of the barcode. A graphical Java-program was developed to help the experimentalists get the most out of their experiments and to be able to compare the experimental and theoretical barcodes.


LU TP 12-XX