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Computing physical maps of chromosomes with nonoverlapping probes by branch-and-cut.pdf

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Computing physical maps of chromosomes with nonoverlapping probes by branch-and-cut

Computing physical maps of chromosomeswith nonoverlapping probes by branch-and-cutThomas Christofy John KececiogluzOctober 9, 1998Abstract We introduce a new combinatorial formulation of chromosome physical-mapping by the sampling-without-replacement protocol. In this protocol, which is simple,inexpensive, and has been used to successfully map several organisms, equal-length clonesare hybridized against a subset of the clones called probes, which are designed to forma maximal nonoverlapping clone-subset. The output of the protocol is the clone-probehybridization matrix H . The problem of nding a maximum-likelihood reconstruction ofthe order of the probes along the chromosome in the presence of false positive and negativehybridization error is equivalent to nding the minimum number of entries of H to changeto zeros so that the resulting matrix has at most 2 ones per row, and the consecutive-ones property across rows. This combinatorial problem, which we call 2-Consecutive-OnesMapping, has a concise integer linear-programming formulation, to which we apply tech-niques from polyhedral combinatorics. The formulation is unique in that it does notexplicitly represent the probe permutation, and in contrast to prior linear-programmingapproaches, the number of variables is small: in practice, linear in the number of clones.We derive a large class of facet-dening inequalities for the 2-consecutive-ones polytopethat we call the augmented k-degree inequalities, and we show that the basic k-degreeclass can be eciently separated using bipartite matchings. Computational results withan implementation of the resulting branch-and-cut algorithm applied to both simulatedand real data from the complete genome of Aspergillus nidulans show that we can solvemany problems to provable optimality and nd maps of higher quality than previouslypossible.Keywords Computational biology, physical mapping of chromosomes, sampling with-out replacement protocol, consecutive ones property, branch