Primer Selection Methods for Detection of Genomic Inversions and Deletions via PAMP

Primer Approximation Multiplex PCR (PAMP) is a recently introduced experimental technique for detecting large-scale cancer genome lesions such as inversions and deletions from heterogeneous samples containing a mixture of cancer and normal cells. In this paper we give integer linear programming formulations for the problem of selecting sets of PAMP primers that minimize detection failure probability. We also show that PAMP primer selection for detection of anchored deletions cannot be approximated within a factor of 2 − ε, and give a 2-approximation algorithm for a special case of the problem. Experimental results show that our ILP formulations can be used to optimally solve medium size instances of the inversion detection problem, and that heuristics based on iteratively solving ILP formulations for a one-sided version of the problem give near-optimal solutions for anchored deletion detection with highly scalable runtime.