Improved Tag Set Design and Multiplexing Algorithms for Universal Arrays.pdf

a r X i v : c s / 0 5 0 2 0 5 4 v 1 [ c s .D S ] 1 0 F e b 2 0 0 5 Improved Tag Set Design and Multiplexing Algorithms for Universal Arrays? Ion I. Ma?ndoiu, Claudia Pra?jescu, and Dragos? Trinca? CSE Department, University of Connecticut 371 Fairfield Rd., Unit 2155, Storrs, CT 06269-2155 {ion.mandoiu,claudia.prajescu,dragos.trinca}@ Abstract. In this paper we address two optimization problems arising in the design of genomic assays based on universal tag arrays. First, we address the universal array tag set design problem. For this problem, we extend previous formulations to incorporate antitag-to-antitag hybridiza- tion constraints in addition to constraints on antitag-to-tag hybridization specificity, establish a constructive upper bound on the maximum num- ber of tags satisfying the extended constraints, and propose a simple greedy tag selection algorithm. Second, we give methods for improving the multiplexing rate in large-scale genomic assays by combining primer selection with tag assignment. Experimental results on simulated data show that this integrated optimization leads to reductions of up to 50% in the number of required arrays. 1 Introduction High throughput genomic technologies have revolutionized biomedical sciences, and progress in this area continues at an accelerated pace in response to the increasingly varied needs of biomedical research. Among emerging technologies, one of the most promising is the use of universal tag arrays [4, 7, 8], which provide unprecedented assay customization flexibility while maintaining a high degree of multiplexing and low unit cost. A universal tag array consists of a set of DNA tags, designed such that each tag hybridizes strongly to its own antitag (Watson-Crick complement), but to no other antitag [2]. Genomic assays based on universal arrays involve multiple hybridization steps. A typical assay [3, 5], used for Single Nucleotide Polymor- phism (SNP) genotyping, works as follows. (1) A set of reporter olig