Recherche avancée
Affichage des résultats 161 à 180 sur 8427 au total
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Conservation of Alliance of Zero Extinction species: an important role to play by zoos
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Utilisation des modèles à variables latentesndans l'analyse de données de neuro-imagerie
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Spatio-temporal mapping of pathogen epidemics
Infectious diseases account for one fourth of human deaths worldwide. With pathogen collections of ever-increasing sizes, it becomes possible in theory to reconstruct past epidemic events on continental or worldwide scales and to gain actionable insights into the driving forces of pathogen dispersal and evolution. Current population genetics methods excel at this task, however their computational cost hampers their application on massive (n > 1,000) genomic datasets. Here we introduce a novel approach, ancestral state interpolation (AncSI), to reconstruct epidemics through space and time in a computationally efficient fashion. AncSI infers past information (including location, resistance or transmission success) relative to all isolates in the study population in a given time period. By computing series of fine-grained time period, AncSI allows for the visualization of epidemic dispersal in the form of video files. We reconstruct the epidemic progression across Eurasia and Africa of two deadly bacterial pathogens, namely the Mycobacterium tuberculosis Beijing family (n = 4,000 isolates with an evolution on the millenial scale) and the Salmonella Typhi H58 clone (n = 2,000 isolates with an evolution on the decade scale). In both cases, AncSI-inferred epidemic dynamics exhibited a near-perfect match with the conclusions of previous studies based on hypothesis-driven population genetics analyses. Furthermore, AncSI results highlighted previously unreported features of the epidemics such as a Korean (rather than Chinese) emergence of M.tuberculosis Beijing. Our results indicate that an accurate reconstruction of past epidemics can be obtained efficiently from genomic datasets, potentially leading to novel discoveries by leveraging the fast growing collections of pathogen genomes.
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The R Epidemics Consortium: building the next generation ofnstatistical tools for outbreak response using R
The recent West African Ebola outbreak has been a terrible reminder for the need to gain timely situation awareness, in order to inform and guide public health intervention and maximise the chances of mitigating disease outbreaks. Unfortunately, many tools are still lacking for addressing the challenges, both statistical and technical, posed by the analysis of outbreak data. This presentation will introduce the R Epidemics Consortium (RECON), an initiative bringing together public health officers, statisticians, modellers and software developers to develop a new generation of tools for outbreak response using the R software. We will argue that R is a platform of choice for the development of cutting-edge methodology which can further our understanding of disease dynamics. This point will be illustrated using outbreaker2, a new R package for reconstructing disease outbreaks using various kinds of epidemiological and genetic data. We will also show how R can be used for addressing some of the more technical challenges inherent to the outbreak response context, taking the packages incidence and epicontacts as examples. We will conclude by reflecting on how the typical life-cycle of methodological development is altered during emergency outbreak response, and on what novel practices may be considered to address some of these issues.http://repidemicsconsortium.org/ Keywords: methods, R, statistics, software, RECON, tools
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Aux frontières des performances physiologiques
Le vieillissement est un phénomène complexe intervenant à toutes les échelles de l'organisation biologique, du niveau moléculaire jusqu'au niveau des performances de l'organisme. La locomotion est une fonction neurophysiologique hautement intégrée illustrant un tel processus multi-échelle. Le déclin des performances de locomotion avec l'âge, comme la vitesse maximale, a été observé pour de nombreuses espèces, aussi bien en captivité qu'en milieu naturel. Cependant, ces descriptions restent souvent succinctes, sans précision sur la progression de ces performances au cours du vieillissement. Dans ces travaux, nous utilisons une équation bi-phasique pour décrire la relation entre performance de locomotion et âge sur l'ensemble de la durée de la vie pour Caenorhabditis elegans, Mus domesticus, Canis familiaris, Equus caballus et Homo sapiens. Les performances maximales de locomotion se révèlent être des bio-marqueurs robustes pour suivre la progression des performances sur l'ensemble de la durée de vie des animaux, permettant ainsi d'estimer le pic physiologique et le début du déclin des performances. De plus, dans tous les cas, nous remarquons que la forme de progression des performances maximales selon l'âge est similaire et conservée d'une espèce à l'autre ; seule varie la pente dans le temps, dépendant de l'espèce et la performance mesurée. Nous avons ensuite étudié le développement et l'expansion de cette dynamique au cours du siècle dernier pour les performances athlétiques maximales d'Homo sapiens. Cette étude révèle que la forme s'est progressivement précisée au cours du temps en s'étendant à tous les âges et suivant homothétiquement la progression des records du monde. Néanmoins, la progression semble ralentir au cours des dernières décennies, laissant présager l'atteinte possible des limites biologiques d'Homo sapiens. Ces travaux offrent de nouvelles perspectives sur l'utilité des approches comparatives et l'utilisation d'un bio-marqueur comme les performances de locomotion pour suivre les dynamiques sur l'ensemble de la durée de vie à différentes échelles. Elles apportent aussi un regard novateur sur la progression des performances avec l'âge, en intégrant à la fois les processus de développement et de vieillissement, permettant ainsi de préciser les pics physiologiques et la forme des progressions des performances sur toute la durée de la vie. Institut de Recherche bio-Médicale et d'Epidémiologie du Sport (IRMES), EA 7329, Institut National du Sport, de l'Expertise et de la Performance (INSEP) and Université Paris Descartes, Sorbonne Paris Cité, Paris, France / (2) Laboratoire Matière et Systèmes Complexes, UMR 7057, Université Paris Diderot and CNRS, Sorbonne Paris Cité, Paris, France.
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Functional prediction at the (meta)-genomic scale by evolutionary analysis.
Functional prediction is a cornerstone in molecular biology. In this seminar, I will talk about current phylogenomic approaches to functional annotation and gene family characterization. In particular, I will focus on the use of fine-grained orthology detection for functionally annotating novel genomes, phylostratigraphic methods to date the emergence of particular gene functions, and current challenges in the discovery of novel gene functions out massive metagenomic datasets.
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Are social scents partly produced by the microbiota?
Animal bodies house trillions of bacteria, which can influence host behavior in ways that have far-reaching implications for host ecology and evolution. Recent studies have revealed surprising roles for bacteria in shaping behavior across many animal taxa. But questions remain and recent perspective papers have emphasized the need of studying the interactions between microbiota and host behavior. Although it has long been posited that microbiota can influence host behaviour by affecting chemical cues that animals use to communicate, this purported relationship has only recently received renewed attention owing to the advent of new sequencing technologies. My work takes place into this framework, and I will present various results that link microbiota and odor cues in birds and mammals.Odeurs et microbiote chez les vertébrésDepuis quelques années, le rôle des bactéries dans l'écologie et l'évolution des animaux suscite un grand intérêt théorique. Néanmoins, bien que les bactéries semblent jouer un rôle fondamental dans la valeur adaptative des individus, la communauté scientifique vient tout juste de découvrir l'ampleur de leur diversité et fonctions. En particulier, il a été suggéré que le microbiote pouvait être, en partie, responsable de la production des odeurs corporelles utilisées par les animaux pour communiquer avec leurs conspécifiques. Etant donné l'importance de la communication chimique à travers le règne animal, l'altération des odeurs par le microbiote pourrait être une force qui façonne de nombreux comportements. Cependant, malgré l'intérêt que ce sujet suscite, très peu d'études se sont, jusqu'à présent, penchées sur cette question. Mes travaux de recherches se placent dans ce contexte théorique, et je présenterai différents résultats sur les signaux odeurs et le lien avec le microbiote chez les oiseaux et les mammifères.
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Causes and consequences of recombination rate variation in avian genomes
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Understanding regulatory networks in the era of massively parallel sequencing: did we lose our genetic switches and feedback loops?
The turn from the 20th to the 21st Century was marked by a drastic change in the scale at which biologists study regulatory networks. In the 1990, a PhD student could spend years analysing the regulation of one particular gene by one or a few transcription factors. Microarray technologies enabled monitoring the expression of all the genes of an organism in a single experiment (transcriptome arrays), and to lead genome-wide location analysis to report supposedly exhaustive lists of transcription factor binding sites. Next Generation Sequencing amplified the movement, and many labs are now combining ChIP-seq and RNA-seq experiments to get a wide view on transcription factor binding locations, histone modifications, and transcriptional responses to a multitude of conditions, cell types, developmental stages, etc. In the first part of the talk, I will present some of the bioinformatics approaches and tools that we developed to analyse regulatory motifs from various types of high-throughput data (e.g. co-expression clusters, ChIP-seq peaks, replication origins).At the light of the evolution of the domain, I would also like to address a more general question about the insights gained from high-throughput approaches on fundamental mechanisms of regulation. Indeed, it implicitly became standard to consider that a typical high-throughput experiments should return thousands of significant features (differentially expressed genes, TF binding sites, active enhancers). This however does not fit with our classical models, were transcription factors would turn on or off specific sets of target genes ("regulatory switches"), thereby forming regulatory networks whose behaviour was understandably determined by feedback loops. How can we conciliate the undeniable robustness of regulatory networks with the apparent noisiness of binding and transcription profiles?
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Reconstitutions du climat, des régimes alimentaires et de la thermophysiologie à partir des compositions isotopiques des fossiles
L'évolution du vivant peut être déduite du registre fossile qui en est de facto le référentiel temporel. Les compositions en isotopes stables de leurs restes biominéralisés permettent de quantifier aussi bien des paramètres extrinsèques comme le complexe climat-environnement qu'intrinsèques comme la place d'un organisme vivant dans une chaîne trophique ou encore sa thermophysiologie. Au cours de ce séminaire quelques exemples seront abordés tels que 1) le régime alimentaire de certains oiseaux fossiles qui ont vécu au Tertiaire, 2) le statut thermophysiologique des reptiles marins géants du Mésozoïque et 3) l'évolution de la température des océans au cours de la plus grande phase de biodiversification marine du Paléozoïque.
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Single-Cell-Based Analysis Highlights a Surge in Cell-to-Cell Molecular Variability Preceding Irreversible Commitment in a Differentiation Process
In some recent studies, a view emerged that stochastic dynamics governing the switching of cells from one differentiation state to another could be characterized by a peak in gene expression variability at the point of fate commitment. We have tested this hypothesis at the single-cell level by analyzing primary chicken erythroid progenitors through their differentiation process and measuring the expression of selected genes at six sequential time-points after induction of differentiation. In contrast to population-based expression data, single-cell gene expression data revealed a high cell-to-cell variability, which was masked by averaging. We were able to show that the correlation network was a very dynamical entity and that a subgroup of genes tend to follow the predictions from the dynamical network biomarker (DNB) theory. In addition, we also identified a small group of functionally related genes encoding proteins involved in sterol synthesis that could act as the initial drivers of the differentiation. In order to assess quantitatively the cell-to-cell variability in gene expression and its evolution in time, we used Shannon entropy as a measure of the heterogeneity. Entropy values showed a significant increase in the first 8 h of the differentiation process, reaching a peak between 8 and 24 h, before decreasing to significantly lower values. Moreover, we observed that the previous point of maximum entropy precedes two paramount key points: an irreversible commitment to differentiation between 24 and 48 h followed by a significant increase in cell size variability at 48 h. In conclusion, when analyzed at the single cell level, the differentiation process looks very different from its classical population average view. New observables (like entropy) can be computed, the behavior of which is fully compatible with the idea that differentiation is not a "simple" program that all cells execute identically but results from the dynamical behavior of the underlying molecular network.http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1002585
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Équipe Biodémographie Évolutive et Équipe Baobab
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Experimental evolution of ageing
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deux équipes:
-Modélisation et Écotoxicologie Prédictives - Génétique et Évolution des Interactions Hôtes-Parasites
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Title to be announced
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Testing the invasive pathogen hypothesis of rapidly declining bumble bee populations in North America
Bumble bees are one of our most important wild pollinators, and populations are declining globally. Causes of decline appear to vary geographically. In Europe, for example, the proposed drivers are climate change, loss of floral resources and pesticides. In North America, however, a widely accepted hypothesis suggested that contact with an exotic European strain of fungal pathogen, Nosema bombi, was the sole cause of a precipitous decline. We have tested this exotic pathogen hypothesis using multiple genetic and genomic tools.
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Équipes Ecoépidémiologie Evolutionniste & Epigénétique et Formation du Zygote
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Génomique de la domestication des plantes
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Deux équipes du LBBE présentent leurs travaux:
- Évaluation et Modélisation des Effets Thérapeutiques - Bioinformatique, Phylogénie et Génomique Évolutive
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Comment évaluer la médecine personnalisée en cancérologie : Des études rétrospectives aux essais randomisés
Personalized medicine is defined by the National Cancer Institute as "a form of medicine that uses information about a person's genes, proteins, and environment to prevent, diagnose, and treat disease." In oncology, the term "personalized medicine" arose with the emergence of molecularly targeted agents. The prescription of approved molecularly targeted agents to cancer patients currently relies on the primary tumor location and histological subtype. Predictive biomarkers of efficacy of these modern agents have been exclusively validated in specific tumor types. A major concern today is to determine whether the prescription of molecularly targeted therapies based on tumor molecular abnormalities, independently of primary tumor location and histology, would improve the outcome of cancer patients. This new paradigm requires prospective validation before being implemented in clinical practice. In this communication, we will first review different designs, including observational cohorts, as well as nonrandomized and randomized clinical trials, that have been recently implemented to evaluate the relevance of this approach. We then focus on the SHIVA trial, a randomized proof-of-concept phase II trial comparing therapy based on tumL'inscription est gratuite mais obligatoire et doit se faire au plus tard le jeudi 28 septembre 2017 par courriel à stephanie.robert@chu-lyon.frecular profiling versus conventional therapy in patients with refractory cancer. We will present various aspects of implementation, underlying statistical and design questions, limits and strengths and review the results using this prism.