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Leonard Bohnenkämper

Publications and source records attributed to Leonard Bohnenkämper.

2 recordsLinked to original sources

Closing the complexity gap of the double distance problem

Genome rearrangement has been an active area of research in computational comparative genomics for the last three decades. While initially mostly an interesting algorithmic endeavor, now the practical application by applying rearrangement distance methods and more advanced phylogenetic tasks is becoming common practice, given the availability of many completely sequenced genomes. Several genome rearrangement models have been developed over time, sometimes with surprising computational properties. A prominent example is the fact that computing the reversal distance of two signed permutations is possible in linear time, while for two unsigned permutations it is NP-hard. Therefore one has always to be careful about the precise problem formulation and complexity analysis of rearrangement problems in order not to be fooled. The double distance is the minimum number of genomic rearrangements between a singular and a duplicated genome that, in addition to rearrangements, are separated by a whole genome duplication. At the same time it allows to assign the genes of the duplicated genome to the two paralogous chromosome copies that existed right after the duplication event. Computing the double distance is another example of a tricky hardness landscape: If the distance measure underlying the double distance is the simple breakpoint distance, the problem can be solved in linear time, while with the more elaborate DCJ distance it is NP-hard. Indeed, there is a family of distance measures, parameterized by an even number k, between the breakpoint distance (k=2) and the DCJ distance (k=\infty). Little was known about the hardness border between these extremes; the problem complexity was known only for k=4 and k=6. In this paper, we close the gap, providing a full picture of the hardness landscape when computing the double distance.

cs.CC↗

Computing the rearrangement distance of natural genomes

The computation of genomic distances has been a very active field of computational comparative genomics over the last 25 years. Substantial results include the polynomial-time computability of the inversion distance by Hannenhalli and Pevzner in 1995 and the introduction of the double-cut and join (DCJ) distance by Yancopoulos et al. in 2005. Both results, however, rely on the assumption that the genomes under comparison contain the same set of unique markers (syntenic genomic regions, sometimes also referred to as genes). In 2015, Shao, Lin and Moret relax this condition by allowing for duplicate markers in the analysis. This generalized version of the genomic distance problem is NP-hard, and they give an ILP solution that is efficient enough to be applied to real-world datasets. A restriction of their approach is that it can be applied only to balanced genomes, that have equal numbers of duplicates of any marker. Therefore it still needs a delicate preprocessing of the input data in which excessive copies of unbalanced markers have to be removed. In this paper we present an algorithm solving the genomic distance problem for natural genomes, in which any marker may occur an arbitrary number of times. Our method is based on a new graph data structure, the multi-relational diagram, that allows an elegant extension of the ILP by Shao, Lin and Moret to count runs of markers that are under- or over-represented in one genome with respect to the other and need to be inserted or deleted, respectively. With this extension, previous restrictions on the genome configurations are lifted, for the first time enabling an uncompromising rearrangement analysis. Any marker sequence can directly be used for the distance calculation. The evaluation of our approach shows that it can be used to analyze genomes with up to a few ten thousand markers, which we demonstrate on simulated and real data.

cs.DS↗