Exact and Approximation Algorithms for Computing Reversal Distances in Genome Rearrangement

Genome rearrangement is a research area capturing wide attention in molecular biology. The reversal distance problem is one of the most widely studied models of genome rearrangements in inferring the evolutionary relationship between two genomes at chromosome level. The problem of estimating reversal distance between two genomes is modeled as sorting by reversals. While the problem of sorting signed permutations can have polynomial time solutions, the problem of sorting unsigned permutations has been proven to be NP-hard [4]. This work introduces an exact greedy algorithm for sorting by reversals focusing on unsigned permutations. An improved method of producing cycle decompositions for a 3/2-approximation algorithm and the consideration of 3-cycles for reversal sequences are also presented in this paper

Polynomial-time sortable stacks of burnt pancakes

Pancake flipping, a famous open problem in computer science, can be formalised as the problem of sorting a permutation of positive integers using as few prefix reversals as possible. In that context, a prefix reversal of length k reverses the order of the first k elements of the permutation. The burnt variant of pancake flipping involves permutations of signed integers, and reversals in that case not only reverse the order of elements but also invert their signs. Although three decades have now passed since the first works on these problems, neither their computational complexity nor the maximal number of prefix reversals needed to sort a permutation is yet known. In this work, we prove a new lower bound for sorting burnt pancakes, and show that an important class of permutations, known as "simple permutations", can be optimally sorted in polynomial time.Comment: Accepted pending minor revisio

Approximating the double-cut-and-join distance between unsigned genomes

In this paper we study the problem of sorting unsigned genomes by double-cut-and-join operations, where genomes allow a mix of linear and circular chromosomes to be present. First, we formulate an equivalent optimization problem, called maximum cycle/path decomposition, which is aimed at finding a largest collection of edge-disjoint cycles/AA-paths/AB-paths in a breakpoint graph. Then, we show that the problem of finding a largest collection of edge-disjoint cycles/AA-paths/AB-paths of length no more than l can be reduced to the well-known degree-bounded k-set packing problem with k = 2l. Finally, a polynomial-time approximation algorithm for the problem of sorting unsigned genomes by double-cut-and-join operations is devised, which achieves the approximation ratio for any positive ε. For the restricted variation where each genome contains only one linear chromosome, the approximation ratio can be further improved t

Sorting by Prefix Block-Interchanges

We initiate the study of sorting permutations using prefix block-interchanges, which exchange any prefix of a permutation with another non-intersecting interval. The goal is to transform a given permutation into the identity permutation using as few such operations as possible. We give a 2-approximation algorithm for this problem, show how to obtain improved lower and upper bounds on the corresponding distance, and determine the largest possible value for that distance

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

Kernelization of Whitney Switches

A fundamental theorem of Whitney from 1933 asserts that 2-connected graphs G and H are 2-isomorphic, or equivalently, their cycle matroids are isomorphic, if and only if G can be transformed into H by a series of operations called Whitney switches. In this paper we consider the quantitative question arising from Whitney's theorem: Given two 2-isomorphic graphs, can we transform one into another by applying at most k Whitney switches? This problem is already NP-complete for cycles, and we investigate its parameterized complexity. We show that the problem admits a kernel of size O(k), and thus, is fixed-parameter tractable when parameterized by k.Comment: To appear at ESA 202

Kernelization of Whitney Switches

A fundamental theorem of Whitney from 1933 asserts that 2-connected graphs $G$ and $H$ are 2-isomorphic, or equivalently, their cycle matroids are isomorphic if and only if $G$ can be transformed into $H$ by a series of operations called Whitney switches. In this paper we consider the quantitative question arising from Whitney's theorem: Given two 2-isomorphic graphs, can we transform one into another by applying at most $k$ Whitney switches? This problem is already \sf NP-complete for cycles, and we investigate its parameterized complexity. We show that the problem admits a kernel of size $\mathcal{O}(k)$ and thus is fixed-parameter tractable when parameterized by $k$.publishedVersio

Genome Rearrangement Problems

Various global rearrangements of permutations, such as reversals and transpositions, have recently become of interest because of their applications in computational molecular biology. A reversal is an operation that reverses the order of a substring of a permutation. A transposition is an operation that swaps two adjacent substrings of a permutation. The problem of determining the smallest number of reversals required to transform a given permutation into the identity permutation is called sorting by reversals. Similar problems can be defined for transpositions and other global rearrangements. Related to sorting by reversals is the problem of establishing the reversal diameter. The reversal diameter of Sn (the symmetric group on n elements) is the maximum number of reversals required to sort a permutation of length n. Of course, diameter problems can be posed for other global rearrangements. These various problems are of interest because the permutations can be used to represent sequences of genes in chromosomes, and the global rearrangements then represent evolutionary events. As a result, we call these problems genome rearrangement problems. Genome rearrangement problems seem to be unlike previously studied algorithmic problems on sequences, so new methods have had to be developed to deal with them. These methods predominantly employ graphs to model permutation structure. However, even using these methods, often a genome rearrangement problem has no obvious polynomial-time algorithm, and in some cases can be shown to be NP-hard. For example, the problem of sorting by reversals is NP-hard, whereas the computational complexity of sorting by transpositions is open. For problems like these, it is natural to seek polynomial-time approximation algorithms that achieve an approximation guarantee. In this thesis, we study several genome rearrangement problems as interesting and challenging algorithmic problems in their own right, including some problems for which the global rearrangement has no immediate biological equivalent. For example, we define a block-interchange to be a rearrangement that swaps any two substrings of the permutation. We examine, in particular, how the graph theoretic models relate to the genome rearrangement problems that we study. The major new results contained in this thesis are as follows: We present a 3/2-approximation algorithm for sorting by reversals. This is the best known approximation algorithm for the problem, and improves upon the 7/4 approximation bound of the previous best algorithm. We give a polynomial-time algorithm for a significant special case of sorting by reversals, thereby disproving a conjecture of Kececioglu and Sankoff, who had suggested that this special case was likely to be NP-hard. We analyse the structure of the so-called cpcle graph of a permutation in the context of sorting by transpositions, and thereby gain a deeper insight into this problem. Among the consequences are; a tighter lower bound for the problem, a simpler 3/2-aproximation algorithm than had previously been described, and algorithms that, in empirical tests, almost always find the exact transposition distance of random permutations. We introduce a natural generalisation of sorting by transpositions called sorting by block-interchanges, and present a polynomial-time algorithm for this problem. We initiate the study of analogous problems on strings over a fixed length alphabet. We establish upper and lower bounds and diameter results for the problems over a binary alphabet. We also prove that the problems analogous to sorting by reversals and sorting by block-interchanges are NP-hard. (Abstract shortened by ProQuest.)

A fast algorithm for the multiple genome rearrangement problem with weighted reversals and transpositions

<p>Abstract</p> <p>Background</p> <p>Due to recent progress in genome sequencing, more and more data for phylogenetic reconstruction based on rearrangement distances between genomes become available. However, this phylogenetic reconstruction is a very challenging task. For the most simple distance measures (the breakpoint distance and the reversal distance), the problem is NP-hard even if one considers only three genomes.</p> <p>Results</p> <p>In this paper, we present a new heuristic algorithm that directly constructs a phylogenetic tree w.r.t. the weighted reversal and transposition distance. Experimental results on previously published datasets show that constructing phylogenetic trees in this way results in better trees than constructing the trees w.r.t. the reversal distance, and recalculating the weight of the trees with the weighted reversal and transposition distance. An implementation of the algorithm can be obtained from the authors.</p> <p>Conclusion</p> <p>The possibility of creating phylogenetic trees directly w.r.t. the weighted reversal and transposition distance results in biologically more realistic scenarios. Our algorithm can solve today's most challenging biological datasets in a reasonable amount of time.</p