Border length minimization in dna array design

Abstract

Optimal design of DNA arrays for very large-scale immobilized polymer synthesis (VLSIPS) [3] seeks to minimize effects of unintended illumination during mask exposure steps. Hannenhalli et al. [6] formulate this requirement as the Border Minimization Problem and give an algorithm for placement of probes at array sites under the assumption that the array synthesis is synchronous, i.e., nucleotides are synthesized in a periodic sequence (ACGT)k and every probe grows by exactly one nucleotide with every group of four masks. Their method reduces the number of conflicts, i.e., total mask border length, by 20-30% versus the previous standard method for array design. In this paper, we propose a probe placement algorithm for synchronous array synthesis which reduces the number of conflicts by up to 10% versus the method of Hannenhalli et al [6]. We also consider the case of asynchronous array synthesis, and present new heuristics that reduce the number of conflicts by up to a further 15.5-21.8%. Finally, we give lower bounds that offer insights into the amount of available further improvements. The paper concludes with several directions for future research.