Minimal Conflicting Sets for the Consecutive Ones Property in ancestral genome reconstruction

A binary matrix has the Consecutive Ones Property (C1P) if its columns can be ordered in such a way that all 1's on each row are consecutive. A Minimal Conflicting Set is a set of rows that does not have the C1P, but every proper subset has the C1P. Such submatrices have been considered in comparative genomics applications, but very little is known about their combinatorial structure and efficient algorithms to compute them. We first describe an algorithm that detects rows that belong to Minimal Conflicting Sets. This algorithm has a polynomial time complexity when the number of 1's in each row of the considered matrix is bounded by a constant. Next, we show that the problem of computing all Minimal Conflicting Sets can be reduced to the joint generation of all minimal true clauses and maximal false clauses for some monotone boolean function. We use these methods on simulated data related to ancestral genome reconstruction to show that computing Minimal Conflicting Set is useful in discriminating between true positive and false positive ancestral syntenies. We also study a dataset of yeast genomes and address the reliability of an ancestral genome proposal of the Saccahromycetaceae yeasts.Comment: 20 pages, 3 figure

A Methodological Framework for the Reconstruction of Contiguous Regions of Ancestral Genomes and Its Application to Mammalian Genomes

The reconstruction of ancestral genome architectures and gene orders from homologies between extant species is a long-standing problem, considered by both cytogeneticists and bioinformaticians. A comparison of the two approaches was recently investigated and discussed in a series of papers, sometimes with diverging points of view regarding the performance of these two approaches. We describe a general methodological framework for reconstructing ancestral genome segments from conserved syntenies in extant genomes. We show that this problem, from a computational point of view, is naturally related to physical mapping of chromosomes and benefits from using combinatorial tools developed in this scope. We develop this framework into a new reconstruction method considering conserved gene clusters with similar gene content, mimicking principles used in most cytogenetic studies, although on a different kind of data. We implement and apply it to datasets of mammalian genomes. We perform intensive theoretical and experimental comparisons with other bioinformatics methods for ancestral genome segments reconstruction. We show that the method that we propose is stable and reliable: it gives convergent results using several kinds of data at different levels of resolution, and all predicted ancestral regions are well supported. The results come eventually very close to cytogenetics studies. It suggests that the comparison of methods for ancestral genome reconstruction should include the algorithmic aspects of the methods as well as the disciplinary differences in data aquisition

ProCARs: Progressive Reconstruction of Ancestral Gene Orders

International audienceBackground: In the context of ancestral gene order reconstruction from extant genomes, there exist two main computational approaches: rearrangement-based, and homology-based methods. The rearrangement-based methods consist in minimizing a total rearrangement distance on the branches of a species tree. The homology-based methods consist in the detection of a set of potential ancestral contiguity features, followed by the assembling of these features into Contiguous Ancestral Regions (CARs). Results: In this paper, we present a new homology-based method that uses a progressive approach for both the detection and the assembling of ancestral contiguity features into CARs. The method is based on detecting a set of potential ancestral adjacencies iteratively using the current set of CARs at each step, and constructing CARs progressively using a 2-phase assembling method. We show the usefulness of the method through a reconstruction of the boreoeutherian ancestral gene order, and a comparison with three other homology-based methods: AnGeS, InferCARs and GapAdj. The program is written in Python, and the dataset used in this paper are available at http://bioinfo.lifl.fr/procars/

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

Consistency-based detection of potential tumor-specific deletions in matched normal/tumor genomes

Wittler R, Chauve C. Consistency-based detection of potential tumor-specific deletions in matched normal/tumor genomes. BMC Bioinformatics. 2011;12(Suppl. 9):S21

Linear-Time Algorithms for Finding Tucker Submatrices and Lekkerkerker-Boland Subgraphs

Lekkerkerker and Boland characterized the minimal forbidden induced subgraphs for the class of interval graphs. We give a linear-time algorithm to find one in any graph that is not an interval graph. Tucker characterized the minimal forbidden submatrices of binary matrices that do not have the consecutive-ones property. We give a linear-time algorithm to find one in any binary matrix that does not have the consecutive-ones property.Comment: A preliminary version of this work appeared in WG13: 39th International Workshop on Graph-Theoretic Concepts in Computer Scienc

Exploiting natural selection to study adaptive behavior

The research presented in this dissertation explores different computational and modeling techniques that combined with predictions from evolution by natural selection leads to the analysis of the adaptive behavior of populations under selective pressure. For this thesis three computational methods were developed: EXPLoRA, EVORhA and SSA-ME. EXPLoRA finds genomic regions associated with a trait of interests (QTL) by explicitly modeling the expected linkage disequilibrium of a population of sergeants under selection. Data from BSA experiments was analyzed to find genomic loci associated with ethanol tolerance. EVORhA explores the interplay between driving and hitchhiking mutations during evolution to reconstruct the subpopulation structure of clonal bacterial populations based on deep sequencing data. Data from mixed infections and evolution experiments of E. Coli was used and their population structure reconstructed. SSA-ME uses mutual exclusivity in cancer to prioritize cancer driver genes. TCGA data of breast cancer tumor samples were analyzed.status: publishe