DNA Word Design Strategy for Creating Sets of Non-interacting Oligonucleotides for DNA Microarrays

Abstract

A template−map design strategy for generating sets of non-interacting DNA oligonucleotides for applications in DNA arrays and biosensors is demonstrated. This strategy is used to create a set of oligonucleotides of size s with length l that possess at least n base mismatches with the complements of all the other members in the set. These “DNA word” sets are denoted as nbm l-mers or l:n sets. To regularize the thermodynamic stability of the perfectly matched hybridized DNA duplexes, the l-mers chosen for all the sets are required to have an approximately 50% G/C content. To achieve good discrimination between each DNA word in each set generated using the template−map strategy, it is required that n should be approximately equal to l/2 or higher. The template−map strategy can be used in a straightforward manner to create DNA word sets for cases when l = 4k and n = 2k, where k is an integer. Specific examples of 4k:2k sets are designed: an 8:4 set (s = 224), a 12:6 set (s = 528), a 16:8 set (s = 960), and a...