Symbiose seminars

  • Modélisation de la dynamique des réseaux de signalisation SBGN-AF à l'aide de programmes logiques normaux.

    Adrien Rougny (LRI)
    Thursday, October 16, 2014 - 10:30
    Room Minquiers
    Talk abstract: 

    Un grand nombre de réseaux de signalisation sont disponibles dans la littérature ou dans des bases de données sous forme de graphes d'intéractions. Afin de comprendre les systèmes sous-jacents à ces réseaux et de pouvoir les modifier dans un but principalement médical, il est nécessaire de comprendre leur comportement dynamique. C'est pourquoi un grand nombre de techniques de modélisation de la dynamique de ces réseaux moléculaires ont été développées. Il est notamment possible de modéliser la dynamique de ces systèmes par des réseaux booléens. La construction de ces réseaux booléens à partir de graphes d'intéractions nécessite une paramétrisation des fonctions booléennes, le plus souvent réalisée à partir de l'interprétation de résultats expérimentaux. Nous exposerons dans cette présentation une méthode de paramétrisation réalisée sans données expérimentales mais à partir de principes biologiques généraux régissant la dynamique des réseaux de signalisation. Dans notre méthode, les réseaux booléens sont exprimés sous forme de programmes logiques normaux, à partir desquels leurs états stationnaires et trajectoires sont calculés.

  • Modeling dynamics of cell-to-cell variability in TRAIL-induced apoptosis explains fractional killing and predicts reversible resistance

    Gregory Batt (INRIA, Rocquencourt)
    Thursday, October 9, 2014 - 10:30
    Room Minquiers
    Talk abstract: 

    TRAIL induces apoptosis selectively in cancer cells and is currently tested in clinics. Having a mechanistic understanding of TRAIL resistance could help to limit its apparition. Several observations suggested that protein level fluctuations play an important role in TRAIL resistance and its acquisition. However, quantitative, systems-level approaches to investigate their role in cellular decision-making processes are lacking. We propose a generic and principled approach to extend signal transduction models with protein fluctuation models for all proteins in the pathway. The key aspect is to use standard protein fluctuation models for long-lived proteins. We show that its application to TRAIL-induced apoptosis provide a quantitative, mechanistic explanation to previously published but yet unexplained critical observations.

  • Annoyances in metagenomic data analysis and interpretation

    Thomas Bruls (Genoscope)
    Thursday, September 25, 2014 - 10:30
    Room Minquiers
    Talk abstract: 
    Sustained developments in sequencing technology have fueled a range of
    new applications in various fields of life sciences, among which
    metagenomics (aka community genomics or environmental genomics), whose
    promise is to deliver deeper insights into the so-called "unseen majority".
    
    Beyond issues common to other data intensive applications, metagenomics 
    faces difficulties arising from the "in situ" structure of microbial 
    communities, which hinder the possibility of generating accurate 
    assemblies from even moderately complex metagenomes.
    
    These limitations have prompted or renewed interest in assembly-free
    methods for sequence analysis, which are nowadays intensively studied
    from both statistical and algorithmic point of views.
    
    In this talk, we will discuss and illustrate through various real
    world examples (and some less real ones) how such methods, including
    so-called "binning" methods, can help to increase biological
    interpretability of metagenome datasets.
    
    We will also sketch the layout of a software development project that
    aims at scalable variable selection for biomarker discovery from large
    and complex metagenomic datasets. It involves a nested clustering
    procedure combining two types of features extracted from the
    sequences: a coverage related signal (captured using long k-mers), and
    a composition related one (captured using shorter k-mers).
    
    If we have time left, we will evoke an intriguing spectral algorithm
    that has roots in the pre-genomic era, e.g. was succesfully applied in
    the context of physical mapping efforts, and that could be amenable to
    solve some sequence assembly problems.
  • Swarm: robust and fast clustering method for amplicon-based studies

    Frédéric Mahé (Department of Ecology Technische Universität Kaiserslautern )
    Thursday, September 4, 2014 - 10:30
    Room Minquiers
    Talk abstract: 

    Popular de novo amplicon clustering methods suffer from two fundamental flaws: arbitrary global clustering thresholds, and input-order dependency induced by centroid selection. Swarm was developed to address these issues by first clustering nearly identical amplicons iteratively using a local threshold, and then by using clusters' internal structure and amplicon abundances to refine its results. This fast, scalable, and input-order independent approach reduces the influence of clustering parameters and produces robust operational taxonomic units, improving the amount of meaningful biological information that can be extracted from amplicon-based studies.

  • Arthropod Genome Sequencing at the Baylor College of Medicine Human Genome Sequencing Center.

    Stephen Richards (Baylor College of Medicine Human Genome Sequencing Center.)
    Thursday, June 26, 2014 - 10:30
    Room Aurigny
    Talk abstract: 

    We have long been pioneered the sequencing of insects genomes, from Drosophila melanogaster to Aphids, Beetles and Centipedes.As decreasing sequencing costs have allowed, we are expanding our investigations to the phylum of Arthropods. As a pilot for the insect 5,000genomes project, we are sequencing a pilot of 30 arthropod genomes, to identify practical issues and solutions for the selection, DNA isolation, sequencing, assembly, annotation, analysis and publication of multiple arthropod genomes.Here we describe examples demonstrating the power of the de-novo genome to drive biology, and the successes, problems and lessons learned so far from our pilot project. We also present the automated annotation pipeline used for the project. We hope that this project will inform larger projects in the future.  

  • Deciphering respective genome wide roles of bacteria within a community responsible for copper bioleaching metabolic processes: an integrative systems ecology approach

    Philippe Bordon (Univ. of Chile)
    Thursday, May 22, 2014 - 10:30
    Room Aurigny
    Talk abstract: 
    Bioleaching process consists in the extraction of metals from ores
    through the cooperative participation of several extremophile
    microorganisms. Due to its great industrial interest, different studies
    have extensively focused on identifying isolated contributions of single
    strains to the process. Even though these studies achieved important
    advances, the functioning of a bioleaching consortium as a whole remains
    far from being understood. From a holistic perspective, this
    presentation proposes a novel integrative systems ecology approach that
    aims to give a functional sense to a metagenomic consortium through the
    integration of genomic and metabolic knowledge at genome scale. Using
    public genome data of five bacterial strains involved in copper
    bioleaching: Acidiphilium cryptum, Acidithiobacillus ferrooxidans,
    Acidithiobacillus thiooxidans, Leptospirillum ferriphilum and
    Sulfobacillus thermosulfidooxidans, we first reconstructed a global
    integrative metabolic network. Next, using a parsimony assumption, we
    decipher a set of genes, called SGS, that take an active part in
    metabolic pathways related to bioleaching and are consecutive on their
    respective genomes, adding the constraint that the associated metabolic
    reactions are also closely connected within metabolic networks. Finally,
    SGS analysis showed that no segment is shared by five bacteria,
    suggesting that no single organism allows alone the copper bioleaching,
    but also pinpoints to the combination of bacterial interactions
    necessary for promoting these pathways, as well as the major hub role of
     A. cryptum. Overall, the SGS paradigm depicts genomic functional units
    and their respective role to maintain metabolic pathways, information
    that is crucial to genetically monitor bacterial participation as a
    whole in environmental processes
    
  • Enhancing reuse in scientific workflows

    Sarah Cohen-Boulakia (LRI, Université Paris-Sud)
    Thursday, May 15, 2014 - 10:45
    Room Aurigny
    Talk abstract: 

    Scientific workflows have been introduced to enhance reproducibility, share and reuse of in-silico experiments. Their simple programming model appeals to bioinformaticians, who can use them to specify complex data processing pipelines.

    In this talk, I will first present the results of a study we performed on workflow (re)use based on a large set of public scientific workflows: While the number of available scientific workflows is increasing along with their popularity, workflows are not (re)used and shared as much as they could be.

    I will then present several projects which aim at enhancing workflow reuse while focusing more specifically on the recent DistillFlow project. DistillFlow proposes to reduce the structural complexity of workflows to make workflows easier to understand for users. The refactoring approach followed in DistillFlow has provided very interesting results both in the 1,500 public workflows from myexperiment.org and on the more curated workflow sets from the BioVel project (workflows to analyze biodiversity data).

  • Inférence des voies métaboliques chez les espèces non-modèles: de la génomique à la métabolomique

    Gabriel Markov (Tuebingen)
    Tuesday, April 15, 2014 - 10:30
    Room Aurigny
    Talk abstract: 

    Actuellement, pour savoir si une voie métabolique connue est présente chez une espèce non-modèle, les bioinformaticiens se concentrent sur la recherche d'enzymes orthologues dans l'espèce modèle la plus proche. Souvent, la présence de quelques enzymes orthologues est considérée comme une preuve suffisante de la conservation de la voie métabolique d'intérêt, mais ce raccourci n'est pas toujours justifié. Quelles sont les informations que fournit la génomique comparative sur la conservation des voies métaboliques, et en quoi la métabolomique s'avère-t-elle un complément indispensable pour l'étude à haut débit de la diversité métabolique chez les espèces non-modèles? 

  • La prédiction du noyau du repliement des protéines globulaires

    Jacques Chomilier (BiBiP, IMPMC, Université Pierre et Marie Curie, Paris)
    Thursday, April 10, 2014 - 10:30
    Room Aurigny
    Talk abstract: 

    Il existe plusieurs modèles pour décrire le repliement des protéines, c’est à dire la formation d’un globule compact après la synthèse de la chaîne peptidique dans le ribosome. Parmi ceux-ci, le modèle de nucléation-condensation stipule que sous l’effet de l’agitation thermique, des fluctuations du squelette mettent en contact des acides aminés répartis le long de la séquence. Ils constituent alors le noyau du repliement et nous nous intéressons à leur prédiction à partir de la séquence, par une simulation du repliement dans un espace discret avec une technique de Monte Carlo. Nous avons appelé MIR (Most Interacting Residues) les positions occupées par des acides aminés engagés dans un grand nombre de contacts non covalents. Leur comparaison avec les données expérimentales sera présentée.

  • Formalisation de réseaux de signalisation en logique

    Christine Froideveaux (LRI - INRIA AMIB - Université Paris Sud )
    Thursday, March 27, 2014 - 10:30
    Room Aurigny
    Talk abstract: 

    Dans la première partie de l'exposé nous présenterons une méthode basée sur la connaissance du domaine, qui permet de construire la topologie de réseaux moléculairesen exploitant des données expérimentales et des règles générales de raisonnement fournies par des experts.Nous montrerons comment cette méthode appliquée à des réseaux de signalisation permet de découvrir de nouvelles relations dans le réseau FSH.Dans une deuxième partie, nous introduirons une traduction du langage standard Systems Biology Graphical Notation Activity Flow (SBGN-AF) en programmation logique. Nous montrerons comment cette traduction peut être utilisée pour analyser la dynamique des réseaux SBGN-AF.

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