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Yang, Bo. "Analyses bioinformatiques et classements consensus pour les données biologiques à haut débit". Thesis, Paris 11, 2014. http://www.theses.fr/2014PA112250/document.
Pełny tekst źródłaIt is thought to be more and more important to solve biological questions using Bioinformatics approaches in the post-genomic era. This thesis focuses on two problems related to high troughput data: bioinformatics analysis at a large scale, and development of algorithms of consensus ranking. In molecular biology and genetics, RNA splicing is a modification of the nascent pre-messenger RNA (pre-mRNA) transcript in which introns are removed and exons are joined. The U2AF heterodimer has been well studied for its role in defining functional 3’ splice sites in pre-mRNA splicing, but multiple critical problems are still outstanding, including the functional impact of their cancer-associated mutations. Through genome-wide analysis of U2AF-RNA interactions, we report that U2AF has the capacity to define ~88% of functional 3’ splice sites in the human genome. Numerous U2AF binding events also occur in other genomic locations, and metagene and minigene analysis suggests that upstream intronic binding events interfere with the immediate downstream 3’ splice site associated with either the alternative exon to cause exon skipping or competing constitutive exon to induce inclusion of the alternative exon. We further build up a U2AF65 scoring scheme for predicting its target sites based on the high throughput sequencing data using a Maximum Entropy machine learning method, and the scores on the up and down regulated cases are consistent with our regulation model. These findings reveal the genomic function and regulatory mechanism of U2AF, which facilitates us understanding those associated diseases.Ranking biological data is a crucial need. Instead of developing new ranking methods, Cohen-Boulakia and her colleagues proposed to generate a consensus ranking to highlight the common points of a set of rankings while minimizing their disagreements to combat the noise and error for biological data. However, it is a NP-hard questioneven for only four rankings based on the Kendall-tau distance. In this thesis, we propose a new variant of pivot algorithms named as Consistent-Pivot. It uses a new strategy of pivot selection and other elements assignment, which performs better both on computation time and accuracy than previous pivot algorithms
Mersch, Marjorie. "Analyse de la méthylation de l'ADN par séquençage haut-débit chez la Poule". Thesis, Toulouse, INPT, 2018. http://www.theses.fr/2018INPT0107/document.
Pełny tekst źródłaAnticipating the impact of environmental changes (on climate and feed) is a crucial issue for livestock production systems, including poultry. The influence of the environment on phenotypes is partly mediated by epigenetic phenomena, including DNA methylation, which may be involved in the regulation of gene expression. These mechanisms do not affect the DNA sequence but can be inherited by mitosis or meiosis. The interactions between epigenomes and gene expression are increasingly being studied in animal models and in plants. However, the mechanisms of regulation of genome expression through DNA methylation are relatively unknown in birds. This thesis work is based on two experimental devices realized in chicken aiming to characterize the methylome by high-throughput sequencing. The methylation patterns across the genome, and their link with expression, were first established by whole-genome bisulfite sequencing (WGBS) in whole embryos, following a reduced representation bisulfite sequencing (RRBS) from hypothalamus of adults. To date, no specific chicken RRBS study has been published. These two analyses were carried out by developing an optimized bioinformatics pipeline, available for scientific community. Overall, the pattern of methylation in chicken is like those in mammals: CpG islands - dinucleotides CG-rich regions which are often poorly methylated, and which are found mainly in the promoter regions of the genome - are generally poorly methylated in promoters on WGBS and RRBS data. Embryo methylome analyses confirmed the absence of a dose-compensation phenomenon on sex chromosomes, or the presence of a hypermethylated region on the Z chromosome. The analyses of RRBS data revealed an overall hypermethylation of CGs across the genome, suggesting a methylation response to environmental stress. From the analysis of WGBS data, we found that the level of methylation in promoters was negatively correlated with the expression of the associated gene. For the first time, a specific allele methylation was also detected between chicken lines whose frequency is comparable to that observed in humans. On the RRBS data, preliminary results of the methylome response to environmental stresses showed the complex nature of this relationship. The use of a low-energy diet would led to greater mobilization of body fat, while individuals with heat stress had a lighter body weight. Integrating these data with phenotypic measurements would allow to link methylation and environment. Beyond the fundamental aspect of this thesis, the method developed in this work could be applied to livestock systems to breed animals better adapted to a changing environment, by improving production traits
Schoenauer, Sebag Alice. "Développement de méthodes pour les données de cribles temporels à haut contenu et haut débit : versatilité et analyses comparatives". Thesis, Paris, ENMP, 2015. http://www.theses.fr/2015ENMP0035/document.
Pełny tekst źródłaBiological screens test large sets of experimental conditions with respect to their specific biological effect on living systems. Technical and computational progresses have made it possible to perform such screens at a large scale - up to hundreds of thousands of experiments. Live cell imaging is an excellent tool to study in detail the consequences of chemical perturbation on a given biological process. However, the analysis of live cell screens demands the combination of robust computer vision methods, efficient statistical methods for the detection of significant effects and robust procedures for quality control. This thesis addresses these challenges by developing analytical methods for the analysis of High Throughput time-lapse microscopy screening data. The developed frameworks are applied to publicly available HCS data, demonstrating their applicability and the benefits of HCS data remining. The first multivariate workflow for the study of single cell motility in such large-scale data is detailed in Chapter 2. Chapter 3 presents this workflow application to previously published data, and the development of a new distance for drug target inference by in silico comparisons of parallel siRNA and drug screens. Finally, chapter 4 presents a complete methodological pipeline for performing HT time-lapse screens in Environmental Toxicology
Teissandier, Aurélie. "Analyses bioinformatiques de la régulation des éléments transposables chez les mammifères". Thesis, Sorbonne université, 2018. http://www.theses.fr/2018SORUS251/document.
Pełny tekst źródłaTransposable elements are DNA sequences that have the ability to move in the genome. They can modify the architecture and the regulation of the genome, and be implicated in different pathological, congenital or acquired disorders. The transposon analysis with sequencing data is the first choice method to understand their biology. My thesis work was dedicated to this question using real and simulated data. In a first research axis, using a cellular system to modulate DNA methylation levels, we revealed that different repressive chromatin modifications ensure the silencing of transposable elements when DNA methylation is lost. In a second axis, using a random mutagenesis strategy, we discovered a new DNA methyltransferase, specialized in the methylation of young transposons during spermatogenesis. However, the analysis of transposons in sequencing datasets is a bioinformatic challenge because of the repeated nature of transposable elements. Eventually, in a third axis, using a simulation strategy applied to the mouse and the human genomes, I systematically compared different alignment and quantification tools. I was able to draw recommendations for the analysis of transposons and to reveal the limits in detecting specific transposons families
Teissandier, Aurélie. "Analyses bioinformatiques de la régulation des éléments transposables chez les mammifères". Electronic Thesis or Diss., Sorbonne université, 2018. http://www.theses.fr/2018SORUS251.
Pełny tekst źródłaTransposable elements are DNA sequences that have the ability to move in the genome. They can modify the architecture and the regulation of the genome, and be implicated in different pathological, congenital or acquired disorders. The transposon analysis with sequencing data is the first choice method to understand their biology. My thesis work was dedicated to this question using real and simulated data. In a first research axis, using a cellular system to modulate DNA methylation levels, we revealed that different repressive chromatin modifications ensure the silencing of transposable elements when DNA methylation is lost. In a second axis, using a random mutagenesis strategy, we discovered a new DNA methyltransferase, specialized in the methylation of young transposons during spermatogenesis. However, the analysis of transposons in sequencing datasets is a bioinformatic challenge because of the repeated nature of transposable elements. Eventually, in a third axis, using a simulation strategy applied to the mouse and the human genomes, I systematically compared different alignment and quantification tools. I was able to draw recommendations for the analysis of transposons and to reveal the limits in detecting specific transposons families
François, Nicolas. "Analyse d'interactions moléculaires à haut débit". Paris 5, 2010. http://www.theses.fr/2010PA05S003.
Pełny tekst źródłaThis thesis tackles the locks held by emerging technologies for analyzing high throughput molecular interactions, allowing to acquire continuous measurements upon parallel interactions. Two technologies are promising: the target marking by fluorescence, which is a proven technique in biology; and the surface plasmon resonance (SPR), requiring no labeling of molecules. This thesis suggests an original automatic approach for image analysis of high throughput interactions, applicable to both fluorescence and SPR methods. From a mathematical model based upon common characteristics describing experimental studies, it combines 2D and 3D geodesic operators, classification and constraints of physical behavior. Coupled with the experimental protocol specific to each of the high throughput methods, involving calibrations and spatiotemporal filtering of noise, it ultimately provides a complete technology for the analysis of high throughput data. Assessed qualitatively and quantitatively on a data set, both synthetic and experimental, it confirms our expectations regarding the sensitivity of detection systems with high throughput, even at low concentrations of target. The characteristics of the interactions studied thus estimated were compared with those obtained by reference methods, or theoretical values. The results are in agreement, validating that the use of high throughput techniques for analyzing molecular interactions and the methodology developed for the exploitation of such data. This study thus opens new perspectives on the use of these technologies as well as part of research in biology, in a clinical setting to aid diagnosis or gene therapy
Aubert, Julie. "Analyse statistique de données biologiques à haut débit". Thesis, Université Paris-Saclay (ComUE), 2017. http://www.theses.fr/2017SACLS048/document.
Pełny tekst źródłaThe technological progress of the last twenty years allowed the emergence of an high-throuput biology basing on large-scale data obtained in a automatic way. The statisticians have an important role to be played in the modelling and the analysis of these numerous, noisy, sometimes heterogeneous and collected at various scales. This role can be from several nature. The statistician can propose new concepts, or new methods inspired by questions asked by this biology. He can propose a fine modelling of the phenomena observed by means of these technologies. And when methods exist and require only an adaptation, the role of the statistician can be the one of an expert, who knows the methods, their limits and the advantages.In a first part, I introduce different methods developed with my co-authors for the analysis of high-throughput biological data, based on latent variables models. These models make it possible to explain a observed phenomenon using hidden or latent variables. The simplest latent variable model is the mixture model. The first two presented methods constitutes two examples: the first in a context of multiple tests and the second in the framework of the definition of a hybridization threshold for data derived from microarrays. I also present a model of coupled hidden Markov chains for the detection of variations in the number of copies in genomics taking into account the dependence between individuals, due for example to a genetic proximity. For this model we propose an approximate inference based on a variational approximation, the exact inference not being able to be considered as the number of individuals increases. We also define a latent-block model modeling an underlying structure per block of rows and columns adapted to count data from microbial ecology. Metabarcoding and metagenomic data correspond to the abundance of each microorganism in a microbial community within the environment (plant rhizosphere, human digestive tract, ocean, for example). These data have the particularity of presenting a dispersion stronger than expected under the most conventional models (we speak of over-dispersion). Biclustering is a way to study the interactions between the structure of microbial communities and the biological samples from which they are derived. We proposed to model this phenomenon using a Poisson-Gamma distribution and developed another variational approximation for this particular latent block model as well as a model selection criterion. The model's flexibility and performance are illustrated on three real datasets.A second part is devoted to work dedicated to the analysis of transcriptomic data derived from DNA microarrays and RNA sequencing. The first section is devoted to the normalization of data (detection and correction of technical biases) and presents two new methods that I proposed with my co-authors and a comparison of methods to which I contributed. The second section devoted to experimental design presents a method for analyzing so-called dye-switch design.In the last part, I present two examples of collaboration, derived respectively from an analysis of genes differentially expressed from microrrays data, and an analysis of translatome in sea urchins from RNA-sequencing data, how statistical skills are mobilized, and the added value that statistics bring to genomics projects
Pham, Nguyen Phuong. "Analyses génomiques comparatives de souches de Brevibacterium et étude de leurs interactions biotiques avec Hafnia alvei dans un fromage modèle". Electronic Thesis or Diss., Université Paris-Saclay (ComUE), 2018. http://www.theses.fr/2018SACLA035.
Pełny tekst źródłaThe objective of this study was to better understand the molecular mechanisms of microbial adaptation to the cheese habitat by functional genomic approaches using Brevibacterium as a model microorganism. This bacterium is widely used for the manufacturing of cheese but its growth on the cheese surface is sometimes difficult to control.Comparative genomic analysis of 23 Brevibacterium strains, including 12 strains isolated from cheeses, revealed differences in genetic determinants involved in the growth on the cheese surface. Some of them are correlated to strain phylogeny and others are the result of gene transfers, especially those involved in iron acquisition and bacteriocin biosynthesis. We identified genomic islands corresponding to transfers of genes involved in iron acquisition between cheese-associated Brevibacterium strains and cheese-associated strains belonging to other genera. We also detected a conjugative transposon encoding bacteriocin production, which is present in cheese-associated Brevibacterium strains as well as in a cheese-associated Corynebacterium strain.Functional study of biotic interactions between Brevibacterium and Hafnia alvei, another cheese-ripening bacterium, was performed in a model cheese developed in this study. By coupling microbial, biochemical and transcriptomic (RNA-seq) analyses, we revealed several interaction mechanisms between these bacteria. These concern, in particular, iron acquisition, proteolysis, lipolysis, sulfur metabolism and D-galactonate catabolism. Our findings suggest that in the mutualistic relationship between some Brevibacterium strains and H. alvei, the latter stimulates Brevibacterium growth by the secretion of siderophores, which can be used by Brevibacterium to capture iron more efficiently. In return, Brevibacterium secretes lipases and proteases, which degrade cheese caseins and triglycerides into energetic substrates that stimulate H. alvei growth. This type of interaction is interesting to consider in the formulation of ripening cultures because it results in a better ability of all partners to colonize the cheese, and thus to generate the desired technological properties
Mirat, Olivier. "Analyse haut-débit du comportement spontané d'un organisme modèle " simple "". Phd thesis, Université René Descartes - Paris V, 2013. http://tel.archives-ouvertes.fr/tel-00881755.
Pełny tekst źródłaDionnet, Eugénie. "Exploration de l'hétérogénéité mutationnelle et de ses conséquences pathologiques dans les myopathies : analyses des mécanismes et développement d'outils thérapeutiques". Thesis, Aix-Marseille, 2016. http://www.theses.fr/2016AIXM5046/document.
Pełny tekst źródłaNowadays, diagnosis and pathomechanisms of genetic disorders remain difficult to explore. There are actually more than 200 forms of myopathies, mostly genetics, even if the culprit gene is not always identified. However, even when the causative gene is known, it often remains diagnostic issues because of clinical and genetic heterogeneity and wide mutational spectrum. The lack of genetic information affects patients cares and impairs the development of new therapeutic tools. My thesis was conducted in order to extend these elements: I have shown that a new gene may be involved in facio-scapulo-humeral dystrophy; I have improved calpainopathie’s diagnosis by studying the impact of missense mutations on RNA splicing; I have also analyzed how proteins contributed to calcium entry in the cell. Finally, I contributed with a new therapeutic tools for dysferlinopathies
Drouard, Joeffrey. "Analyse économique du marché du haut débit : contributions théoriques et empiriques". Phd thesis, Télécom ParisTech, 2010. http://pastel.archives-ouvertes.fr/pastel-00543896.
Pełny tekst źródłaStefic, Karl. "Diversité du Virus de l'Immunodéficience Humaine 1 (VIH-1) et évolution de la sensibilité aux anti-corps neutralisants : analyses au niveau individuel et au niveau populationnel". Thesis, Tours, 2018. http://www.theses.fr/2018TOUR3316.
Pełny tekst źródłaNeutralizing antibodies exert a selection pressure that drives HIV-1 evolution, playing a major role in its diversification. We were interested in the relationship between the genetic diversity of the virus and its neutralization by antibodies at both the individual and the populational levels. At the individual level, viral populations with distinct genetic properties have been observed in the central nervous system in about half of the subjects infected with HIV-1. We studied this phenomenon, termed compartmentalization. Our results suggest that the selection pressure by neutralizing antibodies is not responsible for the evolution pathway of neurotropic variants in the CSF. We also observed specific features for these neurotropic variants. In the second part of this work, we evaluated the sensitivity to broadly neutralizing antibodies of recently transmitted CRF02_AG viruses isolated in France. We observed an increased resistance to some monoclonal antibodies, which was positively correlated with the diversification of the viruses during the study period. This is in line with the hypothesis of the repercussion of the selection pressure within individuals towards a greater resistance of HIV-1 at the populational level
Pham, Nguyen Phuong. "Analyses génomiques comparatives de souches de Brevibacterium et étude de leurs interactions biotiques avec Hafnia alvei dans un fromage modèle". Thesis, Université Paris-Saclay (ComUE), 2018. http://www.theses.fr/2018SACLA035/document.
Pełny tekst źródłaThe objective of this study was to better understand the molecular mechanisms of microbial adaptation to the cheese habitat by functional genomic approaches using Brevibacterium as a model microorganism. This bacterium is widely used for the manufacturing of cheese but its growth on the cheese surface is sometimes difficult to control.Comparative genomic analysis of 23 Brevibacterium strains, including 12 strains isolated from cheeses, revealed differences in genetic determinants involved in the growth on the cheese surface. Some of them are correlated to strain phylogeny and others are the result of gene transfers, especially those involved in iron acquisition and bacteriocin biosynthesis. We identified genomic islands corresponding to transfers of genes involved in iron acquisition between cheese-associated Brevibacterium strains and cheese-associated strains belonging to other genera. We also detected a conjugative transposon encoding bacteriocin production, which is present in cheese-associated Brevibacterium strains as well as in a cheese-associated Corynebacterium strain.Functional study of biotic interactions between Brevibacterium and Hafnia alvei, another cheese-ripening bacterium, was performed in a model cheese developed in this study. By coupling microbial, biochemical and transcriptomic (RNA-seq) analyses, we revealed several interaction mechanisms between these bacteria. These concern, in particular, iron acquisition, proteolysis, lipolysis, sulfur metabolism and D-galactonate catabolism. Our findings suggest that in the mutualistic relationship between some Brevibacterium strains and H. alvei, the latter stimulates Brevibacterium growth by the secretion of siderophores, which can be used by Brevibacterium to capture iron more efficiently. In return, Brevibacterium secretes lipases and proteases, which degrade cheese caseins and triglycerides into energetic substrates that stimulate H. alvei growth. This type of interaction is interesting to consider in the formulation of ripening cultures because it results in a better ability of all partners to colonize the cheese, and thus to generate the desired technological properties
Hamza, Tasnim. "Communications optiques sous-marines : transmission longue-portée haut débit et analyse des performances". Thesis, Ecole centrale de Marseille, 2017. http://www.theses.fr/2017ECDM0002.
Pełny tekst źródłaToday we are witnessing a growing need to high-rate data transmission in underwater missions in a wide range of application areas. Within this context, traditional cable- or fiber-based communications imply costly deployments with very limited flexibility, and the conventional acoustic communications offer very low operational performance. Recently, with the development of small and low-cost optoelectronic components and devices, it has become feasible to realize small and compact wireless optical communication transceivers providing unprecedentedly high transmission rates and energy efficiency. However, there still remain several shortcomings of this technology, in particular to attain high data rates over relatively long communication ranges. In order to overcome some of these limitations, this PhD thesis considers the use of advanced optoelectronic components and signal processing techniques in order to improve the performance of underwater wireless optical communication (UWOC) links. In this view, after studying the effect of solar background noise on the performance of these links, we investigate the use of the recent promising Silicon photo-multipliers (SiPMs) in UWOC receivers and study the corresponding system performance in different conditions of water turbidity. We also propose efficient transmission solutions, mainly based on pulse amplitude modulation and frequency domain equalization in order to surpass the bandwidth limitation of the emitters and SiPMs to allow high rate data transmission. The benefits of the proposed solutions are further validated through experimental measurements
Torre, Cyril. "Analyse haut-débit des complexes transcriptionnels de la β-caténine dans le foie murin". Thesis, Paris 11, 2011. http://www.theses.fr/2011PA11T004/document.
Pełny tekst źródłaThe Wnt/β-catenin pathway is involved in proliferation and cell fate control and regulatesdevelopmental stages as well as adult tissue homeostasis. Our team has previously shown that aberrantB-catenin signaling induced Hepatocellular Carcinoma (HCC) development, whereas physiologicalactivation in a subpopulation of adult liver hepatocytes (pericentral hepatocytes) patterns liverzonation. This hepatic zonation can be considered as hepatocytes terminal differenciation.My thesis aimed to identify key molecular determinants allowing diversity upon β-catenin activation.I took advantage of genetically engineered mice models of activation or inactivation of β-catenin,developped in the laboratory. Using hepatocytes obtained from these models I identified β-catenin andTcf4, that I previously identifed as the main effector of nuclear β-catenin in liver, binding sites byChIp-seq (Chromatin Immunoprecipitation followed by high-throughput sequencing). Couplingbinding site localization to transcriptomic and chromatin accessibility studies allowed to identifychromatin structure and tissue specific transcription factor HNF4A as key modulators of β-cateninsignaling in the liver and therefore modulators of metabolic zonation. Indeed, β-catenin negativelyregulates Hnf4a target genes. This negative control exerts essentially via protein interactions. Wepropose that β-catenin and Hnf4a cooperates to ensure terminal hepatic differenciation.I also searched for nuclear β-catenin partners by co-immunoprecipitation followed by massspectrometry. This approach revealed many splicing factors as beta-catenin partners. RNA seqanalysis revealed a possible direct regulation of splicing of SL39A14 and NDRG2 genes.Finally we tried to understand the proliferative role of β-catenin during liver regeneration. Wedemonstrated a complex and partially autocrine role of B-catenin. We defined CyclinD1 and thegrowth factor Tgfa as β-catenin direct targets in the liver. These latest results also imply a functionnaldialog between the β-catenin pathway and Tgfa-Egf/Egfr/Erk signalisation cascade to allowhepatocytes proliferation
Edimo, Paul. "Analyse de frontière stochastique pour l'optimisation des plans en curiethérapie haut débit de dose". Master's thesis, Université Laval, 2018. http://hdl.handle.net/20.500.11794/30683.
Pełny tekst źródłaBrachytherapy is a special modality of radiotherapy for cancerous tissues treatment. Unlike external radiotherapy, this form of radiation therapy modality uses sealed radiation sources positioned permanently or temporarily within (or close to) the treatment volume. Brachytherapy treatment modality has benefited from technological advances such as the use of remote afterloading units and the development of new dose optimization algorithms that led to the improvement of treatment plans quality. However, the treatment planning process, regardless of the optimization algorithm used for dose calculation in the treatment planning system (TPS), still requires a strong interaction between the planner and the TPS. This strong interaction not only increases the planning time, but also often leads to final plans whose quality depends on the planner’s judgment, as well as planner’s experience. The goal of the current project was to develop models for the optimization of the quality of high dose rate prostate brachytherapy plans, based on patient’s specific geometric parameters, using stochastic frontier analysis, a method of economic modeling. Geometric parameters involved in the modeling process are the volume of structures of interest such as the clinical target volume (CTV) and organs at risk (OARs); the Hausdorff distance between CTV and OARs, and a third parameter measuring the degree of non-parallelism of catheters within the prostate. The built models are expected to be helpful in the treatment planning process by predicting dosimetric parameters values attainable at the starting point of the treatment planning. They will provide valuable indications in advance, on the level of dose reduction to OARs, as well as, the target volume coverage achievable. Models were built for dosimetric parameters of interest analyzed in the clinic for clinical validation of plans for each structure (prostate, bladder, rectum and urethra). The modelling results based on a dataset of 495 plans show that the developed models can be helpful to assist planner in the optimization process based on the geometric parameters profile of each plan, thus minimizing the impact of the judgment and the planner’s experience on the final quality plan. Furthermore, their use can be extended as an accurate means for selecting optimized plans for a knowledge-based study. However, further research is required in order to investigate others geometric parameters, as well as, for the clinical benchmarking the performance of the developed models before their implementation in a clinical setting.
Le, Pipec Mathieu. "Analyse d'une filière d'interconnexion adaptée aux systèmes de transmissions à haut débit par fibres optiques". Nantes, 2007. http://archive.bu.univ-nantes.fr/pollux/show.action?id=9bf42af7-1aed-4b46-a757-407ce4b059ad.
Pełny tekst źródłaThe main consequence of rising data rates in high density optical fibre telecommunications systems is the need for ever increasing component integration in both receiver and transmitter front ends. This observation has governed the work of this thesis which is devoted to helping the designer to make the right choice in the key area of interconnection technologies and to propose design rules for implementing these technologies. The first two chapters of this thesis describe the architectures of commonly deployed high data rate optical fibre systems. The principal components used in these systems are also presented as are their main characteristics. The second part concerns the selection of the right interconnection technology taking into consideration the system performances required and the constraints imposed by the necessities of component integration. A theoretical electromagnetic study of appropriate propagating structures is backed up by measurement of these structures and confirms the interest of conductor backed coplanar waveguide structures for this application. The final part of this work introduces the notion of integration with regard to a classical component such as a packaged Mach-Zehnder modulation driver and the resulting influence on the overall optical fibre system performance as measured by eye diagram and Bit Error Ratio. The analysis of the results of the electromagnetic simulation of the proposed structures allows us to propose equivalent circuit models of the transitions developed, which can be readily integrated into circuit simulators
Hurel, Julie. "Détection d'organismes génétiquement modifiés (OGM) inconnus par analyse statistique de données de séquençage haut débit". Thesis, Rennes 1, 2020. http://www.theses.fr/2020REN1B027.
Pełny tekst źródłaThe European Union has adopted a very restrictive policy towards the dissemination and use of genetically modified organisms (GMOs), whose use in food is not well accepted by consumers. Although a maximum threshold exists for a food to be labelled "GM-free", only known GMOs are easily detectable. A GMO consists mainly of a host genome and a sequence inserted by a non-natural process that confers a particular property on the organism, such as resistance to certain diseases. In recent years, GMOs with an inserted sequence that is not known have been produced that are not detectable by approaches used until now (PCR-type). Hence the need to propose a tool for the detection of unknown GMOs, the subject of this thesis, based on recent advances in terms of high-throughput sequencing. Statistically, each organism has a specific frequency of nucleotide use in its genome. Any introduction of foreign genetic material will locally alter the nucleotide use frequencies in that region, resulting in different nucleotide use frequencies compared to those of the host organism. Based on this assertion, an unknown GMO detection tool has been developed from bacterial sequencing data when the GMO results from the insertion of a foreign gene, the truncation or fusion of a gene that may belong to the host genome. The tool has been tested on 4 GMO bacterial genomes, 7 wild bacterial genomes and 42 synthetic bacterial genomes. The results demonstrate the effectiveness of the method developed by presenting only one false positive gene and identifying more than 99% of the genes of GMO inserts
Da, Silva Ophélie. "Structure de l'écosystème planctonique : apport des données à haut débit de séquençage et d'imagerie". Electronic Thesis or Diss., Sorbonne université, 2021. http://www.theses.fr/2021SORUS183.
Pełny tekst źródłaPlanktonic organisms are key actors in oceanic ecosystems, which support trophic networks and play a major role in biogeochemical cycles and climate regulation. While the spatio-temporal distribution of planktonic diversity can be investigated at several levels, from the gene to the ecosystem, identifying the underlying mechanisms is challenging. Indeed, the structure of diversity results from different evolutionary and ecological processes that can act simultaneously. Since the beginning of the 21st century, the oceanic environment has been increasingly monitored. Numerous observation platforms have been deployed, leading to the acquisition of a large amount of data for multiple environmental characteristics. At the same time, technologies for studying living organisms have been developed. Thus, an unprecedented sampling of planktonic organisms has taken place. In particular, high-throughput sequencing and imaging data provide molecular, taxonomic and functional information at several biological levels. The objective of this thesis was to explore the structure of planktonic ecosystems using high-throughput sequencing and imaging data. Coupling with environmental data could contribute to a better understanding of the spatial distribution of planktonic diversity, from species to communities. In the first part, the genetic diversity of protists was studied at the species level. The hypothesis was that metagenomics could provide access to the poorly characterized spatial organization of the intraspecific protist genetic diversity, as well as to the mechanisms underlying it. In a second part, the link between genetic diversity and functional diversity was explored. Transparency was targeted. This functional trait is little explored at the community level and its molecular basis is poorly identified. A data-driven approach allowed this trait to emerge from imaging data, leading to the exploration of its biogeography and molecular basis. In the last part, the high potential of complementarity between sequencing, imaging and environmental datasets was explored, in order to highlight the multi-scale structure of the planktonic ecosystem and to identify its global structure. Finally, all the results were discussed to highlight the contributions that these data can provide to the understanding of planktonic ecosystems, as well as the limitations they can face
Karaouzene, Thomas. "Bioinformatique et infertilité : analyse des données de séquençage haut-débit et caractérisation moléculaire du gène DPY19L2". Thesis, Université Grenoble Alpes (ComUE), 2017. http://www.theses.fr/2017GREAS041/document.
Pełny tekst źródłaIn the last decade, the investigations of genetic diseases have been revolutionized by the rise of high throughput sequencing (HTS). Thanks to these new techniques it is now possible to analyze the totality of the coding sequences of an individual (exome sequencing) or even the sequences of his entire genome or transcriptome.The understanding of a pathology and of the genes associated with it now depends on our ability to identify causal variants within a plethora of technical artifact and benign variants.HTS is expected to be particularly useful in the field infertility as this pathology is expected to be highly genetically heterogeneous and only a few genes have so far been associated with it. My thesis focuses on male infertility and is divided into two main parts: HTS data analysis of infertile men and the molecular characterization of a specific phenotype, globozoospermia.Several thousands of distinct variants can be identified in a single exome, thereby using effective informatics is essential in order to obtain a short and actionable list of variants. It is for this purpose that I developed a HTS data analysis pipeline performing successively all bioinformatics analysis steps: 1) reads mapping along a reference genome, 2) genotype calling, 3) variant annotation and 4) the filtering of the variants considered as non-relevant for the analysis. Performing all these independent steps within a single pipeline is a good way to calibrate them and therefore to reduce the number of erroneous calls. This pipeline has been used in five studies and allowed the identification of variants impacting candidate genes that may explain the patients’ infertility phenotype. All these variants have been experimentally validated using Sanger sequencing.I also took part in the genetic and molecular investigations which permitted to demonstrate that the absence of the DPY192 gene induces male infertility due to globozoospermia, the presence in the ejaculate of only round-headed and acrosomeless spermatozoa. Most patients with globozoospermia have a homozygous deletion of the whole gene. I contributed to the characterization of the mechanisms responsible for this recurrent deletion, then, using Dpy19l2 knockout (KO) mice, I realized the comparative study of testicular transcriptome of wild type and Dpy19l2 -/- KO mice. This study highlighted a dysregulation of 76 genes in KO mice. Among them, 23 are involved in nucleic acid and protein binding, which may explain acrosome anchoring defaults observed in the sperm of globozoospermic patients.My work allowed a better understanding of globozoospermia and the development of a HTS data analysis pipeline. The latter allowed the identification of more than 15 human gametogenesis genes involved in different infertility phenotypes
Omnès, Nathalie. "Analyse d'outils de contrôle de la qualité de service dans les réseaux de paquets haut débit". Rennes 1, 2001. http://www.theses.fr/2001REN10134.
Pełny tekst źródłaLabbé, Cyril. "Analyse de performances pour les réseaux à haut débit : modélisation et émulation sur une architecture reconfigurable". Grenoble INPG, 1999. http://www.theses.fr/1999INPG0071.
Pełny tekst źródłaMuller, Jean. "Analyse du cytosquelette par des approches bioinformatiques à haut débit de génomique comparative et de transcriptomique". Université Louis Pasteur (Strasbourg) (1971-2008), 2006. https://publication-theses.unistra.fr/public/theses_doctorat/2006/MULLER_Jean_2006.pdf.
Pełny tekst źródłaThe work of my PhD focuses on applications of bioinformatics methodologies and high throughput analysis techniques to study the cytoskeleton. My work also highlights several novel bioinformatics developments allowing the study of highly complex biological systems like the cytoskeleton. In the first part, comparative genomics and particularly phylogenetic profiling methods are discussed. ComIcs, a new tool, was developed to automatically establish the phylogenetic profiles for the complete set of cytoskeleton genes in 41 eukaryotic organisms. Results revealed several major limitations of the method linked either to highly similar protein families or the lack of complete proteomes for some organisms. Some of these issues were addressed by an in depth analysis of actin and the Actin-Related Proteins family. This led to the implementation of ARPAnno, a web server dedicated to the identification of protein sequences similar to actin. In the second part, I described the development of a new dedicated microarray, named Actichip, to monitor the expression profiles of cytoskeleton genes. The development of this dedicated tool required the implementation of CADO4MI, a new program for the design of specific oligonucleotide probes for microarrays. The strategy and a first application of Actichip are presented in this part
Dégardin, Virginie. "Analyse de la faisabilité d'une transmission de données haut débit sur le réseau électrique basse tension". Lille 1, 2002. https://pepite-depot.univ-lille.fr/LIBRE/Th_Num/2002/50376-2002-269-270.pdf.
Pełny tekst źródłaMolnar, Jean-Marc. "Infrastructures de réseaux haut débit et mobile de nouvelle génération, développement économique local, inégalités territoriales". Paris, CNAM, 2003. http://www.theses.fr/2003CNAM0462.
Pełny tekst źródłaThe development of broadband and mobile telephone is studied for the last two decades of the XXth century in the French metropolitan area. Three infrastructures levels are used as observatory levels to discern structuring effects of telecommunication networks on territorial activities : physical level, consumption level and legal administrative level. The analysis shows that, if a division between well and poor-industrialized French regions has traditionally been perceived in the three decades following World War II, such a regional partition can also be distinguished for high performance and mobile networks after 1980. A spatial analysis and a set of economic and sectoral indicators reveal several oppositions, particularly a north-south territorial division
Pampouille, Eva. "Analyse haut-débit du déterminisme de défauts musculaires impactant la qualité de la viande chez le poulet". Thesis, Tours, 2019. http://www.theses.fr/2019TOUR4010.
Pełny tekst źródłaPoultry industry is facing muscular defects which that impair chicken meat quality. Genetic and genomic studies were carried out in addition to histological measuremnets to better understand the etiology of these defects and to contribute to the development of new indicators useful for diagnosis and selection. Studies focused on two complementary genetic models : 1) two divergent chicken lines selectied on breast meat ultimate pH and 2) a line with strong muscular development more severely affected by the defects, qwhich was studied in comparison with a slow-growing strain free from lesions. The thesis helped to describe the metabolic and structural changes observed in case of severe myopathies. It also led to the identification of the first QTL regions controlling muscular defects in chicken and to the establishment of a set of genes correlated with histological measurements of myopathies that will serve after validation as tool for selection and breeding
Guignard, Léo. "Analyse quantitative de la morphogenèse animale : de l'imagerie laser haut-débit à l'embryon virtuel chez les ascidies". Thesis, Montpellier, 2015. http://www.theses.fr/2015MONTS048/document.
Pełny tekst źródłaAscidian embryos develop with stereotyped and evolutionarily conserved invariant cell lineages to produce in a few hours or days tadpole larvae with a small number of cells. They thus provide an attractive framework to describe with cellular resolution the developmental program of a whole organism. During my PhD, I developed a quantitative approach to describe the evolution of embryonic morphologies during the development of the ascidian Phallusia mammillata. I then used this approach to systematically characterize in detail the logic of cell fate induction events. To quantitatively characterize cell behaviors during embryogenesis, we used multi-angle light-sheet microscopy to image with high spatio-temporal resolution entire live embryos with fluorescently labeled plasma membranes. To extract biological information from this imaging dataset, I then developed a conceptually novel automated method for 4D cell segmentation, ASTEC. Applied to a Phallusia mammillata embryo imaged for 6 hours between the 64-cell and the initial tailbud stages, this method allows the accurate tracking and shape analysis of 1030 cells across 640 cell divisions. The resulting 4D digital embryo can be formalized as a dynamic graph, in which cells are represented by nodes, linked within a time point by edges that represent their spatial neighborhood, and between time points by temporal edges describing cell lineages.Based on this quantitative digital representation, we systematically identified cell fate specification events up to the late gastrula stage. Computational simulations revealed that remarkably simple rules integrating measured cell-cell contact areas with boolean spatio-temporal expression data for extracellular signalling molecules are sufficient to explain most early cell inductions. This work suggests that in embryos establishing precise stereotyped contacts between neighboring cells, the genomic constraints for precise gene expression levels are relaxed, thereby allowing rapid genome evolution
Guillemot, Vincent. "Application de méthodes de classification supervisée et intégration de données hétérogènes pour des données transcriptomiques à haut-débit". Phd thesis, Université Paris Sud - Paris XI, 2010. http://tel.archives-ouvertes.fr/tel-00481822.
Pełny tekst źródłaBidaj, Klodjan. "Modélisation du bruit de phase et de la gigue d'une PLL, pour les liens séries haut débit". Thesis, Bordeaux, 2016. http://www.theses.fr/2016BORD0355/document.
Pełny tekst źródłaBit rates of high speed serial links (USB, SATA, PCI-express, etc.) have reached the multi-gigabits per second, and continue to increase. Two of the major electrical parameters used to characterize SerDes Integrated Circuit performance are the transmitted jitter at a given bit error rate (BER) and the receiver capacity to track jitter at a given BER.Modeling the phase noise of the different SerDes components, extracting the time jitter and decomposing it, would help designers to achieve desired Figure of Merit (FoM) for future SerDes versions. Generating white and colored noise synthetic jitter patterns would allow to better analyze the effect of jitter in a system for design verification.The phase locked loop (PLL) is one of the contributors of clock random and periodic jitter inside the system. This thesis presents a method for modeling the PLL with phase noise injection and estimating the time domain jitter. A time domain model including PLL loop nonlinearities is created in order to estimate jitter. A novel method for generating Gaussian distribution synthetic jitter patterns from colored noise profiles is also proposed.The Standard Organizations specify random and deterministic jitter budgets. In order to decompose the PLL output jitter (or the generated jitter from the proposed method), a new technique for jitter analysis and decomposition is proposed. Modeling simulation results correlate well with measurements and this technique will help designers to properly identify and quantify the sources of deterministic jitter and their impact on the SerDes system.We have developed a method, for specifying PLLs in terms of Phase Noise. This method works for any standard (USB, SATA, PCIe, …), and defines Phase noise profiles of the different parts of the PLL, in order to be sure that the standard requirements are satisfied in terms of Jitter
Jané, Palli Pau. "Quantification des affinités PBM/PDZ et de leurs sites modulateurs par des approches expérimentales et informatiques à haut débit". Electronic Thesis or Diss., Strasbourg, 2020. http://www.theses.fr/2020STRAJ051.
Pełny tekst źródłaThis thesis focuses on PDZ domains, a family of globular domains that bind to conserved PDZ-Binding Motifs (called henceforth PBMs) generally situated at the extreme C-terminus of their partner proteins. Domain-motif networks are often modulated by reversible post-translational modifications (PTMs). We used synthetized PBMs to reproduce different conditions, such as a wild-type, acetylation or phosphorylation, addition of extra exosites or residue mimication of PTM in the literature. These peptides were used for interaction studies using the holdup assay, an assay originally developed in our laboratory. We evaluated the impact of diverse modifications of the PBM/PDZ interactions, which led to a global change of the PDZ-binding capability. These results provided quantitative information on the biological effects that such modifications may have in the context of full-length proteins
Lacoste, Deixonne Caroline. "Apport du séquençage haut débit dans l'amélioration de la prise en charge des maladies monogéniques". Thesis, Aix-Marseille, 2016. http://www.theses.fr/2016AIXM5062/document.
Pełny tekst źródłaThe diffusion of Next Generation Sequencing (NGS) technologies induces an important change that modifies molecular diagnostics indications and prompts laboratories to re-think their diagnostic strategies, up-to-now based on Sanger sequencing routine. Several high throughput approaches are available from the sequencing of a gene panel, to a whole exome, or even a whole genome. In all cases, a tremendous amount of data are generated, that have to be filtered, interpreted and analyzed by the use of powerful bioinformatics tools.In part 1, existing strategies and the difficulties and challenges of high-throughput sequencing for molecular diagnosis in genetic diseases are discussed. In part 2, the set up and the technical validation of this diagnostic approach in the Molecular Genetics’ Laboratory of the Timone Hospital in Marseille is presented and illustrated by 3 examples of complex diagnostics solved thanks to NGS. NGS promises to shorten significantly the time of analysis and results reporting, and to expand the number of tested genes. It also promises to increase the proportion of positive diagnoses. Finally, the NGS can identify new variants and new genes involved in human pathology, thus will globally improve patient clinical care
Abboun, Miloud. "Caractérisation et modélisation de transistor bipolaire à double hétérojonction (TBdH) sur InP pour la conception de circuits à haut débit". Paris 11, 2003. http://www.theses.fr/2003PA112112.
Pełny tekst źródłaThe progress in data processing communication systems require circuits with high data rate which are based on high speed transistors with high power. III-V Bipolar Heterojunction Transistors (HBTs) constitute a good trade-off, and more particularly InP based -HBTs. These device are well suited for the development of telecommunications systems with data rates higher than 60 Gbits/s, moreover this technology allows the integration of optoelectronic devices with wavelength ranging between 1,3 mM and 1,55 mM. The renewed interest for these technologies underlines the problems and the constraints related to compact modeling. The work was developed under the frame of a tight collaboration between the CNET Bagneux/OPTO+ and the IEF. The aim of this thesis is the experimental study and the electrical modeling of InP-DHBT. Four self-aligned technologies which differ by the nature of base doping (beryllium or carbon) and by the presence of an indium gradient in the base were studied. For each technology a large number of devices were analyzed and an important mass of experimental data made it possible to obtain the parameters of the model of Gummel-Poon for such devices. These models were then used by circuit designers at OPTO+ for the conception of logic circuits with high debit (multiplexer, circuit of decision, rock-D, driver. . . ). The large data base also made it possible to study the influence of self-heating effects in InP-HBT by an experimental point of view and then by a numerical modeling of Fourier equation. Simulation results allows to find the pathways to reduce self-heating effects in the studied devices. For a better understanding of the physics governing the HBT performance, an experimental analysis at variable temperature was carried out on one of four technologies. Finally, an analysis of sensitivity of the parameters of the model of Gummel-Poon at 300K over the switching time of the differential pairs (CML/ECL technology) was performed: -Delay time t(FF) and charge time R(BB),C(jC) are the two most important intrinsic contributions, -The extraction of many parameters of the model is inaccurate (C(jE), Rc amongst other) and they influences t(FF), then the need of developing reliable approaches to extract these elements is pointed out
Rimbert, Antoine. "Génétique et physiopathologie des dystrophies valvulaires mitrales non-syndromiques". Nantes, 2015. https://archive.bu.univ-nantes.fr/pollux/show/show?id=96c2743a-d81a-40f0-bb36-4e2bce4abe12.
Pełny tekst źródłaMitral Valve Prolapse (MVP) is a common cardiac disease (2. 5% of the general population) and is a leading cause for valve surgery. MVP can be sporadic or familial with a strong genetic background however its genetic background remains poorly understood. Here we aim to identify new causative genes involved in the pathogenesis of familial non-syndromic MVP using Next Generation Sequencing, high throughput genotyping, cellular and animal models. We first applied Whole Exome Sequencing and Identity By Descent analysis to identify genetic variations responsible for MVP in 18 affected families. This approach identified APC, DOCK1, ANK2 and PTPRF as new potential genes involved in key functions of MVP pathogenesis (cytoskeleton remodeling and developmental pathways). Second, we have developed a custom kit to capture and sequence coding regions of 78 genes identified by exome sequencing or their likely implication in valve development and applied it to 272 MVP patients. Among them, we identified four rare ARHGAP24 missense variants which co-segregate with MVP in families. In vitro and in vivo experiments showed that all mutations are loss of function and lead to fibroelastic deficiency (FED) type of MVP. Finally, we applied burden tests to test for a significant enrichment in rare coding variations (minor allele frequency <0. 1%) compare to control individuals. Preliminary results identified enrichment in genes involved in valvulogenesis. This work identifies ARHGAP24 as the first gene for FED type of MVP and suggests APC, DOCK1, ANK2 and PTPRF for Barlow type MVP. All genes target key mechanisms that modify MV homeostasis, valvulogenesis and mechanical stress adapted response
Fraïsse, Christelle. "Génétique de l’adaptation et de la spéciation : théorie et analyse de données de séquençage haut-débit dans le complexe d’espèces Mytilus edulis". Thesis, Montpellier 2, 2014. http://www.theses.fr/2014MON20107/document.
Pełny tekst źródłaGenomes are affected by conflicting selective regimes. This is particularly well illustrated by the concept of semi-permeable barriers to gene flow, as found in the hybrid zones literature. Some genes contribute to the prevention of mixing between differentiated genetic lineages, either because they are involved in adaptation to local environmental conditions, or because they are incompatible with alleles from other genetic lineages. Other parts of the genome are either neutral, or subjected to selection which tends to homogenize the genetic lineages. In the first part of this thesis, models of the evolution of reproductive isolation are presented to explain the isolation patterns observed in experimental hybridizing crosses between incipient species. Using standard models of Dobzhansky-Muller genetic incompatibilities, it is shown that the asymmetry and complexity of incompatibilities are not well explained by there being an “evolutionary sieve”, i.e. a different rate of accumulation between incompatibilities. A complementary approach to quantitative modeling (an extension of Fisher's Geometric Model) then clarifies which conditions of divergence between allopatric lines led to highly deleterious effects in hybrid genotypes. The relative importance of mean levels of fitness epistasis, the distribution of mutation sizes, and the way lineages adapt to new environmental conditions is discussed. The second part of this thesis takes advantage of technical advances in genomics to study the history of speciation and adaptation in a non-model species complex, Mytilus mussels. A statistical method of inferring speciation scenarios is presented. Results show that European mussels experienced a complex history of strict divergence followed by a period of periodic connectivity. In agreement with the concept of semi-permeable barriers to gene flow, it is shown that introgression rates are heterogeneous along the genome. Next, genome scans of differentiation were conducted between pairs of populations of the species complex. The analysis of genetic variation and allele genealogies on a small chromosomal scale allowed to reconstruct the evolutionary history of more than 1000 genomic regions. This analysis reveals that a major cause of intraspecific differentiation is the differential introgression of foreign alleles. Overall, this thesis shows not only that biogeography of speciation, i.e. the temporal and spatial patterns of gene flow, play a major role in our understanding of existing biodiversity, but also its amazing complexity and extent of its impact on genome evolution
Bernard, Elsa. "Etude de l'épissage grâce à des techniques de régression parcimonieuse dans l'ère du séquençage haut débit de l'ARN". Thesis, Paris Sciences et Lettres (ComUE), 2016. http://www.theses.fr/2016PSLEM063/document.
Pełny tekst źródłaThe number of protein-coding genes in a human, a nematodeand a fruit fly are roughly equal.The paradoxical miscorrelation between the number of genesin an organism's genome and its phenotypic complexityfinds an explanation in the alternative natureof splicing in higher organisms.Alternative splicing largely increases the functionaldiversity of proteins encoded by a limitednumber of genes.It is known to be involved incell fate decisionand embryonic development,but also appears to be dysregulatedin inherited and acquired human genetic disorders,in particular in cancers.High-throughput RNA sequencing technologiesallow us to measure and question splicingat an unprecedented resolution.However, while the cost of sequencing RNA decreasesand throughput increases,many computational challenges arise from the discrete and local nature of the data.In particular, the task of inferring alternative transcripts requires a non-trivial deconvolution procedure.In this thesis, we contribute to deciphering alternative transcript expressions andalternative splicing events fromhigh-throughput RNA sequencing data.We propose new methods to accurately and efficientlydetect and quantify alternative transcripts.Our methodological contributionslargely rely on sparse regression techniquesand takes advantage ofnetwork flow optimization techniques.Besides, we investigate means to query splicing abnormalitiesfor clinical diagnosis purposes.We suggest an experimental protocolthat can be easily implemented in routine clinical practice,and present new statistical models and algorithmsto quantify splicing events and measure how abnormal these eventsmight be in patient data compared to wild-type situations
Beye, Mamadou. "Génomique en temps réel appliquée aux isolats bactériens cliniques atypiques". Thesis, Aix-Marseille, 2017. http://www.theses.fr/2017AIXM0558.
Pełny tekst źródłaRapid and accurate diagnosis, characterization and identification of pathogens are essential to guide treatment and detect transmission events or treatments failures. However, the biomedical field is confronted with emerging and re-emerging pathogens. Some of these clinical bacterial strains exhibit specificities concerning the virulence, contagiousness and / or resistance to antibiotics. High-throughput sequencing and comparative analysis of bacterial genomes is a reliable strategy enabling the rapid study of the characteristics of these emerging pathogens. In a short period, not exceeding 20 years, genomics has known a considerable revolution. In effect the introduction of the new high-throughput sequencingtechnologies and the increased concern of the scientist into this field, led to an exponential increase of number of available sequenced bacterial genomes in public databases. Real-time genomics is a strategy consisting on rapid analysis of the genome of a clinical bacterial strain in order to identify the genetic determinants justifying its unusual phenotypic characteristics. Thus, the objectives of this thesis project were: to rapidly exploit whole-genome sequencing data for identification of the virulence or resistance repertoire; to compare genomes from atypical clinical bacteria to those of other bacteria of the same species in order to identify their specific features; to use genomes as a taxonomic tool to rapidly describe the new bacterial species isolated in the laboratory by culturomics approach
Seesao, Yuwalee. "Caractérisation des Anisakidae dans les poissons marins : développement d’une méthode d’identification par séquençage à haut-débit et étude de prévalence". Thesis, Lille 2, 2015. http://www.theses.fr/2015LIL2S043/document.
Pełny tekst źródłaAnisakis, Pseudoterranova, Hysterothylacium and Contracaecum genera, members of the Anisakids family, are nematodes which larvae are recovered from numerous fish and cephalopods species. These larvae may induce digestive and/or allergic pathologies in human being. In France, the consumption of fishery products, mostly raw or undercooked is increasing. This PhD work is part of the research program Fish-Parasites funded by the ANR (ANR-10-ALIA-004). It aimed to assess risks related to fishery products consumption and its main goal was to study the distribution of Anisakids in fishery products.The sampling plan was based on a risk-ranking analysis using data on fishery products consumption, fishing areas and prevalence data from previous work on Anisakids. A total of 1 768 fish from 18 species were collected. All the organs were dissected for parasites isolation. Parasites were identified using two approaches : i) single analysis by Sanger sequencing for organs containing less than 11 nematodes ii) pooled analysis by high throughput sequencing (HTS) for the remaining. The development of numerous tools (database creation with reference sequences, primers design, set up of the sequencing template preparation and development of an automatic analytical pipeline) was necessary for the HTS method set up. From the sequencing results, acquisition and structuring of the prevalence data has been carried out on parasites potentially pathogenic for human being and recovered from commonly consumed fishery products.On 1 768 sampled fish, two species were not parasitized at all: plaice (Pleuronectes platessa) and aquacultured Atlantic salmon (Salmo salar). 43.30 % of the fish were not infected by Anisakids. Concerning infected fish, 28.62% were contaminated in the visceral organs; 22.96% in both visceral organs and fillets and, finally, 5.49% of the fish were infected by Anisakids only in fillets.The five fish species with an elevated prevalence in their fillets were by decreasing values: blue ling (100 %), megrim (70 %), saithe (63 %), monkfish (61 %) and hake (60 %). The most identified Anisakids were: Anisakis simplex, Anisakis pegreffii, Hysterothylacium aduncum, Pseudoterranova krabbeii.Anisakis has been recovered in all the localisations and generally in higher quantities, Contracaecum has mainly been recovered from the liver, Hysterothylacium from the corporal cavity and Pseudoterranova from both fillets and corporal cavity. Anisakis simplex was isolated from all the fishing areas except for the Lion Gulf and it was the genus with the most important number of individuals. The zone of Feroan waters was the region with the most important diversity of Anisakids into a single sampled fish species (blue ling).The multivariate logistic statistical study showed that the fish species and size affect the prevalence of Anisakis and Pseudoterranova in fish fillets.HTS with the PGM™ Ion Torrent proved to be a powerful and innovative tool for the analysis of large numbers of Anisakids samples with low cost, in a shorter time and with a result equivalent to the individual method of Sanger sequencing
Morlot, Jean-Baptiste. "Annotation of the human genome through the unsupervised analysis of high-dimensional genomic data". Thesis, Paris 6, 2017. http://www.theses.fr/2017PA066641/document.
Pełny tekst źródłaThe human body has more than 200 different cell types each containing an identical copy of the genome but expressing a different set of genes. The control of gene expression is ensured by a set of regulatory mechanisms acting at different scales of time and space. Several diseases are caused by a disturbance of this system, notably some cancers, and many therapeutic applications, such as regenerative medicine, rely on understanding the mechanisms of gene regulation. This thesis proposes, in a first part, an annotation algorithm (GABI) to identify recurrent patterns in the high-throughput sequencing data. The particularity of this algorithm is to take into account the variability observed in experimental replicates by optimizing the rate of false positive and false negative, increasing significantly the annotation reliability compared to the state of the art. The annotation provides simplified and robust information from a large dataset. Applied to a database of regulators activity in hematopoiesis, we propose original results, in agreement with previous studies. The second part of this work focuses on the 3D organization of the genome, intimately linked to gene expression. This structure is now accessible thanks to 3D reconstruction algorithm from contact data between chromosomes. We offer improvements to the currently most efficient algorithm of the domain, ShRec3D, allowing to adjust the reconstruction according to the user needs
Badalato, Nelly. "Structure de déchets lignocellulosiques : effets sur la colonisation, les communautés microbienne et les performances de méthanisation, caractérisés par des approches fonctionnelles et haut-débit". Electronic Thesis or Diss., Paris, AgroParisTech, 2014. http://www.theses.fr/2014AGPT0002.
Pełny tekst źródłaLignocellulosic materials have a high energy potential and are abundant, especially in municipal solid waste and their methanization is a promising waste-to-energy bioprocess. However, owing to their highly complex and heterogeneous structure, they are recalcitrant to anaerobic conditions and the use of pre-treatments is usually required to improve their biodegradation yields. Besides, lignocellulose colonization by cellulolytic microorganisms is a key step for an efficient biodegradation. In this context, the PhD work aimed to better understand the factors affecting waste colonization, to establish the link between lignocellulosic waste colonization and its biodegradation efficiency and to characterize more precisely the mechanisms and interactions within the biomass. A transversal approach was developed, combining cultures of model pure strains and lab-scale methanization microcosms with a complex biomass. Integrated approaches were applied to these studies, combining high-throughput analyses (metagenomics/(meta) proteomics), physico-chemical monitoring of bioconversion and finally physico-chemical characterization of substrates. The main results highlight the important role of lignocellulosic materials chemical and micro-and macro -structural features for their recalcitrance, their biodegradation efficiency and the response of the microbial compartment. The first global quantitative proteomic study on the cellulolytic model Clostridium cellulolyticum was conducted. Results showed an increased biodegradation rate of the facial tissue compared to cotton. This enhanced biodegradation was associated to a particular metabolic profile, a faster and more extensive colonization and finally a quantitative modulation of the cellulasic system. On the other hand, study of lignocellulosic waste methanization confirmed the good agreement between this more realistic system and the above-described model system. It also provided new information about the effects of substrate on microbial community structure. Noticeably, Bacteroidia members predominated in the presence of tissue and a high proportion of Spirochaetes members was observed in the presence of cotton. Finally, study of the effects of wheat straw and cardboard dry grinding revealed the limitations of these pretreatments on biodegradation efficiency. Main key points were a moderate positive effect of wheat straw fine grinding, and the sensitivity of the microbial communities to substrate surface characteristics, as evidenced by the emergence of different microbial communities according to the applied mechanical pretreatment. In conclusion, this work brings new perspectives to the study of lignocellulosic waste recalcitrance by addressing both the structural, functional and ecological aspects. These results contribute to the core fundamental knowledge on bioprocesses. They confirm that the lignocellulosic materials are specific among non-hazardous waste and require the implementation of adapted specific processes
Bruno, Aurélie. "Caractérisation moléculaire des lymphomes primitifs du système nerveux central chez le sujet immunocompétent". Thesis, Université Paris-Saclay (ComUE), 2015. http://www.theses.fr/2015SACLS085.
Pełny tekst źródłaPCNSL represent a rare extranodal diffuse large B cell lymphoma (DLBCL) with a post-GC phenotype whose tumorigenesis is still poorly unknown.Our objective was to characterize the molecular genetic alterations of PCNSL using high throughput technologies.Results: We demonstrated 1/ a high incidence of somatic mutations in genes involved in the BCR/TLR/NF-κB pathway, especially MYD88, CD79B and TBL1XR1; 2/ recurrent chromosome imbalances such as 6q22 loss and 6q (HLA locus) homozygous deletions; 3/ TERT promoter mutations and 4/ gene fusions such as ETV6-IGH. Several alterations are associated with a prognostic impact (6q22 loss and CDKN2A homozygous deletions) or are promising targets for novel therapies.To conclude, PCNSL and extracerebral DLBCL share many similarities in terms of molecular genetic profile despite some specificities. PCNSL may result from a specific tumorigenesis but also from its peculiar microenvironment
Hoang, Cong Tuan. "Prise en compte des fluctuations spatio-temporelles pluies-débits pour une meilleure gestion de la ressource en eau et une meilleure évaluation des risques". Phd thesis, Université Paris-Est, 2011. http://pastel.archives-ouvertes.fr/pastel-00658537.
Pełny tekst źródłaPesson, Marine. "Progression tumorale dans le cancer colorectal : analyse de l'expression de l'ensemble des gènes du génome humain et de l'épissage alternatif par des approches à haut débit". Thesis, Brest, 2013. http://www.theses.fr/2013BRES0087.
Pełny tekst źródłaA genome-wide analysis of mutation, gene expression and alternative pre-mRNA splicing was performed in colorectal normal mucosa, adenoma and adenocarcinoma biopsy samples in order to look for some alterations that could characterize the stepwise “colorectal normal mucosa-adenoma-adenocarcinoma” transition. It was conducted through different microarray-based experiments. Alterations specific for either adenomas or adenocarcinomas were identified. Nevertheless, most deregulated genes in adenocarcinomas were shared between adenomas and adenocarcinomas, in agreement with the notion that adenomas are precursor lesions for adenocarcinomas. Adenomas may have different outcomes, depending on environment, some evolving towards cancer, while others could be prone to disappearance. Pathway enrichment in colorectal lesions and classification of colorectal lesions were investigated. A 40-gene set was identified as a gene expression signature that could help predicting patients, at time of adenoma ablation, with a risk for developing colorectal cancer. Splicing profiles were also identified in colorectal lesions, suggesting that alternative splicing may play a major role in cancer outcome. Finally, a custom microarray was designed with the aim to predict the response of patients before treatment. This custom microarray makes it possible to analyze transcript structure and levels for genes involved in the response to targeted anticancer therapies
Ariel, Olivier. "Analyse de l’expression génique des macrophages bovins face à la maladie de Johne et leur réponse à l’infection in vitro par Mycobacterium avium sous-espèce paratuberculosis". Mémoire, Université de Sherbrooke, 2017. http://hdl.handle.net/11143/11087.
Pełny tekst źródłaNordell-Markovits, Alexei. "Développement d'une librairie de code et d'outils bio-informatiques faciliant l'analyse de grandes quantités de données génomiques". Thèse, Université de Sherbrooke, 2016. http://hdl.handle.net/11143/9601.
Pełny tekst źródłaCarouge, Élisa. "Récepteur MET et fusions ETS : co-acteurs dans la progression du cancer de la prostate". Electronic Thesis or Diss., Université de Lille (2022-....), 2024. https://pepite-depot.univ-lille.fr/ToutIDP/EDBSL/2024/2024ULILS005.pdf.
Pełny tekst źródłaProstate cancer (PCa) has the highest incidence of all male cancers in Europe and the USA. In the advanced stages of the disease, the development of metastases (bone metastases in 80% of cases) leads to a high mortality rate. MET receptor and ETS gene fusions with a hormone-dependent promoter are important actors in the progression of prostate cancer. Among the members of the ETS family of transcription factors, ERG is found in 60% of fusions and ETV1 in 10%. MET is a tyrosine kinase receptor expressed in the advanced stages of the disease, in hormone-resistant tumours and in bone metastases. ERG and ETV1 fusions are found throughout the disease, from initiation to metastatic stages. Interestingly, there are many functional links between MET and ERG/ETV1, suggesting that they belong to the same regulatory pathway. The aim of our study is to understand the individual roles of MET receptor and ETS fusions and their collaboration in PCa progression.To this end, we built hormone-independent CaP cellular models in which MET receptor expression and activity are effective and ERG or ETV1 overexpression has been induced via retroviral infection. These models were used to perform phenotypic tests of proliferation, migration and invasion, comparative transcriptomic analysis (RNAseq) and in vivo tests in humanised mice expressing human HGF. The results we obtained show that the transcription factors ERG and ETV1 induce greater migratory and invasive capacities in vitro and that activation of the receptor signalling pathway amplifies the effects. In vivo, ERG and ETV1 induce larger tumour volumes after subcutaneous injection of the cells, and treatment with a specific MET inhibitor reverses these effects. Finally, a transcriptomic analysis comparing the different models, permits to identify genes differentially expressed according to overexpression of ERG, ETV1 and/or activation of MET pathway, signature target genes potentially involved in tumour progression.The data obtained show, for the first time, a collaboration between MET receptor and ERG/ETV1 factors to induce more aggressive characteristics in PCa models. The project aims to identify the molecular signatures of this cooperation in order to highlight prognostic, diagnostic and targeted therapy tools
Lorentzen, Marc. "Diversity and genomic characteristics of Oenococcus oeni". Thesis, Bordeaux, 2018. http://www.theses.fr/2018BORD0428.
Pełny tekst źródłaOenococcus oeni is a lactic acid bacteria species adapted to the inhospitable environment of fermenting wine, where it shows a remarkable degree of specialization to the stress of low pH and high ethanol that allows it to proliferate where most bacteria fail to survive. The bacteria is supremely important in wine production, because it carries out malolactic fermentation, a process that occurs after alcoholic fermentation, where malic acid is metabolised into lactic acid and the pH of the wine is raised. The species has only a small genome and accumulates mutations several orders of magnitude faster than other lactic acid bacteria due to a loss of DNA mismatch repair genes. This has likely sped up the process of domestication to wine. The degree of specialization has been demonstrated by finding specific populations adapted to red or white wines in the same region. In this study, we used high throughput sequencing and genomics approaches to elucidate the diversity of O. oeni strains, to identify their genomic characteristics and measure their dispersion in different environments as well as their dynamics during fermentation. Because of its importance to wine-making, several hundred strains have been isolated and sequenced. In this work, we have expanded upon the collection of genomes by sequencing strains from cider and kombucha and performing phylogenetic analyses to clarify the population structure of the species. By calculating a species-wide pangenome, we performed comparative genomics to explore gene clusters that were specific to one or more sub-populations. With next generation sequencing, we produced fully circularized genomes from the major sub-populations and analysed their genomic arrangements. These new genomes were annotated with new, automatic pipelines and manual curation for the first time since the publication of the reference genome PSU-1. The evolution of bacterial communities over the course of fermentation, from grape must to finished wine, was examined with 16S amplicon sequencing in four Bordeaux wineries. Using a universal and a specific primer-set, we compared the biodiversity in wines resulting from organic or conventional farming practices. In addition, with the newly defined phylogenetic groups, we developed a qPCR experiment to detail the composition of O. oeni in the fermentations and cemented the dispersal of even rarely isolated strain sub-populations in grape must. This new method was also used to analyse the diversity of O. oeni strains in the base wines of Cognac and during the production of cider, two products that are distinguished from traditional wine production by not using sulfite. The two other species in the Oenococcus genus, kitaharae and alcoholitolerans, are also found in the environments of fermenting beverages. O. kitaharae does not have a functional malolactic gene, but the more recently discovered O. alcoholitolerans was thought capable of performing the malolactic reaction. We characterized this, as well as the species tolerance for the stressors of the wine environment. Finding it unable to survive in wine, we produced a fully circularized genome of O. alcoholitolerans and performed a comparative genomics analysis to identify the O. oeni genes that enable it to tolerate the pH and ethanol, which O. alcoholitolerans and O. kitaharae lacks. In conclusion, we have used the new technologies of next generation sequencing to produce high-quality genomes and performed extensive, species-wide comparative analyses that allowed us to identify patterns in gene presence that provide likely explanations for environmental adaptation
Le, Guennec Kilan. "Variants rares et analyse d'exomes : application à la maladie d'Alzheimer du sujet jeune". Thesis, Normandie, 2017. http://www.theses.fr/2017NORMR148/document.
Pełny tekst źródłaNext-generation sequencing allows studying and analyzing the genetic component part of complexdiseases mediated by rare variants. However, their interpretation represents a major challenge.Indeed, the sequencing of thousands of exomes and genomes revealed the human polymorphismcomplexity and in particular the overrepresentation of rare variants. Despite the development ofsoftwares and variant databases, the prioritization of rare variants remains arduous. My thesis subject was focused on the involvement of rare variants in Alzheimer's disease (AD). From a genetic point of view, AD is caused, in most cases, by a multifactorial determinism, but a minority of cases are autosomal dominant early-onset forms (ADEOAD). The characterization of mutations in the PSEN1, PSEN2 and APP genes as a cause of these Mendelian forms of AD led to the formulationof the amyloid cascade hypothesis, stating that the amyloid-β peptide (Aβ) is triggering the pathophysiological process. In order to detect new genetic risk factors involved in AD, we performed an association study using exome sequencing data from 522 cases with early-onset Alzheimer Disease and 584 controls. The first analyzes focused on single nucleotide variants and short insertions / deletions, and revealed an enrichment in cases of variants that are predicted to be deleterious in the ABCA7 genes. We then then focused on copy number variations (CNVs). The lack of recurrence at the gene-level incited us to work on a gene list. By focusing on the amyloidogenic hypothesis, we built a list of 342 genes involved in the metabolism and toxicity of the Aβ peptide. Thanks to this strategy, we found an enrichment of rare CNVs intersecting this Aβ network in cases.The main result of this CNV study was the identification of a duplication of the 17q21.31 locus in 5patients with a neurodegenerative disease similar to Alzheimer's disease. These patients have aclinical diagnosis of AD, as well as biomarkers and metabolic imaging consistent with an ADneurodegeneration. However, amyloid imaging and neuropathological analysis did not reveal anyamyloid pathology, and were therefore pointing to a pure tauopathy. This CNV study also revealed a partial deletion of the PSEN1 gene, overlapping exons 9 and 10, for which we performed functional studies. We demonstrated that the mutant protein enhanced the production of longer amyloid peptides, the latter being major mediators of Aβ neurotoxicity
Tignat-Perrier, Romie. "Facteurs de structuration des communautés microbiennes de la couche limite atmosphérique". Thesis, Université Grenoble Alpes (ComUE), 2019. http://www.theses.fr/2019GREAU034.
Pełny tekst źródłaUp to 106 microbial cells per cubic meter are found in suspension in the planetary boundary layer, the lowest part of the atmosphere. Direct influences of the planetary boundary layer on humans, crops and diverse ecosystems like soils and oceans make the full understanding of its composition, both chemical and microbiological, of utmost importance. While microbial communities of the planetary boundary layer vary significantly at different temporal and spatial scales, they remain largely unexplored. The main goal of this thesis was to understand how airborne microbial communities are structured in the troposphere with special emphasis on the planetary boundary layer and to identify their main controlling factors. We investigated both the taxonomic and functional composition of airborne microbial communities in the dry phase (i.e. not cloud-associated) over time at nine different geographical sites around the world using high throughput sequencing technologies.Our investigation that focused on microbial taxonomy showed that local landscapes were the main contributors to the global distribution of airborne microbial communities despite the potential occurrence of long-range transport of airborne microorganisms. We also observed that meteorology and the diversity of the surrounding landscapes played major roles in the temporal variation of the microbial community structure in the planetary boundary layer. We further explored the temporal variation of airborne microbial communities at a continental and mountainous site in France (1465 m above sea level) over a full-year. This study demonstrated the importance of the surface conditions (i.e. vegetation, snow cover etc.) of the surrounding landscapes on the taxonomic composition of airborne microorganisms. The seasonal changes in agricultural and vegetated areas, which represented a significant part of the site’s surrounding landscape, were correlated to the shifts in the taxonomic composition of airborne microbial communities during the year. Finally, we investigated the functional composition of microbial communities of the planetary boundary layer to identify whether the physical and chemical conditions of the atmosphere played a role in selection or microbial adaptation of airborne microorganisms. The comparative metagenomic analysis did not show a specific atmospheric signature in the functional potential of airborne microbial communities. To the contrary, their functional composition was mainly correlated to the underlying ecosystems. However, we also showed that fungi were more dominant relatively to bacteria in air as compared to other (planetary bound) ecosystems. This result suggested a selective process for fungi during aerosolization and/or aerial transport and that fungi might likely survive aerosolization and/or aerial transport better than bacteria due to their innate resistance to stressful physical conditions (i.e. UV radiation, desiccation etc.). Our results provide a clearer understanding of the factors (i.e. surrounding landscapes, distant sources, local meteorology, and stressful physical atmospheric conditions) that control the distribution of microbial communities in the atmospheric boundary layer. Our investigations provide a basis for further studies on the prediction and even control of airborne microbial communities that would be of interest for public health and agriculture
Brosseau, Jean-Philippe. "Détection, annotation fonctionnelle et régulation des isoformes de l'épissage alternatif associées au cancer de l'ovaire". Thèse, Université de Sherbrooke, 2012. http://hdl.handle.net/11143/6652.
Pełny tekst źródłaGaudin, Maxime. "Human RNA bait library depletion for human (viral) pathogen discovery using shotgun metagenomic sequencing". Thesis, Aix-Marseille, 2018. http://www.theses.fr/2018AIXM0697/document.
Pełny tekst źródłaViral metagenomics, which is based on the random shotgun sequencing of all viral genomes present in a sample, is a promising approach for blind detection and identification of potential new pathogens. Its use is however still marginal because of the large proportion of human nucleic sequences. In this context, this thesis work aims at improving the metagenomic approach for the clinical diagnosis of viral infectious diseases by increasing the ratio of pathogen-to-host sequences trough depletion of human nucleic acids from the samples. The first chapter of this thesis consists in a bibliographic synthesis of viral metagenomic approaches in clinical research and the challenges we faced in this field. This bibliographic overview also includes a review article on targeted-enrichment sequencing approaches for pathogen detection in the field of human infectious diseases. The second chapter proposes a methodological development allowing the enrichment of non-human sequences from metagenomes through hybridization and capture of human nucleic acids with biotinylated human RNA probes. The third chapter is divided into two sub-chapters that propose the application of this protocol to the detection of putative pathogens in (1) a fatal case of encephalitis and (2) an enigmatic case of blood-culture negative infectious endocarditis. The methodological approach developed during this work is finally discussed in a fourth chapter, which also replaces the results obtained in the broader context of emerging infectious diseases and validation of the causal link between the agent detected and the observed pathology