1,721,013 research outputs found
Analysis at high resolution of 3D chromosomal folding of eucaryotic genome
No full textL’information génétique est portée par la molécule d’ADN, un polymère de nucléotides de très grande taille. Afin de mieux comprendre les mécanismes impactant le repliement de l’ADN, on peut exploiter une technique de génomique qui permet de quantifier les contacts entre régions distales du génome. Cette technique expérimentale appelée ’capture de conformation de chromosome’ (Hi-C) donne des informations quantitatives sur l’architecture et le repliement tridimensionnel des chromosomes dans le noyau. Largement utilisée chez l’Homme, la souris et la drosophile, cette technique a grandement évolué durant ces dernières années, produisant ainsi des données de qualité variable. Jusque-là étudiées à des résolutions assez grossières, notre objectif est d’étudier les données Hi-C déjà publiées à des résolutions plus fines. Pour cela, j’ai développé un outil bioinformatique, Boost-HiC, pour améliorer l’analyse des contacts chromosomiques. Fort de cette expertise, je proposerai alors une analyse comparative des structures spatiales des génomes eucaryotes, permettant de clarifier comment extraire les compartiments génomiques de manière optimale. Cette expertise sera utilisée également pour décrire le lien entre les bordures des domaines topologiques de la chromatine et la position dans le génome humain des mutations ponctuelles prédisposant au cancer.Genetic information is encoded in DNA, a huge-size nucleotidic polymer. In order to understand DNA folding mechanisms, an experimental technique is today available that quantifies distal genomic contacts. This high-throughput chromosome conformation capture technique, called Hi-C, reveals 3D chromosome folding in the nucleus. In the recent years, the Hi-C experimental protocol received many improvements through numerous studies for Human, mouse and drosophila genomes. Because most of these studies are performed at poor resolution, I propose bioinformatic methods to analyze these datasets at fine resolution. In order to do this, I present Boost-HiC, a tool that enhanced long-range contacts in Hi-C data. I will then used our extended knowledge to compare 3D folding in different species. This result provides the basis to determine the best method for obtaining genomic compartements from a chromosomal contact map. Finally, I present some other applications of our methodology to study the link between the borders of topologically associating domains and the genomic location of single-nucleotide mutations associated to cancer
Yeast synthetic genomics with deep learning
No full textDes avancées technologiques récentes dans le domaine des biotechnologies telles que CRISPR et la synthèse de novo d'oligonucléotides d'ADN permettent désormais de modifier précisément et dans de grandes proportions les génomes. Des projets visant à concevoir des génomes partiellement ou complètement synthétiques, en particulier des génomes de levure, se sont développés en tirant profit de ces technologies. Cependant, pour atteindre ces objectifs, il est nécessaire de contrôler l'activité des séquences artificielles, ce qui demeure aujourd'hui un défi. Heureusement, l'émergence récente de méthodologies d'apprentissage profond capables de reconnaître la fonction génomique associée à une séquence d'ADN peut fournir un outil puissant pour anticiper l'activité des génomes synthétiques et en faciliter la conception. Dans cette perspective, nous proposons d'utiliser les méthodologies d'apprentissage profond afin de concevoir des séquences synthétiques de levure permettant de contrôler la structure locale du génome. Je présenterai en particulier la méthodologie que nous avons développée afin de concevoir des séquences synthétiques positionnant précisément les nucléosomes - une molécule déterminant la structure de l'ADN à la plus basse échelle - chez la levure. Je montrerai aussi que cette méthodologie ouvre la perspective de concevoir des séquences contrôlant le niveau de structure immédiatement supérieur : les boucles. La conception de séquences contrôlant la structure locale permet d'identifier précisément les déterminants de cette structure.Recent technological advances in the field of biotechnologies such as CRISPR and the de novo DNA oligonucleotides synthesis now make it possible to modify precisely and intensively genomes. Projects aiming to design partially or completely synthetic genomes, in particular yeast genomes, have been developed by taking advantage of these technologies. However, to achieve this goal it is necessary to control the activity of artificial sequences, which remains a challenge today. Fortunately, the recent emergence of deep learning methodologies able to recognize the genomic function associated to a DNA sequence seems to provide a powerful tool for anticipating the activity of synthetic genomes and facilitating their design. In this perspective, we propose to use deep learning methodologies in order to design synthetic yeast sequences controlling the local structure of the genome. In particular, I will present the methodology we have developed in order to design synthetic sequences precisely positioning nucleosomes - a molecule determining the structure of DNA at the lowest scale - in yeast. I will also show that this methodology opens up the prospect of designing sequences controlling the immediately higher level of structure: loops. The design of sequences controlling the local structure makes it possible to precisely identify the determinants of this structure
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
An asymmetric Ising model for spatial gene regulation
No full textLa régulation génétique joue un rôle majeur dans le développement embryonnaire. La structure d’un organisme est prédéfinie par des motifs spatio-temporels d’expression de gènes précurseurs. Les processus de régulation impliquant plusieurs gènes sont souvent représentés comme des réseaux de régulation génétique (RRG). Dans cette thèse, je présente un nouveau modèle de RRG avec une composante spatiale. Ce modèle est une variante du modèle d’Ising, désigné pour avoir un nombre minimal de paramètres. Ces paramètres, les interactions entre gènes et leur portée, ont des rôles similaires aux paramètres d’un automate cellulaire de réaction-diffusion. Ce modèle est capable de former des motifs complexes, tel que des motifs de Turing, ce qui n’avait jamais été observé dans des modèles de type Ising avec interactions à courte portée, et le paramètre d’ordre associé ne dépend pas de la taille du système. Ce modèle est appliqué à la segmentation dans le développement précoce de la Drosophile, en particulier à la régulation du gène eve. Une méthode d’échantillonnage issue de la physique statistique est employée, l’algorithme Wang-Landau. Il permet d’identifier les sous-volumes de l’espace des phases qui sont solution pour produire un motif donné. La comparaison de résultats obtenus sur des données en 1D ou en 3D montre que les espaces des solutions s’intersectent mais ne sont pas confondus. Enfin, cette thèse questionne cette vision sous forme de réseau et redéfinit un code régulation génétique dont l'adapteur serait le gène domain, une séquence encadrant le locus du gène dans le génome.Gene regulation is a major actor of embryonic development. The structure of an organism is predefined by spatio-temporal patterns of expression from precursors genes. Regulation processes involving multiple genes are often represented by Gene Regulation Networks (GRN). In this thesis I present a novel spatial model of GRN. This model is a variant of the Ising model and is designed to have a minimal number of parameters. Its parameters, inter-actions between genes and the corresponding range of interaction, have similar roles to those of a reaction-diffusion automata. This model is able to form complex patterns, such as Turing patterns, which has never been osbserved before in short-range Ising-like models. This model is applied to early stage segmentation of Drosophila, in particular to the regulation of the gene eve. A sampling method, the Wang-Landau algorithm, is applied to the model. It is used to identify, within the parameter space, sub-volumes of networks producing a given pattern. The comparison of results obtained from 1D or 3D data show the solutions spaces intersect but are not identical. Finally, this thesis question the view of gene regulation in terms of networks, and redefined a gene regulation code whose adaptor would be the gene domain, a sequence surrounding the gene locus along the genome
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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