CPSC 536A Course Project
Spring 2001
| Tim Braun | tbraun@cs.ubc.ca |
| James Gauthier | gauthier@cs.ubc.ca |
| Tam Huynh | tam@juggler.net |
| Louie van de Lagemaat | lvandela@terryfox.ubc.ca |
Introduction
An important task in biotechnology is to analyze a mixture of DNA strands in order to investigate certain properties of their structure and composition. In most cases, such a mixture may contain thousands of types of DNA strands. Therefore, DNA strand analysis requires fast, yet reliable, methods to probe the strands. One technique is known as array-based hybridization assay. Conventional array-based hybridization assays involve probing DNA in solution with probes attached to a chip in a regular rectangular array.
To address the need for a multitude of different arrays, Ben-Dor, et. al. discuss a universal Tag/AntiTag (TAT) system. In this system, the probe for a given gene or DNA strand of interest is ligated to a tag, the antitag for which has been synthesized on the array. This tag/probe construct is used as a reporter molecule. Thus, in practice, an experiment consists of two steps. In the first (solution-phase) step, mixed single-stranded DNAs of interest hybridize to reporter molecules. In the second step, the reporter/sample pairs are washed over the array and attach to their respective antitags. Fluorescent markers attached to the DNAs of interest give a measurable signal.
Theoretically, DNA tags should match only to their antitags. Thus, to avoid spurious cross-hybridization, tag/antitag pairs must be distinct. This problem presents an interesting challenge. Ben-Dor, et. al. present a combinatorial solution to this challenge. This solution involves a simplistic computation of a melting pseudo-temperature for each tag/antitag pair based on base-pairing. The melting temperature is calculated as two points for each CG base pair and one point for each AT pair (this is known as the 2-4 rule). Combinations of tags are limited by eliminating cross-hybridizations of melting temperature higher than C, a ``cool'' temperature, and only allowing true hybridizations of melting temperature higher than H, a ``hotter'' temperature.
Our goal with this project is to implement an algorithm similar to the
one presented by Ben-Dor, et. al. However, we would like to
use a more sophisticated estimate of melting temperature than the simplistic
2-4 rule. Research has led us to consider the Nearest Neighbour Model
as an estimate of melting temperature.
Contents
Updated April 4, 2001