Optimization of probe coverage for high-resolution oligonucleotide aCGH

Motivation: The resolution at which genomic alterations can be mapped by means of oligonucleotide aCGH (array-based comparative genomic hybridization) is limited by two factors: the availability of high-quality probes for the target genomic sequence and the array real-estate. Optimization of the probe selection process is required for arrays that are designed to probe specific genomic regions in very high resolution without compromising probe quality constraints. Results: In this paper we describe a well-defined optimization problem associated with the problem of probe selection for high-resolution aCGH arrays. We propose the whenever possible ∈-cover as a formulation that faithfully captures the requirement of probe selection problem, and provide a fast randomized algorithm that solves the optimization problem in O(n log n) time, as well as a deterministic algorithm with the same asymptotic performance. We apply the method in a typical high-definition array design scenario and demonstrate its superiority with respect to alternative approaches.