Previous seminars – 2013

(archives from old symbiose site)

 

  • EXOCANCER : Recherche par exome de nouveaux gĂšnes de prĂ©disposition en oncogĂ©nĂ©tique
    Marie de Tayrac (IGDR, Rennes1)
    Thursday, December 12, 2013 – 10:30
    Room Aurigny
    Talk abstract: 

    Lors des consultations d’oncogĂ©nĂ©tique, la recherche des gĂšnes de prĂ©disposition aux cancers est proposĂ©e dans le cadre d’une histoire familiale lourde ou de la survenue d’un cancer rare ou Ă  un Ăąge inappropriĂ©. Pour 85% des patients, les rĂ©sultats de ces recherches sont non-concluants et traduisent l’existence de gĂšnes de prĂ©disposition encore inconnus Ă  ce jour. A l’heure actuelle, le dĂ©veloppement des technologies de sĂ©quençage nouvelle gĂ©nĂ©ration ouvre la possibilitĂ© d’étendre systĂ©matiquement cette recherche Ă  l’ensemble des sĂ©quences codantes du gĂ©nome (exome). Ce type d’analyse s’avĂšre en effet particuliĂšrement adaptĂ© Ă  la dĂ©couverte de nouveaux gĂšnes impliquĂ©s dans ces situations et par consĂ©quent permettra l’amĂ©lioration de la prise en charge des patients et de leurs familles. Ainsi, nous dĂ©veloppons deux approches, l’une vise Ă  identifier les variants gĂ©nĂ©tiques en cause dans la survenue de cancers sporadiques rares chez l’adulte jeune ou chez l’enfant (recherche de mutation de novo par Ă©tude de trio pĂšre-mĂšre-enfant) ; l’autre s’appuie sur l’étude de rares cas de famille possĂ©dant plusieurs membres atteints de tumeurs cĂ©rĂ©brales particuliĂšrement agressives, afin d’identifier les variants gĂ©nĂ©tiques en cause dans la survenue de ces tumeurs. En parallĂšle de ces recherches sur l’ADN constitutionnel des patients et de leur famille, nous Ă©tudions l’ADN somatique des patients afin d’établir une cartographie des altĂ©rations caractĂ©ristiques de leur tumeur (SNVs, INDELs, CNVs, LOH, translocations
). La combinaison de ces diffĂ©rentes approches fournira une meilleure comprĂ©hension des voies molĂ©culaires impliquĂ©es dans l’initiation tumorale et permettra l’amĂ©lioration du conseil gĂ©nĂ©tique par la mise au point de tests diagnostiques Ă©tendus, mais Ă©galement, l’orientation des patients vers une thĂ©rapeutique ciblĂ©e, si elle existe.  

  • Sensitive detection of large structural variants in the tumor samples: from algorithms to the detection of chromothripsis in neuroblastoma.
    Valentina Boeva (Inserm / Curie)
    Thursday, December 5, 2013 – 10:30
    Room Aurigny
    Talk abstract: 

    In addition to point mutations, cancer genomes often display large genetic abnormalities: copy number alterations (CNAs) and structural variants (SVs) (Hanahan and Weinberg, 2011). Genetic abnormalities in specific regions may be related to the aggressiveness of a cancer and be associated with clinical outcomes. In cancer, tumor suppressor genes can be deleted or mutated, whereas oncogenes can be amplified or mutated with a gain of function. At the same time, translocations can result in cancer-causing fusion proteins (BCR/ABL fusion in CML, BCL1/IGH in multiple myeloma, EWS/FLI1 in Ewing sarcoma, etc.)
    With the arrival of new high-throughput sequencing technologies, our current power to detect genetic abnormalities has significantly improved. Genomic breakpoints of large structural variants (i.e., translocations or large duplications and deletions) can be identified using two complementary approaches: (1) analysis of ‘discordant’ mate-paired/paired-ends mappings (PEMs) and (2) calculation segmentation of copy number and allelic content profiles and.
    To analyze PEM data, we developed a clustering-based approach SVDetect [2]. SVDetect finds clusters of ‘abnormal’ PEMs and uses all the characteristics of reads inside the clusters (orientation, order and clone insert size) to identify structural variant type. SVDetect allows identification of a large spectrum of rearrangements including large insertions-deletions, duplications, inversions, insertions of genomic shards and balanced/unbalanced intra/inter-chromosomal translocations. It calculates several parameters of reads inside putative SVs (e.g., percentage of discordant pairs) that allow the user to filter out false predictions.
    There is possibility to improve the selectivity of SVDetect predictions by combining SVDetect with Control-FREEC [3, 4] – our tool for identification of genomic regions of gain and loss. Control-FREEC is able to analyze over-diploid tumor samples and samples contaminated by normal cells. If sequencing coverage is large enough (>15x) Control-FREEC is able to calculate allelic content profiles and consequently predict loss of heterozygosity regions. The intersection of outputs produced by Control-FREEC and SVDetect allows (1) refining coordinates of CNAs using PEM data and (2) improving confidence in calling true positive rearrangements (particularly, in ambiguous satellite/repetitive regions).
    We applied this combined strategy to study SVs in neuroblastoma tumors [5]. Neuroblastoma is embryonal cancer of the sympathetic nervous system observed in early childhood. Structural chromosome aberrations are recurrently observed in aggressive cases of neuroblastoma. In this study, we investigated somatic rearrangements in two neuroblastoma cell lines and two primary tumors using paired-end sequencing of mate-pair libraries. In one cell line and in the two primary tumors, this approach confirmed the localization of the majority of rearrangements within one or two chromosomes, consistent with the phenomenon of chromothripsis. We further characterized 51 rearrangements at the base pair resolution. We concluded that both non-homologous end joining-mediated repair and replicative processes may account for genomic rearrangements in neuroblastoma.
    References
    1. Hanahan, D. and Weinberg, R.A. (2011) Hallmarks of cancer: the next generation, Cell, 144, 646-674.
    2. B. Zeitouni et al. (2010) SVDetect – a bioinformatic tool to identify genomic structural variations from paired-end next-generation sequencing data, Bioinformatics, 26: 1895-1896.
    3. V. Boeva et al. (2011) Control-free calling of copy number alterations in deep-sequencing data using GC-content normalization, Bioinformatics, 27(2):268-9.
    4. V. Boeva et al. (2012) Control-FREEC: a tool for assessing copy number and allelic content using next generation sequencing data, Bioinformatics, 28(3):423-5.
    5. V. Boeva et al. (2013) Breakpoint features of genomic rearrangements in neuroblastoma with unbalanced translocations and chromothripsis. PLoS One. 8(8):e72182.

  • ExtrĂȘmophiles des fonds ocĂ©aniques & Assemblage des communautĂ©s microbiennes
    Lois Maignien & Mohamed Jebbar (UBO – ifremer)
    Thursday, November 28, 2013 – 10:30
    Room Aurigny
    Talk abstract: 

    Deux exposés:

    Les microorganismes extrĂȘmophiles des fonds ocĂ©aniques : diversitĂ© et intĂ©rĂȘt

    Prof. Mohamed JEBBAR

    Laboratoire de Microbiologie des environnements extrĂȘmes UMR 6197, UBO-CNRS-Ifremer, IUEM, place Nicolas Copernic, Technopole Brest-Iroise, 29280 PlouzanĂ©, France,

    TĂ©l : +33 298 498 817, Email :  mohamed.jebbar@univ-brest.fr ; web : http://wwz.ifremer.fr/umr6197/

     

    Depuis une vingtaine d’annĂ©es, le Laboratoire de Microbiologie des Environnements extrĂȘmes (LM2E, Brest) a explorĂ© les environnements ocĂ©aniques profonds et Ă©tudiĂ© les communautĂ©s microbiennes associĂ©es. Dans un premier temps il s’est intĂ©ressĂ© aux sources hydrothermales et depuis une dizaine d’annĂ©es il a Ă©tendu son champ d’investigation aux zones d’émission de fluides froids (des marges continentales, actives et passives) et aux sĂ©diments marins profonds. Outre la profondeur, et donc l’omniprĂ©sence du paramĂštre pression, ces environnements ont en commun d’ĂȘtre pratiquement indĂ©pendants de l’énergie solaire et de la production primaire photosynthĂ©tique. Certes, l’oxygĂšne des fonds ocĂ©aniques provient de la photosynthĂšse, mais les procaryotes de ces Ă©cosystĂšmes basĂ©s sur la chimiosynthĂšse microbienne utilisent frĂ©quemment d’autres accepteurs d’électrons. De mĂȘme, la matiĂšre organique enfouie dans les sĂ©diments profonds a une origine photosynthĂ©tique, mais il s’agit d’un stock ancien et non d’un apport contemporain. Enfin, certains microorganismes chimio-litho-autotrophes utilisent des sources d’énergie comme l’hydrogĂšne, dont une partie est d’origine abiotique. Le LM2E a dĂ©crit une centaine d’espĂšces d’Archaea et de Bacteria issues principalement des sources hydrothermales. Il dispose d’une collection de 407 espĂšces et isolats d’Archaea et 693 espĂšces et isolats de Bacteria. Parmi les espĂšces dĂ©crites ou co-dĂ©crites par le LM2E et les laboratoires prĂ©existants, plusieurs souches ont prĂ©sentĂ©, soit du fait de leur position dans l’arbre du vivant, de leur rĂ©sistance Ă  des conditions extrĂȘmes ou de leur intĂ©rĂȘt biotechnologique potentiel, suffisamment d’intĂ©rĂȘt pour voir leur gĂ©nome complĂštement sĂ©quencĂ© (Pyrococcus abyssi, Thermococcus gammatolerans, Thermococcus barophilus MP, Thermococcus sp TV2, Thermococcus barophilus CH1 et CH5, Pyrococcus yayanosii, Palaeococcus pacificus, Marinitoga piezophila).

     

    MĂ©canismes d’assemblage des communautĂ©s microbiennes : des communautĂ©s aux gĂšnes fonctionnels.

    LoĂŻs Maignien

    Maitre de conférence

    Laboratoire de microbiologie des environnements extrĂȘmes

    Université de Brest.

     

               «Tout est partout, mais l’environnement sĂ©lectionne» Cette citation de Baas-Becking (1934) est une idĂ©e fondatrice de l’écologie et de la biogĂ©ographie microbienne. L’intĂ©gration des NGS Ă  la microbiologie environnementale, 80 ans plus tard, permet d’aborder ce type de question et mieux comprendre les mĂ©canismes Ă©cologiques qui contrĂŽlent la structure et la dynamique des communautĂ©s microbiennes. Nous avons utilisĂ© la phyllosphere (les communautĂ©s associĂ©es aux parties aĂ©riennes des plantes) afin de dĂ©terminer la contribution relatives de mĂ©canismes dĂ©terministes, tels que les paramĂštres environnementaux dont la prĂ©valence est suggĂ©rĂ©e par Baas-Becking, mais aussi des processus stochastiques ou neutres, lors de l’assemblage de communautĂ©s microbiennes fonctionnelles.  L’analyse d’une sĂ©rie temporelle de 70 jours sur 32 plantes (Arabidopsis thaliana) a montrĂ© une convergence de la composition de la phyllosphere avec le temps, confirmant un rĂŽle du recrutement sĂ©lectif par l’hĂŽte au sein du microbiome de l’air. Cependant, l’abondance relative de chacun des taxa spĂ©cifiques de la phyllosphere est distribuĂ© de façon plus alĂ©atoire, et dĂ©pend des chemins de dispersion via l’air. Le concept de metacommunautĂ© permet de mieux expliquer le dĂ©veloppement, Ă  pression sĂ©lective Ă©gale, de communautĂ©s microbiennes diffĂ©rentes. De telles structures alternatives de communautĂ©s suggĂšrent que la sĂ©lection par l’hĂŽte pourrait se faire moins au niveau des organismes que des gĂšnes fonctionnels bactĂ©riens qui les composent. AprĂšs avoir comparĂ© la structure des communautĂ©s de la phyllosphere, nous avons donc sĂ©quencĂ© 23 metagenomes issus de cette sĂ©rie temporelle, et travaillons actuellement sur les mĂ©thodes de comparaison de metagenomes Ă  partir des sĂ©quences brutes, de leur assemblage en contigs, ou de leur annotation fonctionnelles.

               Ces questions Ă©cologiques, ainsi que les mĂ©thodes dĂ©veloppĂ©es dans le cadre de ce projet, seront appliquĂ©es Ă  l’étude de l’assemblage des communautĂ©s extrĂȘmophiles dans les grands fonds marins au sein du LM2E de Brest.

    • 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 numĂ©riques – une nouvelle approche pour Ă©tudier l’organisation des systĂšmes biologiques
      Guillaume Beslon, INSA-Lyon, Ă©quipe INRIA Beagle
      Thursday, May 23, 2013 – 10:30
      Room Aurigny
      Talk abstract: 

      Au cours de ce sĂ©minaire, je prĂ©senterai les approches de “gĂ©nĂ©tique numĂ©rique” (digital genetics) afin de montrer comment elles peuvent ĂȘtre utilisĂ©es pour comprendre l’origine Ă©volutive des structures gĂ©nomiques et transcriptomiques. Je prĂ©senterai en particulier le modĂšle aevol, dĂ©veloppĂ© par l’Ă©quipe INRIA Beagle Ă  Lyon pour modĂ©liser l’Ă©volution des organismes bactĂ©riens, ainsi que les principaux rĂ©sultats biologiques obtenus Ă  ce jour. Enfin, je concluerai par une rĂ©flexion plus gĂ©nĂ©rale sur l’usage de modĂšles 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 gĂ©nome dĂ©voile-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 Ă©tudes ont montrĂ© que l’architecture des gĂ©nomes et les interactions entre les chromosomes jouent un rĂŽle dans la rĂ©gulation de l’expression des gĂšnes. Dans ce contexte, nous avons formulĂ© l’hypothĂšse suivante : la structure du gĂ©nome affectant l’expression des gĂšnes, l’étude de l’expression des gĂšnes devrait permettre d’accĂ©der Ă  cette structure. Nous avons donc dĂ©veloppĂ© une mĂ©thode in silico, basĂ©e sur les statistiques multivariĂ©es et permettant d’explorer la co-expression entre gĂšnes. RĂ©utilisant des donnĂ©es d’expression disponibles, cette mĂ©thode a permis la mise en Ă©vidence, Ă  l’échelle d’un gĂ©nome entier, de groupes de gĂšnes co-localisĂ©s et co-exprimĂ©s. Ces donnĂ©es de co-expression ont ensuite Ă©tĂ© comparĂ©es Ă  des donnĂ©es d’interactions physiques. Nous avons observĂ© que de nombreux gĂšnes co-exprimĂ©s interagissent physiquement, confortant ainsi notre hypothĂšse que la co-expression permet de dĂ©voiler une part de la structure du gĂ©nome 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 NĂšgre (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 protĂ©ines Ă  l’aide d’un alphabet structural
      Bernard Offmann (UFIP Université de Nantes)
      Thursday, March 14, 2013 – 10:30
      Room Aurigny
      Talk abstract: 

      L’Ă©tude des relations sĂ©quence-structure reprĂ©sente un enjeu majeur en modĂ©lisation molĂ©culaire. Classiquement, celle-ci repose sur une description du repliement d’une protĂ©ine en terme de structures secondaires, c’est Ă  dire, en terme d’hĂ©lices α et brins ÎČ qui reprĂ©sentent les motifs rĂ©guliers et les boucles qui reprĂ©sentent des motifs trĂšs variables. Or, ces derniĂšres reprĂ©sentent plus de 50% des structures des protĂ©ines. Par ailleurs, la description des structures 3D en structures secondaires souffre d’une certaine absence de consensus en fonction des nombreuses mĂ©thodes utilisĂ©es et l’identification des limites des hĂ©lices et des brins reste problĂ©matique (Offmann et al, 2007). Ainsi la description de l’Ă©tat du repliement d’une protĂ©ine en terme de ces trois Ă©tats (hĂ©lice, brin, boucle) est loin d’ĂȘtre satisfaisante, ce qui limite les perspectives de leurs utilisations pour l’Ă©tude des relations sĂ©quence-structure. De nouvelles approches pour la description des structures locales ont ainsi Ă©tĂ© dĂ©veloppĂ©es avec notamment la constitution de librairies de petits motifs structuraux rĂ©currents et la dĂ©finition d’alphabets structuraux.

      Je prĂ©senterai les applications autour de l’usage d’un alphabet structural, les blocs protĂ©iques (BPs). Cet alphabet structural est constituĂ© d’un ensemble de 16 petits prototypes structuraux  d’une longueur de 5 rĂ©sidus chacun qu’on reprĂ©sente par les lettres de a Ă  p. Ces fragments sont dĂ©finis comme des pentapeptides chevauchants, dĂ©crits par un vecteur de huit angles diĂšdres. J’exposerai le dĂ©veloppement d’une mĂ©thode pour la comparaison rapide des structures des protĂ©ines s’appuyant sur les mĂ©thodes d’alignement de sĂ©quences (Tyagi et al, 2006 ; 2008). Les dĂ©veloppements rĂ©cents autour des BPs pour la caractĂ©risation des structures locales et pour la reconnaissance du repliement seront abordĂ©s (Offmann et al soumis, Mahajan et al en prĂ©paration).

      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).
    • SĂ©quençage, assemblage et analyse du chromosome 3B du blĂ© tendre
      Frederic Choulet – INRA – UniversitĂ© Blaise Pascal – Clermont Ferrand
      Thursday, February 21, 2013 – 10:30
      Room Aurigny
      Talk abstract: 

      Le gĂ©nome du blĂ© tendre est hexaploĂŻde, composĂ© de 17 Gb (5x le gĂ©nome humain), et dont 85% dĂ©rivent d’Ă©lĂ©ments rĂ©pĂ©tĂ©s. Ces caractĂ©ristiques font que son sĂ©quençage reste un vĂ©ritable challenge mĂȘme en considĂ©rant les dĂ©bits des technologies actuelles. Afin de rĂ©duire cette complexitĂ©, une approche utilisant le tri de chromosomes et la construction de banques BAC ordonnĂ©es spĂ©cifiques de chacun des 21 chromosomes a Ă©tĂ© rĂ©alisĂ©e dans le cadre d’un consortium international (Int. Wheat Genome Sequencing Consortium). L’Equipe GENOME Ă  l’INRA de Clermont-Ferrand a Ă©tabli la premiĂšre carte physique d’un chromosome de blĂ© (le 3B, 1 Gb Ă  lui seul) en 2008 et, depuis 2010, la production d’une sĂ©quence de rĂ©fĂ©rence a Ă©tĂ© entreprise en combinant une approche de sĂ©quençage par pools de BAC (8500 BAC au total) et une approche chromosome entier. Je prĂ©senterai la stratĂ©gie employĂ©e et les outils mis en place pour parvenir Ă  assembler une pseudomolĂ©cule unique reprĂ©sentative du chromosome 3B. Les rĂ©sultats concernant la composition, l’organisation et l’Ă©volution du gĂ©nome de blĂ© seront Ă©galement discutĂ©s.

       
    • BioSpring : un outil de simulation interactive pour construire de grands ensembles biomolĂ©culaires
      Olivier Delalande (Université de Rennes 1)
      Thursday, February 7, 2013 – 10:30
      Room Aurigny
      Talk abstract: 

      Le programme de simulation molĂ©culaire BioSpring (co-dĂ©veloppement Rennes 1 + IBPC Paris + Univ. Paris XI) permet la manipulation interactive d’une ou plusieurs macromolĂ©cules biologiques modĂ©lisĂ©es par un « rĂ©seau Ă©lastique augmentĂ© » qui combine un rĂ©seau de ressorts et des interactions non-liantes entre pseudo-atomes. C’est un outil de dĂ©veloppement qui peut-ĂȘtre utilisĂ© comme « couteau suisse » et constructeur molĂ©culaire puissant, notamment pour prĂ©parer des simulations numĂ©riques ou pour concevoir des modĂšles molĂ©culaires compatibles avec des jeux de contraintes expĂ©rimentales (RMN, footprint, cross-link, cryo-microscopy, SAXS, etc). Les « expĂ©riences » BioSpring sont interactives et intuitives, qualitĂ©s remarquables pour des approches Ă  visĂ©e pĂ©dagogique. L’interactivitĂ© a nĂ©cessitĂ© des optimisations du code qui est parallĂ©lisĂ© avec OpenMP et portĂ© sur carte graphique (GPU) via OpenCL. Une gestion rapide et efficace des interactions non-liantes est rĂ©alisĂ©e grĂące Ă  une grille de potentiel. L’approche est flexible et permet des scĂ©narios multi-rĂ©solution combinant reprĂ©sentation tout atome et gros grain. Plusieurs exemples d’application Ă  des sujets de recherche de biologie fondamentale ou biomĂ©dicale seront prĂ©sentĂ©s. L’utilisation de BioSpring pour l’Ă©tude du systĂšme biomolĂ©culaire dont les dysfontionnements sont Ă  l’origine des myopathies sera exposĂ©e plus en dĂ©tail.  

       
    • Mise Ă  jour de rĂ©seaux d’automates
      Mathilde Noual (ENS Lyon)
      Thursday, January 31, 2013 – 10:30
      Room Aurigny
      Talk abstract: 

      Les rĂ©seaux d’automates que je considĂšre sont constituĂ©s d’automates s’incitant les uns les autres Ă  changer d’Ă©tat. Dans ces rĂ©seaux, “mettre Ă  jour” l’Ă©tat d’un automate revient Ă  lui imposer de se conformer aux influences qu’il reçoit alors de la part des (autres) automates du rĂ©seau. Et choisir un mode de mise Ă  jour pour l’ensemble des automates d’un rĂ©seau permet donc de sĂ©lectionner certains Ă©vĂ©nements, ou changements, parmi l’ensemble de ceux qui sont a priori possibles. Cela permet aussi d’organiser et d’ordonner les Ă©vĂ©nements les uns par rapport aux autres de façon, par exemple, Ă  imposer que des Ă©vĂ©nements indĂ©pendants se produisent simultanĂ©ment ou, du moins, de maniĂšre assez rapprochĂ©e pour qu’aucun autre Ă©vĂ©nement ne puisse se produire entre temps. Dans cet exposĂ©, je propose de s’intĂ©resser Ă  l’incidence de diffĂ©rents aspects du mode de mise Ă  jour d’un rĂ©seau sur son comportement global, au regard de l’incidence de sa structure. Et je propose de le faire avec des automates Ă  deux Ă©tats de façon Ă  capturer l’essence primaire de ce problĂšme.

       
    • TBA
      Alejandro Maass (Center for Genome Regulation, Université du Chili)
      Wednesday, January 30, 2013 – 10:30
      Room Aurigny
      Talk abstract: 

      TBA

       
    • Exploration du rĂ©seau d’interactions impliquĂ© dans la maintenance gĂ©nomique de l’Archaea hyperthermophile Pyrococcus Abyssi.
      Pierre François Pluchon (Ifremer, Brest)
      Thursday, January 24, 2013 – 10:30
      Room Aurigny
      Talk abstract: 

       

      La rĂ©plication, la rĂ©paration et la recombinaison de l’ADN sont des processus essentiels au sein de chaque cellule. La fidĂ©litĂ© de la rĂ©plication est indispensable au maintien de l’information gĂ©nĂ©tique et la conservation de l’intĂ©gritĂ© des chromosomes est nĂ©cessaire Ă  la survie des organismes. Chez les Archaea, les processus en charge de la rĂ©plication de l’ADN constituent une version simplifiĂ©e du systĂšme dĂ©crit chez les Eucaryotes. En revanche, la rĂ©paration des dommages reste Ă©nigmatique puisque les homologues de protĂ©ines essentielles de la rĂ©paration, identifiĂ©es chez les Eucaryotes ou les BactĂ©ries, n’ont Ă©tĂ© que partiellement identifiĂ©s au sein des gĂ©nomes Archaea. L’absence apparente de protĂ©ines de la rĂ©paration de l’ADN est encore plus singuliĂšre pour les espĂšces Archaea hyperthermophiles vivants dans des environnements oĂč la tempĂ©rature extrĂȘme (100°C) catalyse les dommages de l’ADN. Il est probable que la recherche et la caractĂ©risation de nouveaux acteurs de la maintenance gĂ©nomique chez ce type d’organismes permette la dĂ©couverte de nouvelles protĂ©ines ou de nouvelles voies mĂ©taboliques de la rĂ©paration de l’ADN.

      Un protocole de purification d’affinitĂ© couplĂ© une analyse en spectromĂ©trie de masse a permis d’identifier les partenaires de protĂ©ines impliquĂ©es dans la maintenance gĂ©nomique de l’Archaea hyperthermophile Pyrococcus Abyssi. Les interactions identifiĂ©es ont permis la construction du premier rĂ©seau d’interactions protĂ©ine – protĂ©ine de la maintenance gĂ©nomique Archaea.

      L’analyse topologique du rĂ©seau a menĂ© Ă  l’identification de nouvelles protĂ©ines ainsi que de nouvelles interactions entre des protĂ©ines essentielles de la maintenance gĂ©nomique, conservĂ©es avec les Eucaryotes. Plusieurs interactions ont Ă©tĂ© vĂ©rifiĂ©es indĂ©pendamment ou caractĂ©risĂ©es fonctionnellement in vitro ou in vivo. Ces travaux mettent Ă©galement en lumiĂšre l’étroite collaboration entre la rĂ©plication et la recombinaison de l’ADN et rĂ©vĂšlent de nouveaux aspects de la machinerie de transcription. 

       
    • Algorithmic and Compact Data Structures for NGR & NGS
      Guillaume Blin (IGM, Université de Marne la Vallée)
      Thursday, January 17, 2013 – 10:30
      Room Aurigny
      Talk abstract: 
      In this talk, we will address two different topics. In a first part, we will present the succinct data structure of wavelet tree and its usefulness for "Next Generation Sequencing". Wavelet tree is a succinct data structure used to efficiently store strings over an alphabet sigma in compressed space that support Access(x), Rank(y,x) and Select(y,x) operations in O(log(|sigma|)) time. Access(x) returns the character at position x while Rank(y,x) returns the number of occurences of character y before position x. Finally, Select(y,x) returns the position of the xth occurence of character y. After presenting the basics of wavelet trees, we will show how it can be used to efficiently index reads for assembly purpose. In a second part, we will present some algorithmic results on the "Next Generation Radiotherapies". Radiation therapy is one of the commonly used cancer therapies. The radiation treatment poses a tuning problem: the radiation needs to be effective enough to destroy the tumor, but it should maintain the functionality of the organs close to the tumor (organs at risk). Towards this goal, the design of radiation treatment has to be customized for each patient. We will mainly focus on Intensity Modulated Radiation Therapy using Multi-Leaf Collimator and on Brachytherapy and give some algorithmic results we recently achieved.
       
    • Towards Holistic Analyses of Metagenomic Data
      Mihai Pop (Center for Bioinformatics and Computational Biology, University of Maryland)
      Thursday, January 10, 2013 – 15:00 to 16:00
      Room Aurigny
      Talk abstract: 


      Moving from a DNA sample to a biological interpretation of the information provided by the microbiome entails many experimental and computational steps. Often, these analytical procedures are being developed one at a time, in isolation from the other components of the experimental and analysis pipeline.  As the field is starting to mature, and the scientific questions we want to ask of the microbiome are becoming more clear, it is becoming possible to explore how the individual parts of the analysis affect each other, and to develop the experiment and analysis simultaneously with the goal of extracting maximal information from the microbiome data.   In my talk I will discuss several efforts in my lab in this direction, primarily related to genomic and metagenomic assembly.  Time permitting I will also touch upon issues related to association statistics and dynamic modeling of microbial communities.

      Bio:
      Mihai Pop is an Associate Professor in the Department of Computer Science and the Center for Bioinformatics and Computational Biology at the University of Maryland, College Park.  He received his Ph.D. from Johns Hopkins University in 2000 and has been a Bioinformatics Scientist at The Institute for Genomic Research (TIGR) until 2005 when he joined the University of Maryland.  Dr. Pop’s research focuses on computational analyses of genomic data (primarily sequencing and mapping data) with specific applications in sequence assembly, sequence alignment, and metagenomics.

       

 

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