Optimization of primer design for the detection of variable genomic lesions in cancer

Optimization of primer design for the detection of variable genomic lesions in cancer

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Article ID: iaor2009355
Country: United Kingdom
Volume: 23
Start Page Number: 2807
End Page Number: 2815
Publication Date: Jan 2007
Journal: Bioinformatics
Authors: , , , ,
Keywords: medicine
Abstract:

Primer approximation multiplex PCR (PAMP) is a new experimental protocol for efficiently assaying structural variation in genomes. PAMP is particularly suited to cancer genomes where the precise breakpoints of alterations such as deletions or translocations vary between patients. The design of PCR primer sets for PAMP is challenging because a large number of primer pairs are required to detect alterations in the hundreds of kilobases range that can occur in cancer. These sets of primers must achieve high coverage of the region of interest, while avoiding primer dimers and satisfying the physico-chemical constraints of good PCR primers. We describe a natural formulation of these constraints as a combinatorial optimization problem. We show that the PAMP primer design problem is NP-hard, and design algorithms based on simulated annealing and integer programming, that provide good solutions to this problem in practice.

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