Genome Halving by Block Interchange

We address the problem of finding the minimal number of block interchanges (exchange of two intervals) required to transform a duplicated linear genome into a tandem duplicated linear genome. We provide a formula for the distance as well as a polynomial time algorithm for the sorting problem

Genome Halving by Block Interchange

International audienceWe address the problem of finding the minimal number of block interchanges (exchange of two intervals) required to transform a duplicated linear genome into a tandem duplicated linear genome. We provide a formula for the distance as well as a polynomial time algorithm for the sorting problem

Colored de Bruijn Graphs and the Genome Halving Problem

Breakpoint graph analysis is a key algorithmic technique in studies of genome rearrangements. However, breakpoint graphs are defined only for genomes without duplicated genes, thus limiting their applications in rearrangement analysis. We discuss a connection between the breakpoint graphs and de Bruijn graphs that leads to a generalization of the notion of breakpoint graph for genomes with duplicated genes. We further use the generalized breakpoint graphs to study the Genome Halving Problem (first introduced and solved by Nadia El-Mabrouk and David Sankoff). The El-Mabrouk-Sankoff algorithm is rather complex, and, in this paper, we present an alternative approach that is based on generalized breakpoint graphs. The generalized breakpoint graphs make the El-Mabrouk-Sankoff result more transparent and promise to be useful in future studies of genome rearrangements

Whole Genome Duplications and Contracted Breakpoint Graphs

The genome halving problem, motivated by the whole genome duplication events in molecular evolution, was solved by El-Mabrouk and Sankoff in the pioneering paper [SIAM J. Comput., 32 (2003), pp. 754–792]. The El-Mabrouk–Sankoff algorithm is rather complex, inspiring a quest for a simpler solution. An alternative approach to the genome halving problem based on the notion of the contracted breakpoint graph was recently proposed in [M. A. Alekseyev and P. A. Pevzner, IEEE/ACM Trans. Comput. Biol. Bioinformatics, 4 (2007), pp. 98–107]. This new technique reveals that while the El-Mabrouk–Sankoff result is correct in most cases, it does not hold in the case of unichromosomal genomes. This raises a problem of correcting a flaw in the El- Mabrouk–Sankoff analysis and devising an algorithm that deals adequately with all genomes. In this paper we efficiently classify all genomes into two classes and show that while the El-Mabrouk–Sankoff theorem holds for the first class, it is incorrect for the second class. The crux of our analysis is a new combinatorial invariant defined on duplicated permutations. Using this invariant we were able to come up with a full proof of the genome halving theorem and a polynomial algorithm for the genome halving problem

Genome Halving and Aliquoting Under the Copy Number Distance

Large-scale genome rearrangements occur frequently in species evolution and cancer evolution. While the computation of evolutionary distances is tractable for balanced rearrangements, such as inversions and translocations, computing distances involving duplications and deletions is much more difficult. In the recently proposed Copy Number Distance (CND) model, a genome is represented as a Copy Number Profile (CNP), a sequence of integers, and the CND between two CNPs is the length of a shortest sequence of deletions and amplifications of contiguous segments that transforms one CNP into the other. In addition to these segmental events, genomes also undergo global events such as Whole Genome Duplication (WGD) or polyploidization that multiply the entire genome content. These global events are common and important in both species and cancer evolution. In this paper, we formulate the genome halving problem of finding a closest preduplication CNP that has undergone a WGD and evolved into a given CNP under the CND model. We also formulate the analogous genome aliquoting problem of finding the closest prepolyploidzation CNP under the CND distance. We give a linear time algorithm for the halving distance and a quadratic time dynamic programming algorithm for the aliquoting distance. We implement these algorithms and show that they produce reasonable solutions on simulated CNPs

Guided genome halving: hardness, heuristics and the history of the Hemiascomycetes

Motivation: Some present day species have incurred a whole genome doubling event in their evolutionary history, and this is reflected today in patterns of duplicated segments scattered throughout their chromosomes. These duplications may be used as data to ‘halve’ the genome, i.e. to reconstruct the ancestral genome at the moment of doubling, but the solution is often highly nonunique. To resolve this problem, we take account of outgroups, external reference genomes, to guide and narrow down the search

Genome aliquoting with double cut and join

<p>Abstract</p> <p>Background</p> <p>The <it>genome aliquoting probem </it>is, given an observed genome <it>A </it>with <it>n </it>copies of each gene, presumed to descend from an <it>n</it>-way polyploidization event from an ordinary diploid genome <it>B</it>, followed by a history of chromosomal rearrangements, to reconstruct the identity of the original genome <it>B'</it>. The idea is to construct <it>B'</it>, containing exactly one copy of each gene, so as to minimize the number of rearrangements <it>d</it>(<it>A, B' </it>⊕ <it>B' </it>⊕ ... ⊕ <it>B'</it>) necessary to convert the observed genome <it>B' </it>⊕ <it>B' </it>⊕ ... ⊕ <it>B' </it>into <it>A</it>.</p> <p>Results</p> <p>In this paper we make the first attempt to define and solve the genome aliquoting problem. We present a heuristic algorithm for the problem as well the data from our experiments demonstrating its validity.</p> <p>Conclusion</p> <p>The heuristic performs well, consistently giving a non-trivial result. The question as to the existence or non-existence of an exact solution to this problem remains open.</p

Sobre modelos de rearranjo de genomas

Orientador: João MeidanisTese (doutorado) - Universidade Estadual de Campinas, Instituto de ComputaçãoResumo: Rearranjo de genomas é o nome dado a eventos onde grandes blocos de DNA trocam de posição durante o processo evolutivo. Com a crescente disponibilidade de sequências completas de DNA, a análise desse tipo de eventos pode ser uma importante ferramenta para o entendimento da genômica evolutiva. Vários modelos matemáticos de rearranjo de genomas foram propostos ao longo dos últimos vinte anos. Nesta tese, desenvolvemos dois novos modelos. O primeiro foi proposto como uma definição alternativa ao conceito de distância de breakpoint. Essa distância é uma das mais simples medidas de rearranjo, mas ainda não há um consenso quanto à sua definição para o caso de genomas multi-cromossomais. Pevzner e Tesler deram uma definição em 2003 e Tannier et al. a definiram de forma diferente em 2008. Nesta tese, nós desenvolvemos uma outra alternativa, chamada de single-cut-or-join (SCJ). Nós mostramos que, no modelo SCJ, além da distância, vários problemas clássicos de rearranjo, como a mediana de rearranjo, genome halving e pequena parcimônia são fáceis, e apresentamos algoritmos polinomiais para eles. O segundo modelo que apresentamos é o formalismo algébrico por adjacências, uma extensão do formalismo algébrico proposto por Meidanis e Dias, que permite a modelagem de cromossomos lineares. Esta era a principal limitação do formalismo original, que só tratava de cromossomos circulares. Apresentamos algoritmos polinomiais para o cálculo da distância algébrica e também para encontrar cenários de rearranjo entre dois genomas. Também mostramos como calcular a distância algébrica através do grafo de adjacências, para facilitar a comparação com outras distâncias de rearranjo. Por fim, mostramos como modelar todas as operações clássicas de rearranjo de genomas utilizando o formalismo algébricoAbstract: Genome rearrangements are events where large blocks of DNA exchange places during evolution. With the growing availability of whole genome data, the analysis of these events can be a very important and promising tool for understanding evolutionary genomics. Several mathematical models of genome rearrangement have been proposed in the last 20 years. In this thesis, we propose two new rearrangement models. The first was introduced as an alternative definition of the breakpoint distance. The breakpoint distance is one of the most straightforward genome comparison measures, but when it comes to defining it precisely for multichromosomal genomes, there is more than one way to go about it. Pevzner and Tesler gave a definition in a 2003 paper, and Tannier et al. defined it differently in 2008. In this thesis we provide yet another alternative, calling it single-cut-or-join (SCJ). We show that several genome rearrangement problems, such as genome median, genome halving and small parsimony, become easy for SCJ, and provide polynomial time algorithms for them. The second model we introduce is the Adjacency Algebraic Theory, an extension of the Algebraic Formalism proposed by Meidanis and Dias that allows the modeling of linear chromosomes, the main limitation of the original formalism, which could deal with circular chromosomes only. We believe that the algebraic formalism is an interesting alternative for solving rearrangement problems, with a different perspective that could complement the more commonly used combinatorial graph-theoretic approach. We present polynomial time algorithms to compute the algebraic distance and find rearrangement scenarios between two genomes. We show how to compute the rearrangement distance from the adjacency graph, for an easier comparison with other rearrangement distances. Finally, we show how all classic rearrangement operations can be modeled using the algebraic theoryDoutoradoCiência da ComputaçãoDoutor em Ciência da Computaçã