Statistique des comparaisons de génomes complets bactériens

La génomique comparative est l'étude des relations structurales et fonctionnelles entre des génomes appartenant à différentes souches ou espèces. Cette discipline offre ainsi la possibilité d'étudier et de comprendre les processus qui façonnent les génomes au cours de l'évolution. Dans le cadre de cette thèse, nous nous sommes intéressés à la génomique comparative des bactéries et plus particulièrement aux méthodes relatives à la comparaison des séquences complètes d'ADN des génomes bactériens. Ces dix dernières années, le développement d'outils informatiques permettant de comparer des génomes entiers à l'échelle de l'ADN est devenu une thématique de recherche à part entière. Actuellement, il existe de nombreux outils dédiés à cette tâche. Cependant, jusqu'à présent, la plupart des efforts ont été dirigés vers la réduction du temps de calcul et l'optimisation de la mémoire au détriment de l'évaluation de la qualité des résultats obtenus. Pour combler ce vide, nous avons travaillé sur différents problèmes statistiques soulevés par la comparaison de génomes complets bactériens. Notre travail se divise en deux axes de recherche. Dans un premier temps, nous nous sommes employés à évaluer la robustesse des alignements de génomes complets bactériens. Nous avons proposé une méthode originale fondée sur l'application de perturbations aléatoires sur les génomes comparés. Trois scores différents sont alors calculés pour estimer la robustesse des alignements de génomes à différentes échelles, allant des nucléotides aux séquences entières des génomes. Notre méthode a été expérimentée sur des données génomiques bactériennes réelles. Nos scores permettent d'identifier à la fois les alignements robustes et non robustes. Ils peuvent être employés pour corriger un alignement ou encore pour comparer plusieurs alignements obtenus à partir de différents outils. Dans un second temps, nous avons étudié le problème de la paramétrisation des outils de comparaisons de génomes entiers. En effet, la plupart des outils existants manquent à la fois de documentation et de valeurs par défaut fiables pour initialiser leurs paramètres. Conséquemment, il y a un besoin crucial de méthodes spécifiques pour aider les utilisateurs à définir des valeurs appropriées pour les paramètres de ces outils. Une grande partie des outils de comparaisons de génomes complets est fondée sur la détection des matches (mots communs exacts). Le paramètre essentiel pour ces méthodes est la longueur des matches à considérer. Au cours de cette thèse, nous avons développé deux méthodes statistiques pour estimer une valeur optimale pour la taille des matches. Notre première approche utilise un modèle de mélange de lois géométriques pour caractériser la distribution de la taille des matches obtenus lorsque l'on compare deux séquences génomiques. La deuxième approche est fondée sur une approximation de Poisson de la loi du comptage des matches entre deux chaînes de Markov. Ces méthodes statistiques nous permettent d'identifier facilement une taille optimale de matches à la fois pour des séquences simulées et pour des données génomiques réelles. Nous avons également montré que cette taille optimale dépend des caractéristiques des génomes comparés telles que leur taille, leur composition en base ou leur divergence relative. Cette thèse représente une des toutes premières études dont l'objectif est d'évaluer et d'améliorer la qualité des comparaisons des génomes complets. L'intérêt et les limites de nos différentes approches sont discutés et plusieurs perspectives d'évolution sont proposées.Comparative genomics is the study of the structural and functional relationships between genomes belonging to different strains or species. This discipline offers great opportunities to investigate and to understand the processes that shape genomes across the evolution. In this thesis, we focused on the comparative genomics of bacteria and more precisely, on methods dedicated to the comparison of the complete DNA sequences of bacterial genomes. This last decade, the design of specific computerized methods to compare complete genomes at the DNA scale has become a subject of first concern. Now, there exist many tools and methods dedicated to this task. However, until now, most of the efforts were directed to reduce execution time and memory usage at the expense of the evaluation of the quality of the results. To fill this gap, we worked on different statistical issues related to the comparison of complete bacterial genomes. Our work was conducted into two directions. In the first one, we investigated the assessment of the robustness of complete bacterial genome alignments. We proposed an original method based on random perturbations of the compared genomes. Three different scores were derived to estimate the robustness of genome alignments at different scales, from nucleotides to the complete genome sequences. Our method was trained on bacterial genomic data. Our scores allow us to identify robust and non robust genome alignments. They can be used to correct an alignment or to compare alignments performed with different tools. Secondly, we studied the problem of the parametrization of comparison tools. Briefly, most of the existing tools suffer from a lack of information and of reliable default values to set their parameters. Consequently, there is a crucial need of methods to help users to define reliable parameter values for these tools. Most of the comparison tools are rooted on the detection of word matches. The key parameter for all these tools is the length of the matches to be considered. During this thesis, we developed two statistical methods to estimate an optimal length for these matches. Our first approach consisted in using a mixture model of geometric distributions to characterize the distribution of the length of matches retrieved from the comparison of two genomic sequences. The second approach is rooted on a Poisson approximation of the number of matches between two Markov chains. These statistical methods allow us to easily identify an optimal length for the matches from both simulated and real genomic data. We also showed that this optimal length depends on the characteristics of the compared genomes such as their length, their nucleotide composition, and their relative divergence. This thesis represents one of the earliest attempts to statistically evaluate and to improve the quality of complete genome comparisons. The interest and limitations of our different methods are discussed and some perspectives are proposed.EVRY-Bib. électronique (912289901) / SudocSudocFranceF

Sovereign Credit Risk Analysis for Selected Asian and European Countries

We analyze the nature of sovereign credit risk for selected Asian and European countries through a set of sovereign CDS data for an eighty-year period that includes the episode of the 2008-2009 financial crisis. Our principal component analysis results suggest that there is strong commonality in sovereign credit risk across countries after the crisis. The regression tests show that the commonality is linked to both local and global financial and economic variables. Besides, we also notice intriguing differences in the sovereign credit risk behavior of Asian and European countries. Specifically, we find that some variables, including foreign reserve, global stock market, and volatility risk premium, affect the of Asian and European sovereign credit risks in the opposite direction. Further, we assume that the arrival rates of credit events follow a square-root diffusion from which we build our pricing model. The resulting model is used to decompose credit spreads into risk premium and credit-event components

Reconstruction of ancestral chromosome architecture and gene repertoire reveals principles of genome evolution in a model yeast genus

International audienceReconstructing genome history is complex but necessary to reveal quantitative principles governing genome evolution. Such reconstruction requires recapitulating into a single evolutionary framework the evolution of genome architecture and gene repertoire. Here, we reconstructed the genome history of the genus Lachancea that appeared to cover a continuous evolutionary range from closely related to more diverged yeast species. Our approach integrated the generation of a high-quality genome data set; the development of AnChro, a new algorithm for reconstructing ancestral genome architecture; and a comprehensive analysis of gene repertoire evolution. We found that the ancestral genome of the genus Lachancea contained eight chromosomes and about 5173 protein-coding genes. Moreover, we characterized 24 horizontal gene transfers and 159 putative gene creation events that punctuated species diversification. We retraced all chromosomal rearrangements, including gene losses, gene duplications, chromosomal inversions and translocations at single gene resolution. Gene duplications outnumbered losses and balanced rearrangements with 1503, 929, and 423 events, respectively. Gene content variations between extant species are mainly driven by differential gene losses, while gene duplications remained globally constant in all lineages. Remarkably, we discovered that balanced chromosomal rearrangements could be responsible for up to 14% of all gene losses by disrupting genes at their breakpoints. Finally, we found that nonsynonymous substitutions reached fixation at a coordinated pace with chromosomal inversions, translocations, and duplications, but not deletions. Overall, we provide a granular view of genome evolution within an entire eukaryotic genus, linking gene content, chromosome rearrangements , and protein divergence into a single evolutionary framework

Artisanal and farmer bread making practices differently shape fungal species community composition in French sourdoughs

Preserving microbial diversity in food systems is one of the many challenges to be met to achieve food security and quality. Although industrialization led to the selection and spread of specific fermenting microbial strains, there are still ongoing artisanal processes that may allow the conservation of a wider species diversity and genetic diversity. We examined whether the diversity of artisanal practices could lead to an increased level in fungal species diversity for bread making. We used an interdisciplinary participatory research approach including bakers, psycho-sociologists and microbiologists to analyze French bread making practices and describe fungal communities in naturally fermented sourdough of 27 bakers and 12 farmer bakers. Bread making practices were classified in two groups: the farmer-like practice group and the artisanal-like practice group. The well-known bakery yeast, Saccharomyces cerevisiae, was dominant (i.e. with a relative abundance over 50%) in only 24% of sourdoughs while other yeast species, belonging to the Kazachstania genus, were dominant in 54% of sourdoughs. Bread making practices were found to drive the distribution of fungal species across sourdoughs. The most striking bread making practice effect was the occurrence of Kazachstania humilis in sourdoughs made with artisanal-like practices and the occurrence of Kazachstania bulderi in sourdoughs made with farmer-like practices. Phenotypic divergences between sourdough and non-sourdough strains were found for K. humilis but not for K. bulderi. Overall, our results showed that preserving bread making practice diversity allows the preservation of a higher species and phenotypic diversity in microbial communities

Lethal and Sublethal Effects of Pyriproxyfen on Apis and Non-Apis Bees

Pyriproxyfen is a juvenile hormone mimic used extensively worldwide to fight pests in agriculture and horticulture. It also has numerous applications as larvicide in vector control. The molecule disrupts metamorphosis and adult emergence in the target insects. The same types of adverse effects are expected on non-target insects. In this context, the objective of this study was to evaluate the existing information on the toxicity of pyriproxyfen on the honey bee (Apis mellifera) and non-Apis bees (bumble bees, solitary bees, and stingless bees). The goal was also to identify the gaps necessary to fill. Thus, whereas the acute and sublethal toxicity of pyriproxyfen against A. mellifera is well-documented, the information is almost lacking for the non-Apis bees. The direct and indirect routes of exposure of the non-Apis bees to pyriproxyfen also need to be identified and quantified. More generally, the impacts of pyriproxyfen on the reproductive success of the different bee species have to be evaluated as well as the potential adverse effects of its metabolites

The use by a public entity of property of others. Research on the status of a public tenant

Les personnes publiques ne sont pas propriétaires de tous les biens qu’elles utilisent. Elles louent ou empruntent souvent les biens nécessaires à l’exercice de leurs missions. L’utilisation du bien d’autrui n’est plus envisagée comme la solution par défaut qu’elle fut longtemps. A cette fin, les personnes publiques optent pour des procédés juridiques multiples. Titulaires de la capacité à contracter, elles concluent des baux civils ou commerciaux, des prêts à usage ou des usufruits conventionnels. Elles peuvent également recourir à des procédés de droit public, tels que les marchés publics de fournitures ou les marchés de partenariat. Enfin, certains mécanismes non-conventionnels permettent également cette déconnexion entre l’usage et la propriété. En vertu d’une prérogative de puissance publique particulièrement exorbitante, l’administration est habilitée à capter unilatéralement un droit d’usage dans le patrimoine d’autrui, via son pouvoir de réquisition, par exemple. L’aptitude unique de l’administration à jouer ainsi sur plusieurs tableaux est la marque de son irréductible spécificité.L’utilisation du bien d’autrui par une personne publique est en principe le support d’une mission ou d’une tâche d’intérêt général. Pour cette raison, son exécution doit respecter les nécessités de l’action publique, ensemble de principes et exigences juridiques qui impliquent que les activités administratives soient mises en œuvre de manière efficace et sans interruption, à l’aide de moyens adaptés et dans de bonnes conditions financières. A cet égard, l’utilisation du bien d’autrui présente des atouts dont l’exercice du droit de propriété est dépourvu, au moins dans deux circonstances. Les besoins de courte durée, qu’ils soient ponctuels ou discontinus, sont mieux assouvis par la location, le prêt à usage, ou la réquisition, que par l’acquisition d’un bien. La même remarque s’applique, avec quelques nuances, à la satisfaction des besoins complexes de l’administration. Mais la difficile adaptation à l’évolution des besoins et la précarité qui caractérise un nombre important de ces techniques juridiques présente le risque d’une certaine perte de maîtrise, qui peut mettre à mal la continuité, la mutabilité, la « qualité » et la « performance » du service public auquel le bien loué est affecté. Dès lors, le droit public est appelé à réagir. Un régime juridique unifié pourrait être appliqué à l’ensemble des biens utilisés par l’administration, quel qu’en soit le propriétaire, dans le cadre de la mise en œuvre d’une activité de service public. Ces règles s’attacheraient à rendre l’utilisation inviolable, abstraction faite de l’instrument juridique qui fonde l’exercice du droit d’usage ou de jouissance par la personne publique.Public entities do not own all the goods they use. They often rent or borrow the assets necessary for the performance of their missions. The use of the property of others is no longer considered as the default solution that it was for a long time. To this end, public entities opt for multiple legal processes. Holders of the capacity to contract, they conclude civil or commercial leases, loans or conventional usufruct. They may also use public law procedures, such as public supply contracts or partnership contracts. Finally, some non-conventional mechanisms also allow this disconnection between use and ownership. By virtue of a particularly exorbitant prerogative of public power, the administration is empowered to unilaterally capture a right of use in the patrimony of others, for example, by its power of requisition. The unique ability of the administration to play thus on several tables is the mark of its irreducible specificity.The use of the property of others by a public person is in principle the support of a mission or task of general interest. For this reason, its execution must respect the requirements of public action, a set of principles and legal requirements which imply that administrative activities must be carried out efficiently and without interruption, using appropriate and appropriate means financial conditions. In this respect, the use of the property of others presents assets whose exercise of the right of ownership is devoid, at least in two circumstances. Short-term needs, whether they are punctual or discontinuous, are better satisfied by renting, using loans, or requisitioning than by acquiring property. The same remark applies, with some nuances, to the satisfaction of the complex needs of the administration. But the difficult adaptation to changing needs and the precariousness that characterizes a large number of these legal techniques presents the risk of a certain loss of control, which can undermine continuity, mutability, "quality" and Performance "of the public service to which the leased asset is assigned. Consequently, public law is called upon to react. A unified legal regime could be applied to all property used by the administration, whatever its owner, in the context of the implementation of a public service activity. These rules would aim at making the use inviolable, apart from the legal instrument on which the exercise of the right of use or enjoyment by the public person is based

Le critère du service public dans la qualification du contrat administratif

International audienceDes incertitudes persistante