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Daniele Catanzaro , Université Libre de Bruxelles (ULB), Brussels
Martine Labbe , Université Libre de Bruxelles (ULB), Brussels
Bjarni V. Halldorsson , Reykjavik University, Reykjavik
ABSTRACT
A Loss of Heterozygosity (LOH) event occurs when, by the laws of Mendelian inheritance, an individual should be heterozygote at a given site but, due to a deletion polymorphism, is not. Deletions play an important role in human disease and their detection could provide fundamental insights for the development of new diagnostics and treatments. In this article we investigate the Parsimonious Loss of Heterozygosity Problem (PLOHP), i.e., the problem of partitioning suspected polymorphisms from a set of individuals into a minimum number of deletion areas. Specifically, we generalize Halldorsson et al. work by providing a more general formulation of the PLOHP and by showing how one can incorporate different recombination rates and prior knowledge about the locations of deletions. Moreover, we show that the PLOHP can be formulated as a specific version of the clique partition problem in a particular class of graphs called undirected catch-point interval graphs and we prove its general NP-hardness. Finally, we provide a state-of-the-art integer programming formulation and strengthening valid inequalities to exactly solve real instances of the PLOHP containing up to 9000 individuals and 3000 SNPs. Our results give perspectives on the mathematics of the PLOHP and suggest new directions on the development of future efficient exact solution approaches.
INDEX TERMS
Combinatorial algorithms, Computer Applications, Life and Medical Sciences, Biology and genetics, Mathematics of Computing, Numerical Analysis, Optimization, Inter programming, Discrete Mathematics, Combinatorics
CITATION
Daniele Catanzaro, Martine Labbe, Bjarni V. Halldorsson, "An Integer Programming Formulation of the Parsimonious Loss of Heterozygosity Problem", IEEE/ACM Transactions on Computational Biology and Bioinformatics, , no. 1, pp. 1, PrePrints PrePrints, doi:10.1109/TCBB.2012.138
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