Affichage des résultats 481 à 500 sur 1349 au total
Basal-like breast cancers are among the breast cancers with the poorest prognoses and patients do not benefit from any targeted therapy yet. We aim to identify the deregulated signaling pathways using genomic, transcriptomic and proteomic (RPPA) data in order to identify therapeutic targets. In this talk, I will focus on the analysis of SNP and CGH data. More specifically, I will discuss several statistical and algorithmic challenges directly related to their statistical analysis.1) Normalisation One important issue when analyzing SNP profiles is their normalisation. Indeed, especially with tumour profiles, it cannot be assumed that most of the genome is normal and it has been shown that not taking these genomic alterations into account while normalising leads to over-correction. We propose a method to estimate the signal (or copy number) and correct technical artefacts simultaneously.2) Exact and Fast segmentation A CGH profile can be viewed as a succession of segments representing regions in the genome that share the same DNA copy number. Multiple-change-point detection methods constitute a natural framework for their analysis and the detection of breakpoints. However, recovering the optimal position of the breakpoints is not an easy task, especially for large SNP profiles such as Affymetrix SNP 6.0. We propose an algorithm to recover quickly the best segmentation (the maximum likelihood estimate).3) Assessing the quality of a segmentation Assessing the quality of a segmentation and in particular the confidence we have in a particular breakpoint is a difficult problem. We propose algorithms and statistical methods to assess and take into account the quality of possible segmentations.
This communication will have two distinct aims. Firstly, it is intent to introduce my work in the area of philosophy of science to the members of the Laboratory I joined last November. I will briefly present my two main research themes, namely 1° the difficulty to define a scientific object such as animal behavior, and 2° scientific reasoning in biology, as they have been introduced in the PhD thesis I defended last year (Epistémologie historique de l'étude du comportement animal). Secondly, this communication also aims to convince the audience about the relevance and the potential utility of philosophy of science for the practice of science.
Transposable elements (TEs) are often thought to be harmful because of their potential to spread heterochromatin (a repressive chromatin state) into nearby sequences. However, there are few examples of spreading of heterochromatin caused by TE insertions, even though TEs are often found in regions of repressive chromatin. We developed a model to study heterochromatin induction by TEs in a natural system. We studied two mouse embryonic stem cell lines harboring polymorphic retrotransposons belonging to three different families, such that one cell line possesses a particular TE copy (full site) while the other cell line lacks the copy at the same genomic location (empty site). We compared the chromatin state of these full and empty sites. Nearly all IAP copies, a family of retroviral-like elements, are able to strongly induce repressive heterochromatin surrounding their insertion sites, with the repressive histone modifications extending at least one kb and sometimes up to 5 kb from the IAP. This heterochromatin induction was not observed for the LINE family of non-viral retrotransposons and for only a minority of copies of another retroviral-like family, ETn/MusD. We found only one gene that was partly silenced by IAP-induced heterochromatin. Therefore, while induction of heterochromatin occurs after IAP insertion, measurable impacts on host gene expression are rare. Nonetheless, this phenomenon may play a role in rapid change in gene expression and therefore in host adaptive potential. Post Doc, Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada
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Selon l'hypothèse du syndrome de « train de vie » (STV; Ricklefs & Wikelski 2002; Wikelski et al. 2003), des espèces ou populations vivant dans des conditions environnementales différentes montreraient des différences dans leurs caractéristiques physiologiques (métaboliques, hormonales, immunitaires) ayant co-évolué avec certaines particularités biodémographiques propres à chacune de ces conditions. De manière surprenante, deux facettes potentielles du STV ont été négligées à ce jour: 1) en dépit d'un nombre croissant d'études sur les liens entre comportement, métabolisme et traits d'histoire de vie, les différences comportementales ont rarement été considérées dans ces syndromes; 2) Les STV pourraient facilement être appliqués à l'étude intra-populationnelle des (co)variations entre traits. Dans cette présentation, je montre qu'il est possible d'intégrer les traits de personnalité à l'étude du STV. A l'aide d'exemples d'études sur différents modèles animaux, j'illustrerai comment cette approche heuristique permet l'étude du maintien de la variabilité des traits de personnalité dans des populations naturelles.
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abstract: This talk introduces some of the ideas behind cophylogenetic analysis, which aims to recover ancient coevolutionary events between ecologically linked taxonomic units such as hosts and parasites, hosts & symbionts, species and genes. It describes some of the current challenges in this area, in terms of theoretical results, implementation, and some real examples.bio: M Charleston is an Associate Professor at the University of Sydney in Australia. He did his PhD at Massey University, and has worked at U.T. Austin, University of Glasgow, and University of Oxford. His research is mainly in evolutionary biology and bioinformatics.
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The net reproductive rate, R_0, measures the expected lifetime reproductive output of an individual, and plays an important role in demography, ecology, evolution, and epidemiology. Well-established methods exist to calculate it from age- or stage-classified demographic data. Because it is an expected value, however, R_0 provides no information on variability. Many empirical measurements of lifetime reproduction have revealed high levels of variability, and often positive skewness. This is often interpreted as evidence of heterogeneity, and thus of an opportunity for natural selection. However, variability provides evidence of heterogeneity only if it exceeds the level of variability that would be expected in a cohort of identical individuals all experiencing the same vital rates. Such comparisons require a way to calculate the statistics (variance, coefficient of variation, skewness) of lifetime reproduction from demographic data. These calculations have not been possible; here, I present a new approach, using the theory of Markov chains with rewards, that gives all the moments of the distribution of lifetime reproduction. The approach applies to age- or stage-classified models, to constant, periodic, or stochastic environments, and to any kind of reproductive schedule. As examples, I analyze data from several empirical studies of a variety of animal and plant taxa.For more details, please go to http://cgphimc.univ-lyon1.fr/CGphiMC/Semovi/13avril2011.php
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Le risque attribuable est une mesure qui permet de quantifier l'impact d'une exposition en terme de nouveaux cas d'une pathologie dans un population. Pouvant être interprété comme la proportion de cas attribuables ou associés à cette exposition, il prend en compte à la fois la prévalence de l'exposition dans la population et la force d'association entre l'exposition et la maladie. Le risque attribuable est parfois estimé à partir d'études de cohorte prospectives dans lesquelles on observe la survenue ou non au cours du suivi d'un événement tel que le diagnostic d'une maladie. Les données correspondantes sont des données censurées de type délai de survenue plus communément appelées « données de survie ». Des publications très récentes ont examiné l'adaptation du concept de risque attribuable à ces données. Différentes définitions ont été proposées ainsi que des méthodes d'estimation paramétriques, semi- ou non-paramétriques. Cet exposé présente une revue de ces développements récents en considérant la pertinence des définitions proposées, leurs potentielles difficultés d'interprétation et les avantages et limites des méthodes d'estimation
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