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Register a new userComputing the rearrangement distance of natural genomes
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Added by
Jens Stoye
Publication date
2020
fields
Informatics Engineering
and research's language is
English
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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.
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The inversion distance, that is the distance between two unichromosomal genomes with the same content allowing only
A classical problem in comparative genomics is to compute the rearrangement distance, that is the minimum number of large-scale rearrangements required to transform a given genome into another given genome. While the most traditional approaches in this area are family-based, i.e., require the classification of DNA fragments into families, more recently an alternative family-free approach was proposed, and consists of studying the rearrangement distances without prior family assignment. On the one hand the computation of genomic distances in the family-free setting helps to match occurrences of duplicated genes and find homologies, but on the other hand this computation is NP-hard. In this paper, by letting structural rearrangements be represented by the generic double cut and join (DCJ) operation and also allowing insertions and deletions of DNA segments, we propose a new and more general family-free genomic distance, providing an efficient ILP formulation to solve it. Our experiments show that the ILP produces accurate results and can handle not only bacterial genomes, but also fungi and insects, or subsets of chromosomes of mammals and plants.
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