Aïda Ouangraoua

Yeast ancestral genome reconstructions: the possibilities of computational methods II.

Since the availability of assembled eukaryotic genomes, the first one being a budding yeast, many computational methods for the reconstruction of ancestral karyotypes and gene orders have been developed. The difficulty has always been to assess their reliability, since we often miss a good knowledge of the true ancestral genomes to compare their results to, as well as a good knowledge of the evolutionary mechanisms to test them on realistic simulated data. In this study, we propose some measures of reliability of several kinds of methods, and apply them to infer and analyse the architectures of two ancestral yeast genomes, based on the sequence of seven assembled extant ones. The pre-duplication common ancestor of S. cerevisiae and C. glabrata has been inferred manually by Gordon et al. (Plos Genet. 2009). We show why, in this case, a good convergence of the methods is explained by some properties of the data, and why results are reliable. In another study, Jean et al. (J. Comput Biol. 2009) proposed an ancestral architecture of the last common ancestor of S. kluyveri, K. thermotolerans, K. lactis, A. gossypii, and Z. rouxii inferred by a computational method. In this case, we show that the dataset does not seem to contain enough information to infer a reliable architecture, and we construct a higher resolution dataset which gives a good reliability on a new ancestral configuration.

Reconstructing the architecture of the ancestral amniote genome

MOTIVATION The ancestor of birds and mammals lived approximately 300 million years ago. Inferring its genome organization is key to understanding the differentiated evolution of these two lineages. However, detecting traces of its chromosomal organization in its extant descendants is difficult due to the accumulation of molecular evolution since birds and mammals lineages diverged. RESULTS We address several methodological issues for the detection and assembly of ancestral genomic features of ancient vertebrate genomes, which encompass adjacencies, contiguous segments, syntenies and double syntenies in the context of a whole genome duplication. Using generic, but stringent, methods for all these problems, some of them new, we analyze 15 vertebrate genomes, including 12 amniotes and 3 teleost fishes, and infer a high-resolution genome organization of the amniote ancestral genome, composed of 39 ancestral linkage groups at a resolution of 100 kb. We extensively discuss the validity and robustness of the method to variations of data and parameters. We introduce a support value for each of the groups, and show that 36 out of 39 have maximum support. CONCLUSIONS Single methodological principle cannot currently be used to infer the organization of the amniote ancestral genome, and we demonstrate that it is possible to gather several principles into a computational paleogenomics pipeline. This strategy offers a solid methodological base for the reconstruction of ancient vertebrate genomes. AVAILABILITY Source code, in C++ and Python, is available at http://www.cecm.sfu.ca/~cchauve/SUPP/AMNIOTE2010/ CONTACT cedric.chauve@sfu.ca SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.

BRASERO: A Resource for Benchmarking RNA Secondary Structure Comparison Algorithms

The pairwise comparison of RNA secondary structures is a fundamental problem, with direct application in mining databases for annotating putative noncoding RNA candidates in newly sequenced genomes. An increasing number of software tools are available for comparing RNA secondary structures, based on different models (such as ordered trees or forests, arc annotated sequences, and multilevel trees) and computational principles (edit distance, alignment). We describe here the website BRASERO that offers tools for evaluating such software tools on real and synthetic datasets.

Local similarity between quotiented ordered trees

In this paper we propose a dynamic programming algorithm to evaluate local similarity between ordered quotiented trees using a constrained edit scoring scheme. A quotiented tree is a tree defined with an additional equivalent relation on vertices and such that the quotient graph is also a tree. The core of the method relies on two adaptations of an algorithm proposed by Zhang et al. [K. Zhang, D. Shasha, Simple fast algorithms for the editing distance between trees and related problems (1989) 1245-1262] for comparing ordered rooted trees. After some preliminary definitions and the description of this tree edit algorithm, we propose extensions to globally and locally compare two quotiented trees. This last method allows to find the region in each tree with the highest similarity. Algorithms are currently being used in genomic analysis to evaluate variability between RNA secondary structures.

Comparison of tree architecture using tree edit distances: application to 2-year-old apple hybrids

In fruit trees, understanding genetic determinisms of architectural traits is considered as a promising manner to control vegetative development and yield regularity. In this context, our study aimed to classify 2-year-old apple hybrids on the basis of their architectural traits. From a fine phenotyping, trees were described as tree graphs, including topological and geometric information. To evaluate the similarity between trees, comparison methods based on edit operations (substitution, insertion and deletion) were carried out. Distance between two tree graphs was computed by minimising the sum of the costs of the edit operations applied to transform one tree into another. Two algorithms for the comparison of unordered and partially ordered tree graphs were applied to a sub-sample of the population, taking into account several geometric attributes. For each comparison, a dissimilarity matrix was computed, and subsequently trees were clustered. A local interpretation of the matched entities was proposed through schematic representations of the trees, and similarities between trees were analysed within and between clusters. The tree graphs, both unordered or partially ordered and whether the attributes were considered or not, were grouped, by clustering, according to the number of entities per tree. The robustness of the unordered comparison was demonstrated by its application to the whole population, since it provided results similar to those obtained on the sub-sample. Further developments towards a higher relative weight of geometric versus topological information are discussed in the perspective to define an architectural ideotype in apple.

Genome dedoubling by DCJ and reversal

BackgroundSegmental duplications in genomes have been studied for many years. Recently, several studies have highlighted a biological phenomenon called breakpoint-duplication that apparently associates a significant proportion of segmental duplications in Mammals, and the Drosophila species group, to breakpoints in rearrangement events.ResultsIn this paper, we introduce and study a combinatorial problem, inspired from the breakpoint-duplication phenomenon, called the Genome Dedoubling Problem. It consists of finding a minimum length rearrangement scenario required to transform a genome with duplicated segments into a non-duplicated genome such that duplications are caused by rearrangement breakpoints. We show that the problem, in the Double-Cut-and-Join (DCJ) and the reversal rearrangement models, can be reduced to an APX-complete problem, and we provide algorithms for the Genome Dedoubling Problem with 2-approximable parts. We apply the methods for the reconstruction of a non-duplicated ancestor of Drosophila yakuba.ConclusionsWe present the Genome Dedoubling Problem, and describe two algorithms solving the problem in the DCJ model, and the reversal model. The usefulness of the problems and the methods are showed through an application to real Drosophila data.

ProCARs: Progressive Reconstruction of Ancestral Gene Orders

BackgroundIn 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).ResultsIn 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.ConclusionWe 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, written in Python, and the dataset used in this paper are available at http://bioinfo.lifl.fr/procars/.

Parking Functions, Labeled Trees and DCJ Sorting Scenarios

In genome rearrangement theory, one of the elusive questions raised in recent years is the enumeration of rearrangement scenarios between two genomes. This problem is related to the uniform generation of rearrangement scenarios, and the derivation of tests of statistical significance of the properties of these scenarios. Here we give an exact formula for the number of double-cut-and-join (DCJ) rearrangement scenarios of co-tailed genomes. We also construct effective bijections between the set of scenarios that sort a cycle and well studied combinatorial objects such as parking functions and labeled trees.

The SCJ Small Parsimony Problem for Weighted Gene Adjacencies

Reconstructing ancestral gene orders in a given phylogeny is a classical problem in comparative genomics. Most existing methods compare conserved features in extant genomes in the phylogeny to define potential ancestral gene adjacencies, and either try to reconstruct all ancestral genomes under a global evolutionary parsimony criterion, or, focusing on a single ancestral genome, use a scaffolding approach to select a subset of ancestral gene adjacencies, generally aiming at reducing the fragmentation of the reconstructed ancestral genome. In this paper, we describe an exact algorithm for the Small Parsimony Problem that combines both approaches. We consider that gene adjacencies at internal nodes of the species phylogeny are weighted, and we introduce an objective function defined as a convex combination of these weights and the evolutionary cost under the Single-Cut-or-Join (SCJ) model. The weights of ancestral gene adjacencies can, e.g., be obtained through the recent availability of ancient DNA sequencing data, which provide a direct hint at the genome structure of the considered ancestor, or through probabilistic analysis of gene adjacencies evolution. We show the NP-hardness of our problem variant and propose a Fixed-Parameter Tractable algorithm based on the Sankoff-Rousseau dynamic programming algorithm that also allows to sample co-optimal solutions. We apply our approach to mammalian and bacterial data providing different degrees of complexity. We show that including adjacency weights in the objective has a significant impact in reducing the fragmentation of the reconstructed ancestral gene orders. An implementation is available at http://github.com/nluhmann/PhySca.

A constrained edit distance algorithm between semi-ordered trees

In this paper, we propose a formal definition of a new class of trees called semi-ordered trees and a polynomial dynamic programming algorithm to compute a constrained edit distance between such trees. The core of the method relies on a similar approach to compare unordered [Kaizhong Zhang, A constrained edit distance between unordered labeled trees, Algorithmica 15 (1996) 205-222] and ordered trees [Kaizhong Zhang, Algorithms for the constrained editing distance between ordered labeled trees and related problems, Pattern Recognition 28 (3) (1995) 463-474]. The method is currently applied to evaluate the similarity between architectures of apple trees [Vincent Segura, Aida Ouangraoua, Pascal Ferraro, Evelyne Costes, Comparison of tree architecture using tree edit distances: Application to two-year-old apple tree, Euphytica 161 (2007) 155-164].