Symbiose seminars

  • F2C2: a fast tool for the computation of flux coupling in genome-scale metabolic networks.

    Abdelhalim Larhlimi (Université de Nantes)
    Thursday, November 14, 2013 - 10:30
    Room Aurigny
    Talk abstract: 

    Flux coupling analysis (FCA) has become a useful tool in the constraint-based analysis of genome-scale metabolic networks. FCA allows detecting dependencies between reaction fluxes of metabolic networks at steady-state. On the one hand, this can help in the curation of reconstructed metabolic networks by verifying whether the coupling between reactions is in agreement with the experimental findings. On the other hand, FCA can aid in defining intervention strategies to knock out target reactions.
    In my talk, I will present  F2C2, a fast tool for the computation of flux coupling in genome-scale metabolic networks.  F2C2, which is freely available at https://sourceforge.net/projects/f2c2/files/, is orders of magnitude faster than previous approaches. As a consequence, FCA of genome-scale metabolic networks can now be performed in a routine manner.

  • New algorithm to describe mathematically genetic inclusions in discrete time

    Alexandra Fronville (LabSticc - CERV - Equipe IHSEV)
    Thursday, October 24, 2013 - 10:30
    Room Aurigny
    Talk abstract: 

    During embryonic development tissues differentiate, deform, and move in a co-ordinated
    manner to generate various biological shapes. The orientation of the division plane is a key
    element in the generation of the multi-cellular shape. Morphogenesis can be seen as a
    morphological regulation system problem where the goal is to find the update rules for a 3-
    dimensional multi-cellular system which converges to a target shape.
    This can be viewed mathematically as a controlled, multi-valued, dynamic system which
    adapts shape according to environment. The proposed multi-cellular development model is
    designed and based on morphological analysis which will study the robustness of cellular
    development.
    We present an algorithm based on this model, in a virtual 3D-environment. Each cell has a
    dynamic dependant on the reading ability of the virtual genome and by the complex interplay
    between genetic, epigenetic, and environmental factors.
    Using this method we propose a genome for Wolpert’s French Flag Model and another for
    gastrulation. Exploring this cellular dynamic we will need to determine the different shapes
    that can develop from one single cell; and to find the code for a given shape. This inverse
    problem needs a morphological analysis tools like capture basin algorithm, or a viability
    algorithm for morphological equations. Parallel computing will be required to manage the
    complex outcomes of implementing these tools.

  • Interrogating RNA heterogeneity. RNASeq in the ENCODE project.

    Roderic Guigo (CRG, Barcelone - Bioinformatics and Genomics leader)
    Friday, June 21, 2013 - 10:00 to 12:00
    Amphi - Conference center - INRIA.
    Talk abstract: 
    The unfolding of the instructions encoded in the genome is triggered by the transcription of DNA into RNA, and the subsequent processing of the resulting primary RNA transcripts into functional mature RNAs. RNA is thus the first phenotype of the genome, mediating all other phenotypic changes at the organism level caused by changes in the DNA sequence. While current technology is too primitive to provide accurate measurements of the RNA content of the cell, the recent development of Massively Parallel Sequencing Instruments has dramatically increased the resolution with which we can monitor cellular RNA. Using these instruments, the ENCODE project has surveyed the RNA content of multiple cell lines and subcellular compartments. The results of these surveys underscore pervasive transription, as well as great RNA heterogeneity between and within cells. Comparison of RNA surveys with other genome wide epigenetic surveys—such as those of binding sites for Transcription Factors, or of Histone modifications—reveals a very tightly coupling between the different pathways involved in RNA processing,   transcription and splicing in particular.  Overall, the recent large scale transcriptome and epigenome surveys reveal that large portions of the genome exhibits some sort of biochemical activity. What fraction of this activity can be associated to biological function remains an open question

     

  • Evolution d'organismes numériques - une nouvelle approche pour étudier l'organisation des systèmes biologiques

    Guillaume Beslon, INSA-Lyon, équipe INRIA Beagle
    Thursday, May 23, 2013 - 10:30
    Room Aurigny
    Talk abstract: 

    Au cours de ce séminaire, je présenterai les approches de "génétique numérique" (digital genetics) afin de montrer comment elles peuvent être utilisées pour comprendre l'origine évolutive des structures génomiques et transcriptomiques. Je présenterai en particulier le modèle aevol, développé par l'équipe INRIA Beagle à Lyon pour modéliser l'évolution des organismes bactériens, ainsi que les principaux résultats biologiques obtenus à ce jour. Enfin, je concluerai par une réflexion plus générale sur l'usage de modèles et des simulations en biologie.

     

     

  • Digging in the dark matter of the Arabidopsis thaliana genome

    Hadi Quesneville (INRA, Versailles)
    Thursday, April 18, 2013 - 10:30
    Room Aurigny
    Talk abstract: 

    The characterization of repeated and repeat-derived sequences in genomes (collectively referred to as the repeatome) is of primary importance for the comprehension of genome evolution and species adaptation. We present the concepts and results from a series of repeatome characterization of the plant model A. thaliana, (i) combining different de novo repeat identification programs, (ii) performing successive iterations using whole repeatomes as input, (iii) taking advantage of the repeats that we identified in six other Brassicaceae species. Our work enables to significantly increase the determination of the A. thaliana repeatome.
    Further analyses of our results allow us to determine that the majority of the A. thaliana repeatome is rather ancient and likely to derive from the retention of fragments deposited by massive bursts that occurred early during the Brassicaceae evolution. Our work supports the relevance of such approaches, scraping an additional layer of ancestral repeated sequences, digging in the dark matter of the A. thaliana genomes, thereby adding to our knowledge of the nature and evolution of eukaryotic genomes.

  • L’expression du génome dévoile-t-elle sa structure ? Un exemple d’e-science

    Christian DIOT (INRA, UMR Pegase, Saint-Gilles)
    Thursday, April 11, 2013 - 10:30
    Room Aurigny
    Talk abstract: 

    De nombreuses études ont montré que l’architecture des génomes et les interactions entre les chromosomes jouent un rôle dans la régulation de l’expression des gènes. Dans ce contexte, nous avons formulé l'hypothèse suivante : la structure du génome affectant l’expression des gènes, l’étude de l’expression des gènes devrait permettre d’accéder à cette structure. Nous avons donc développé une méthode in silico, basée sur les statistiques multivariées et permettant d'explorer la co-expression entre gènes. Réutilisant des données d’expression disponibles, cette méthode a permis la mise en évidence, à l’échelle d’un génome entier, de groupes de gènes co-localisés et co-exprimés. Ces données de co-expression ont ensuite été comparées à des données d’interactions physiques. Nous avons observé que de nombreux gènes co-exprimés interagissent physiquement, confortant ainsi notre hypothèse que la co-expression permet de dévoiler une part de la structure du génome et ouvrant de nombreuses perspectives

     

     

  • Simulating molecular motions with robotics-inspired algorithms

    Juan Cortes (LAAS - CNRS, Toulouse)
    Thursday, April 4, 2013 - 10:30
    Room Aurigny
    Talk abstract: 

    The development of methods to compute feasible motions for a system in a physical workspace is an active field of research in robotics since the 70s. Sampling-based algorithms developed in this field during the last decade are efficient and general techniques for exploring constrained high-dimensional spaces. Such algorithms have been successfully applied to challenging problems in diverse domains beyond robotics, including computational structural biology. In this talk, I will give an overview of recent works carried out at LAAS-CNRS in this domain. In particular, I will present robotics-inspired algorithms for simulating protein conformational transitions, and protein-ligand access/exit pathways. The presentation will also show encouraging results on interesting systems such as enzymes and transmembrane proteins.

  • Tara Oceans - First insights into a large scale global oceanic microscopic eukaryote exploration.

    Eric Pelletier (CEA / Genoscope)
    Thursday, March 28, 2013 - 10:30
    Room Aurigny
    Talk abstract: 
    The Tara Oceans project summarizes about 3 years of marine waters sampling all over the Earth, scratching the surface of a globally yet ignored part of the living world, but a key player in most of the biogeochemical major cycles : the eukaryote plankton. With aboundances reaching more that 10 billions organisms per liter of sea water, and being responsible of about 50% of the overall atmospheric CO2 compartment, describing and understanding these organisms is of outmost importance.
    
    By combining several approaches (genomics, oceanography, physics, chemistry, imaging and informatics), this project is a large and truly interdisciplinary adventure. Constraining to the genomics part only, the huge amount of sequences generated faces us with the need of new tools to distangle these data.
    
    I'll give a global overview of the Tara Oceans goals and organisation, and provides insights into the first results that come out of this fantastic project.
    
  • Genetic and epigenetic signatures of regulatory elements: impact in development and evolution

    Nicolas Nègre (INRA, Montpellier)
    Thursday, March 21, 2013 - 10:30
    Room Aurigny
    Talk abstract: 

    Classical examples of transcriptional regulatory elements come from studies in Drosophila melanogaster. However, even after the sequencing of its genome, published in 2000 and completed in 2006, it was not clear that those principles could be applied genome-wide. The modENCODE project seeks to systematically annotate different categories of regulatory elements in the genome of Drosophila. Insulators, enhancers, silencers and promoters have been identified using epigenetic signatures of their activity and their genome-wide function has been studied by genetic as well as computational assays. It became clear that epigenetics play a major role in ensuring that the genetic program is effected correctly during development. However, little is known about the impact of epigenetic phenomenon on evolution processes. It is indeed hard to differentiate genetic contribution to phenotypes from epigenetic contribution. In fact, very little is known about the variation associated to epimutations. We seek to characterize such variation in a noctuid pest Spodoptera frugiperda. This Lepidopteran is found in North and South America as two sympatric strains that can only be differentiated by their host-plant preference: either corn or rice. Since these two plants have been introduced only recently in the habitat by agriculture, it is very likely that they reveal two incipient species, diverging because of their adaptation to host-plant. Such a short time of divergence mostly due to only one selective force is the ideal situation if one wants to find epimutations linked to differentially expressed genes.
     

  • Analyse des structures des protéines à l'aide d'un alphabet structural

    Bernard Offmann (UFIP Université de Nantes)
    Thursday, March 14, 2013 - 10:30
    Room Aurigny
    Talk abstract: 

    L'étude des relations séquence-structure représente un enjeu majeur en modélisation moléculaire. Classiquement, celle-ci repose sur une description du repliement d'une protéine en terme de structures secondaires, c'est à dire, en terme d'hélices α et brins β qui représentent les motifs réguliers et les boucles qui représentent des motifs très variables. Or, ces dernières représentent plus de 50% des structures des protéines. Par ailleurs, la description des structures 3D en structures secondaires souffre d'une certaine absence de consensus en fonction des nombreuses méthodes utilisées et l'identification des limites des hélices et des brins reste problématique (Offmann et al, 2007). Ainsi la description de l'état du repliement d'une protéine en terme de ces trois états (hélice, brin, boucle) est loin d'être satisfaisante, ce qui limite les perspectives de leurs utilisations pour l'étude des relations séquence-structure. De nouvelles approches pour la description des structures locales ont ainsi été développées avec notamment la constitution de librairies de petits motifs structuraux récurrents et la définition d'alphabets structuraux.

    Je présenterai les applications autour de l'usage d'un alphabet structural, les blocs protéiques (BPs). Cet alphabet structural est constitué d'un ensemble de 16 petits prototypes structuraux  d'une longueur de 5 résidus chacun qu'on représente par les lettres de a à p. Ces fragments sont définis comme des pentapeptides chevauchants, décrits par un vecteur de huit angles dièdres. J'exposerai le développement d'une méthode pour la comparaison rapide des structures des protéines s'appuyant sur les méthodes d'alignement de séquences (Tyagi et al, 2006 ; 2008). Les développements récents autour des BPs pour la caractérisation des structures locales et pour la reconnaissance du repliement seront abordés (Offmann et al soumis, Mahajan et al en préparation).

    Références
    Manoj Tyagi, Venkataraman S. Gowri, Narayanaswamy Srinivasan, Alexandre G. de Brevern, & Bernard Offmann. A substitution matrix for structural alphabet based on structural alignment of homologous proteins and its applications. Proteins : Struct. Func. Bioinf. 65(1) :32-39, 2006.
    Offmann B., Tyagi M., de Brevern A.G. Local Protein Structures, Current Bioinformatics, 2, 165-202, 2007.
    Tyagi M., de Brevern A.G., Srinivasan N., Offmann B. Protein structure mining using a structural alphabet, Proteins 71:920–937, 2008. 
    Offmann B.*, Mahajan S*., Tyagi M., de Brevern A.G., Srinivasan N., Cadet F.  PB-PENTAPEPT: a platform to investigate the structural features of pentapeptides in protein structures (submitted).

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