Previous seminars – 2018

(archives from old symbiose site)

 

  • Microscopie de fluorescence quantitative pour l’imagerie fonctionnelle en cellules vivantes: vers une analyse Ă  haut contenu.
    Marc Tramier IGDR
    Thursday, December 20, 2018 – 10:30
    Room Aurigny
    Talk abstract: 

    La microscopie photonique est devenu un outil incontournable en biologie cellulaire pour quantifier la dynamique les interactions et les activitĂ©s des macromolĂ©cules biologiques. Je montrerais dans un premier temps les mĂ©thodes de FRET par FLIM qui nous permettent dans l’Ă©quipe de mesurer ces paramètres et comment nous intensifions nos efforts pour dĂ©velopper ces mesures en multiplex et dans un contexte de criblage Ă  moyen dĂ©bit. Un certain nombre de verrous comme la microscopie intelligente automatisĂ©e ou les analyses et modĂ©lisation des donnĂ©es quantitatives seront Ă©voquĂ©es. Notre vision Ă  long terme est de porter des applications de la microscopie quantitative vers la mĂ©decine personnalisĂ©e et tout indique que croiser les donnĂ©es quantitatives d’imagerie avec des donnĂ©es omiques se rĂ©vèle un challenge d’intĂ©rĂŞt dans ce contexte.

  • DĂ©veloppement et applications d’outils d’analyse mĂ©tagĂ©nomique des communautĂ©s microbiennes associĂ©es aux insectes
    Cervin_Guyomar
    Friday, December 7, 2018 – 14:00 to 16:00
    Amphithéatre du PNRB
    Talk abstract: 

    Les interactions entre un hĂ´te et sont microbiote sont omniprĂ©sentes, et jouent un rĂ´le clĂ© dans le fonctionnement de tous les organismes. L’essor des technologies de sĂ©quençage mĂ©tagĂ©nomique permet de dĂ©crire ces associations avec une dĂ©finition inĂ©galĂ©e, et permet d’analyser la structure, la fonction et l’histoire Ă©volutive de ces microbiotes. Cette thèse a pour objectif d’exploiter pleinement le potentiel de ces donnĂ©es dans le cas d’un insecte modèle dans l’étude des relations hĂ´te-microbiote : le puceron du pois. Ses rĂ©sultats s’inscrivent Ă  la fois sur le plan de la biologie et du dĂ©veloppement de nouvelles mĂ©thodes d’analyse des donnĂ©es mĂ©tagĂ©nomiques. L’étude de donnĂ©es de resĂ©quençage a d’abord permis la mise en Ă©vidence d’une diversitĂ© gĂ©nomique insoupçonnĂ©e chez les symbiotes de cette insecte, qui rĂ©sulte d’histoires Ă©volutives variĂ©es que nous avons dĂ©crites. En parallèle, nous proposons une approche innovante pour l’assemblage de gĂ©nomes Ă  partir de donnĂ©es mĂ©tagĂ©nomiques, qui s’appuie sur un gĂ©nome de rĂ©fĂ©rence existant pour faciliter et accĂ©lĂ©rer l’assemblage. Cette mĂ©thode s’avère particulièrement adaptĂ©e Ă  la reconstruction de variations structurales, comme illustrĂ© lors de l’assemblage de cassettes de virulence d’un bactĂ©riophage. Dans l’ensemble, ces travaux offrent des rĂ©sultats inĂ©dits sur le microbiote du puceron du pois, et prĂ©sente des outils susceptibles d’être appliquĂ©s Ă  des systèmes plus complexes.

  • Genome-resolved metagenomics and other stories
    Tom Delmont (Genoscope)
    Thursday, November 29, 2018 – 10:30 to 12:30
    Room Aurigny
    Talk abstract: 

    This presentation will describe the emerging tools of genome-resolved metagenomics developed within the bioinformatics platform anvi’o, and their application to two biological systems: (1) the Deepwater Horizon oil spill, (2) and the surface of the oceans.

    • Soutenance de thèse: Investigating host-microbiota cooperation with gap-filling optimization problems
      Clémence FRIOUX
      Monday, November 19, 2018 – 14:00
      Room MĂ©tivier
      Talk abstract: 

      Systems biology relies on computational biology to integrate knowledge and data, for a better understanding of organisms’ physiology. Challenges reside in the applicability of methods and tools to non-model organisms, for which data is limited, and more generally to host-microbiota systems. Understanding the interactions in the later is an objective of systems ecology. Metabolic networks are a useful solution to model them functionally. In this direction, several semantics exist and are at the core of metabolic network reconstruction, particularly for their refinement through gap-filling. Gap-filling is a combinatorial problem that aims at selecting reactions in databases to ensure the feasibility of a behaviour by the model. It is a very crucial step due to various pitfalls: model overfitting, false positive, choice of functionality semantics. This thesis aimed at better understand these limits and propose solutions to them. As a first results part, we benchmarked several gap-filling algorithms to assess the value of graph-based semantics with respect to the constraint based one. Then we propose a hybrid gap-filling method that reconciles both semantics. Finally, we extended the gap-filling problem towards the selection of communities and the screening of metabolic functions within large microbiotas. Problems modelled and solved during this PhD were applied to brown algae metabolism and to the human gut microbiota.

    • Looking inside the dark proteome universe. A tale on protein regions that do not correspond to protein domain families.
      Tristan Bitard Feildel (UPMC)
      Thursday, November 15, 2018 – 10:30 to 12:00
      Room Aurigny
      Talk abstract: 

      71% is the percentage of the Human proteins with at least one domain annotation (Pfam v31) and 45% is the percentage of Human protein amino acid sequences corresponding to a domain (set made of canonical proteins and isoforms). Surprisingly not much isn’it? And these percentages is for the Human proteome, the most (probably?) extensively studied Eukaryotic organisms even if a huge bias has been recently pointed out regarding which genes are studied or left out. To what correspond the remaining amino acids? Very often they are viewed as intrinsically disordered regions (IDRs) or proteins (IDPs), part or whole proteins that do not fold into a stable structure. In this presentation, I will present an other view on these proteins and protein regions. Particularly I will show that restricting sequence analyses to annotation from protein domain databases is a too stringent approaches as to be part of a protein domain databases, a sequence must either have been lucky enough to have a corresponding X-Ray/NMR structure or be conserved and old enough to be in many different proteins and different organisms. I will present two examples, an evolutionary analyses of novel (recent) protein domains on Insect and a comparative  analyses of the dark proteome from Uniprot/Swissprot, to illustrate that the dark proteome might not be as dark as thought, but as often it is a matter of which tools to use.Keywords: protein domain, intrinsically disordered domains, novel domain

    • Un aperçu des dĂ©fis informatiques et bioinformatiques de l’axe analyse structurale et mĂ©tabolomique 
      LĂ©a Cabioch (BioGenouest)
      Thursday, November 8, 2018 – 10:30
      Room Aurigny
      Talk abstract: 

      L’axe analyse structurale et mĂ©tabolomique s’intĂ©resse Ă  la caractĂ©risation de structures de composĂ©s chimiques et au profilage non ciblĂ© de composĂ©s prĂ©sents dans des matrices naturelles ou transformĂ©es, dans le domaine des sciences de la vie. Trois plates-formes composent cet axe : BIBS centrĂ©e sur les activitĂ©s de caractĂ©risation structurale de biopolymères Ă  diffĂ©rentes Ă©chelles et par diffĂ©rentes modalitĂ©s ; PHENOTIC centrĂ©e sur le phĂ©notypage d’objets vĂ©gĂ©taux par la bio-imagerie ; Corsaire, plate-forme multi-sites, spĂ©cialisĂ©e dans l’analyse de petites molĂ©cules par des approches ciblĂ©es et non ciblĂ©es dans les Ă©chantillons biologiques. L’activitĂ© des trois plates-formes fait appel Ă  des mĂ©thodes variĂ©es pour l’acquisition, le traitement et la gestion des donnĂ©es. Bien que les donnĂ©es soient acquises en quantitĂ© et en qualitĂ© plus Ă©levĂ©es, leur stockage/gestion ne semble pas poser de difficultĂ©s. En revanche, le traitement des donnĂ©es gĂ©nĂ©rĂ©es en grand nombre et leur intĂ©gration/fusion lorsqu’elles sont de natures diffĂ©rentes restent un frein consĂ©quent au travail des chercheurs. Cette difficultĂ© est d’autant plus prĂ©sente lorsqu’un effort d’harmonisation avec diffĂ©rents laboratoires est mis en place, voire avec la communautĂ© planĂ©taire.

    • PhD Defend – From reads to transcripts: de novo methods for the analysis of transcriptome second and third generation sequencing
      Camille Marchet – Irisa
      Friday, September 28, 2018 – 14:00
      Room MĂ©tivier
      Talk abstract: 

      The purpose of this thesis work is to allow the processing of transcriptome sequencing data, i.e. messenger RNA sequences, which reflect gene expression. More precisely, it is a question of taking advantage of the characteristics of the data produced by the new sequencing technologies, known as third generation (TGS). These technologies produce large sequences, which cover the total length of RNA molecules. This has the advantage of avoiding the sequence assembly phase, which was tricky, though necessary with the data generated by previous sequencing technologies called NGS. On the other hand, TGS data are noisy (up to 15% sequencing errors), requiring the development of new algorithms to analyze this data. The core work of this thesis consisted in the methodological development and implementation of new algorithms allowing the grouping of TGS sequences by gene, then their correction and finally the detection of the different isoforms of each gene.

    • Computing Birds Acoustic Social Network
      HĂ©di Soula (UPMC)
      Thursday, September 27, 2018 – 10:30
      Room Aurigny
      Talk abstract: 

      For public health, economical and environmental reasons, surveying of bird populations is a major issue because of their proximity with humans. We propose passive acoustic methods that allow to assess the social structure of wild-type population and estimate several parameters of social groups.  Whole population acoustic network assessment can be a powerful tool to analyze and study important social groups of birds. However studies have focused mostly on vocal communication between two individuals and little is known about properties emerging from an acoustical network where several individuals are involved. On the other hand, animal social network analysis relies on static graphs of proximity — proximal — and most of the time ignore more distal information such as acoustic network of whole groups. We propose several methods and results to assess such acoustic networks and model to explain their dynamics in relation to their known social structure. 

    • Epissage alternatif et modèles grammaticaux
      Aymeric Antoine-Lorquin
      Thursday, September 13, 2018 – 10:30
      Room Markov
      Talk abstract: 

      Les modèles grammaticaux permettent de modĂ©liser des motifs de sĂ©quences gĂ©nomiques, notamment en dĂ©crivant comment se structurent les diffĂ©rents Ă©lĂ©ments prĂ©sents au sein de ces motifs. Ces modèles semblent donc particulièrement adaptĂ©s pour la rechercher des transcrits alternatifs, qui rĂ©sultent de sĂ©lections diffĂ©rentes des exons d’un gène lors de l’Ă©pissage alternatif.Dans cet exposĂ©, je prĂ©senterai rapidement ce que sont les modèles grammaticaux. Je dĂ©crirai ensuite quelques travaux menĂ©s dans le cadre de ma thèse et de mon post-doc sur la recherche ex nihilo de transcrits alternatifs dans des sĂ©quences de gènes, la recherche de transcrits alternatifs basĂ©e sur l’information d’orthologie et enfin la recherche de transcrits alternatifs au sein de long-reads issus de sĂ©quençage nanopore.

  • Reference-free approach for population genomic analysis using metagenomic and metranscriptomic data
    Amin Madoui (Genoscope CEA)
    Thursday, July 5, 2018 – 14:00
    Room Aurigny
    Talk abstract: 

    The availability of large datasets of metagenomic sequences offers new opportunities for population genetics research. However, for many non-model species, the lack of reference genomes remains an important issue and constitutes an obstacle for population genomics studies. We took advantages of the discoSnp++ program and proved first its usefulness in the context of metagenomics. Then we developed a new reference-free method to identify species named metavariants species (MVS) by analogy to the metagenomic species (MGS). After detecting biallelic loci directly from metagenomic reads using discoSnp++, MVSs are identified by density-based clustering on biallelic loci depth sequencing coverage across all sampled populations. Then, the allele frequencies of MVS can be used for population genomic analyses to identify population differentiation and loci under natural selection. We applied this method to decipher population structure and differentiation on Tara Oceans metagenomic data. We also combined metatranscriptomic and metagenomic data with discoSnp++ to identify allele-specific expression (ASE) at the population level and detected a strong link between loci under natural selection and loci under ASE.

     

  • Spectral methods for reconstructing latent orderings, and applications to de novo genome assembly.
    Antoine Recanati (ENS)
    Thursday, June 28, 2018 – 10:30
    Room Aurigny
    Talk abstract: 

    The seriation problem seeks to recover a latent ordering from similarity information. We typically observe a matrix measuring pairwise similarity between a set of n elements and assume they have a serial structure, i.e. they can be ordered along a chain where the similarity between elements decreases with their distance within this chain. In the context of de novo prokaryotic genome assembly, within the Overlap-Layout-Consensus paradigm, we collect fragments of DNA (reads) randomly sampled across the genome, with sufficient coverage so that a given read overlaps with the neighboring reads. However, the position of the reads within the genome is unknown, so one has to solve a sort of jigsaw puzzle (the layout). This layout step can fit in the framework of Seriation, where the similarity measures the overlap (if any) between two reads, and we wish to reorder the reads such that two neighboring reads have a large overlap, and two reads far apart do not overlap.

    In this talk, I will present a basic spectral method for Seriation, akin to the Spectral Clustering method widely used in Machine Learning, together with a simple extension that allows to deal with circular orderings and improves robustness to noise. I will then present results of this method applied to finding the layout of E. coli reads sequenced with Oxford Nanopore Technology MinION device.

  • Thèses encadrĂ©es en bioinformatique
    Mourad Elloumi (univ. Tunis)
    Thursday, June 21, 2018 – 10:30
    Room Aurigny
    Talk abstract: 

    Dans cet exposé, je vais présenter les activités de notre groupe,
    le BioInformatics Group (BIG), à travers les thèses encadrées.

    Je présente, particulièrement, nos travaux sur :

    . Le Biregroupement des Données Biopuces

    . Correction des Données de Séquençage de 3ème Génération

    Je termine cet exposé, par présenter mes autres activités

  • Genome scale metabolic modeling and study of secondary metabolism of 24 Penicillium species
    Sylvain Prigent
    Thursday, May 31, 2018 – 10:30
    Room Aurigny
    Talk abstract: 

    During this presentation I will talk about my 3 years of Postdoc in Jens Nielsen lab in Sweden. Where I studied metabolism of Penicillium species. Modelling of metabolism at the genome scale have proved to be an efficient for explaining observed phenotypic traits in living organisms. Further, it can be used as a means of predicting the effect of genetic modifications e.g. for generation of microbial cell factories. With the increasing amount of genome sequencing data available, a need exists to accurately and efficiently generate such genome scale metabolic models (GEMs) of non-model organisms, for which there are few data. In this talk, I will present a semi-automatic reconstruction approach applied to 24 Penicillium species, which have potential for production of pharmaceuticals secondary metabolites or used in foods such as cheeses. The models were based on the MetaCyc database and a previously published Penicillium GEM, and gave rise to comprehensive genome scale descriptions of their metabolism. The models proved that while central carbon metabolism is highly conserved, secondary metabolic pathways represent the main diversity among the species. I will also present some work we did on prediction of production of secondary metabolites based on genomic sequence and some RNA-seq analysis on those 24 species.

    At the end of my presentation I will also talk a little about my current and future work on fruit biology at INRA Bordeaux.

     

  • BRAvo : A tool for regulatory network assembly through Linked Open Data
    Marie Lefebvre (LN2S (Nantes))
    Thursday, May 24, 2018 – 10:30
    Room Aurigny
    Talk abstract: 

    A few years ago, SyMeTRIC health actors have proposed personalized medicine approaches in the context of several pathologies or therapeutical approaches such as cancer, transplantation, cardiovascular, respiratory or metabolic diseases. In spite of pathological diversities, these actors share methodological and technological commonalities. In particular they strongly rely on the exploration and combination of several heterogeneous and massive biological and clinical datasets to discover multi-parameter pathological signatures and new biomarkers.

    In order to assemble data arising from different scales, technologies or localities, huge efforts address the organization of biological knowledge through linked open databases. These databases are supposed to be automatically queryable in order to reconstruct regulatory and signaling networks. Nevertheless, assembling networks usually implies manual operations due to source-specific identification of biological entities and relationships, multiple life-science databases with redundant information and difficulty to recover the logical flow of a biological pathway.

    In this talk, I will provide a framework based on Semantic Web technologies for automating the assembly of regulatory and signaling networks. To this purpose,  I developed BRAvo, an interactive web tool, allowing users to interact with the reconstruction process, and a command-line tool allowing to address larger scale models in a batch mode.

    Our results show that BRAvo is able to retrieve networks of 5000 nodes from 200 input genes by querying the full PathwayCommons database in less than one hour. BRAvo can also provide interesting filters of data sources, depth reconstruction and biological entities type. Thanks to BRAvo, we are now able to address issues of heterogeneous data integration for biological network reconstruction intended for computational and predictive models.

  • De la reconstruction de gĂ©nomes ancestraux vers l’aide Ă  l’assemblage
    Sèverine BĂ©rard (Institut des Sciences de l’Evolution – Montpellier)
    Thursday, May 17, 2018 – 10:30
    Room Minquiers
    Talk abstract: 

    Nous prĂ©senterons une mĂ©thode permettant de reconstruire des gĂ©nomes ancestraux dans un contexte phylogĂ©nĂ©tique. Cette approche retrace l’histoire Ă©volutive des adjacences de gènes en prenant en entrĂ©e les ordres de gènes dans les espèces actuelles et les arbres phylogĂ©nĂ©tiques des gènes et des espèces, et en optimisant un critère de parcimonie. L’algorithme sous-jacent est basĂ© sur le principe de programmation dynamique, ce qui permet de traiter de gros jeux de donnĂ©es en temps raisonnable. Plusieurs modifications de ce premier algorithme ont permis, entre autre, de reconstruire Ă  la fois les ordres de gènes ancestraux et actuels, permettant ainsi d’amĂ©liorer le scaffolding des gĂ©nomes actuels. La mĂ©thode est Ă©galement capable d’infĂ©rer des scores de confiance aux adjacences prĂ©dites et de prendre en entrĂ©e des donnĂ©es de sĂ©quençage appariĂ©es. Nous montrerons l’application de notre mĂ©thode sur un jeu de donnĂ©es de 18 moustiques Anopheles oĂą nous avons pu rĂ©duire le nombre de scaffolds de plus de 60 %. Cette mĂ©thode est implĂ©mentĂ©e dans le logiciel DeCoSTAR (http://pbil.univ-lyon1.fr/software/DeCoSTAR/get.html

  • Semantic Web of Linked Data
    Olivier Corby (Inria sophia/nice)
    Thursday, April 5, 2018 – 10:30
    Room Aurigny
    Talk abstract: 

    En introduction nous rappelons très brièvement les principes du Web sémantique et du Web de données.
    Puis nous présentons deux langages complémentaires issus de nos recherches sur le Web sémantique.
    Le premier langage est STTL, SPARQL Template Transformation Language. Il permet d’Ă©crire des transformations de graphes RDF vers des formats texte tels que Turtle, RDF/XML,  OWL functional syntax,  HTML, etc. 
    Le second est LDScript, Linked Data Script Language, un DSL dĂ©diĂ© Ă  la dĂ©finition de fonctions d’extension pour SPARQL qui ne nĂ©cessite pas de compilation. Il permet  d’exĂ©cuter des requĂŞtes SPARQL select et construct et de manipuler les rĂ©sultats. Les objets du langages sont les  graphes, les triplets et les termes RDF,  les solutions de requĂŞtes SPARQL et des listes de tels objets. Il offre des fonctions du second ordre: funcall, apply, map, reduce.

     
  • Decentralized Data Management for the Semantic Web
    Hala Skaf-Molli et Pascal Molli
    Thursday, March 29, 2018 – 10:30
    Room Aurigny
    Talk abstract: 

    The semantic web is an extension of the web where information has a precise meaning. Thousands of linked datasets are available on the web. Important problems concerning quality, deep web access and availability still unsolved. For data quality, we propose to transform the web of data into a read/write web of data. A data consumer will able to correct an error. Allowing consumers to write the semantic web poses the problem of data consistency. We define synchronization algorithms for RDF data model. To access to the deep web, we propose a mediator approach allowing to combine semantic data and deep web data. The problem is to improve the performance of queries in the presence of a large number of data sources. Finally, to ensure the availability, we propose a replication model for the web of data. The problem is to optimize federated SPARQL queries in the presence of replicas selected at queries execution time.

     In this talk, we will present our contribution concerning  the deep web access and data availability in the semantic web.
     
     
  • A metagenomics (and few other things) perspective on the “star” diatom Asterionella formosa
    Adrien Villain (IGS CNRS)
    Tuesday, March 27, 2018 – 10:30
    Room Aurigny
    Talk abstract: 

    Diatoms are unicellular microalgae often found in association with numerous bacterial partners. These interactions may be beneficial, neutral or detrimental, and may evolve over time depending on environmental conditions. Here I will describe how we used laboratory techniques, metagenomics and 16S barcoding to characterize the bacterial community of a non-model freshwater species, Asterionella formosa. Emphasis will be put on the technical challenges of metagenomics assembly, an assessment of the pros and cons of the methods we used, and our recent collaborative work on the prediction of metabolic complementarities within the community.

     
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  • A metagenomics (and few other things) perspective on the “star” diatom Asterionella formosa
    Adrien Villain (Information génomique et structurale, CNRS Marseille)
    Thursday, February 22, 2018 – 10:30
    Room Aurigny
    Talk abstract: 

    Diatoms are unicellular microalgae often found in association with numerous bacterial partners. These interactions may be beneficial, neutral or detrimental, and may evolve over time depending on environmental conditions. Here I will describe how we used laboratory techniques, metagenomics and 16S barcoding to characterize the bacterial community of a non-model freshwater species, Asterionella formosa. Emphasis will be put on the technical challenges of metagenomics assembly, an assessment of the pros and cons of the methods we used, and our recent collaborative work on the prediction of metabolic complementarities within the community.

     
  • Genome assembly and bioinformatics with haplotypes
    Bernardo Clavijo (Earlham Institute)
    Thursday, February 15, 2018 – 10:30
    Room Aurigny
    Talk abstract: 

    Producing and analysing de novo assemblies of complex organisms is now common across all life sciences. Still, these assemblies are mostly collapsed mosaics representing all haplotypes in single assembled regions. An excessive focus on contiguity has left precision and haplotype phasing as secondary concerns, despite advances in sequencing technologies that generate unprecedented amounts of information about haplotype composition.Here we will explore the possibilities and limitations of haplotype reconstruction on genome assembly, and the current trade-offs on assembly methods in different scenarios such as heterozygous and polyploid samples with short, long and linked reads. We will describe problems and solutions for the reconstruction and analysis of haplotypes in genome graphs. Finally, we will highlight the convergence of genetic and genomic evidence for haplotype studies and conclude with our vision of how the field could evolve in the near future. 

     
  • SĂ©minaire des CDD Symbiose 2018
    seminaireCDD
    Thursday, February 8, 2018 – 14:15 to 18:00
    Room Markov
    Talk abstract: 

    14h – 14h20 PrĂ©sentation des Ă©quipes 

     

    14h 20 – 16h PrĂ©sentations de quelques travaux dans Symbiose

     
    • Wesley Delage, “Le Benchmarking, de la bonne initiative aux dĂ©rives
    • Lucas Bourneuf, “Comment j’ai mangĂ© mes donnĂ©es”
    • Camille Marchet, “Retours sur une thèse chez GenScale”
    • JĂ©rĂ©my Gauthier,  “Et si on continuait Ă  faire de la recherche ?”
    • Joseph Kervellec et ChloĂ© Riou, prĂ©sentation des services dĂ©veloppĂ©s par Genouest
    16 h break sucré
     
    16h30 – 17 h PrĂ©sentation association & projet (Nicomaque,SEC, journal club…)
     
    17h – 18h Table ronde
    • Partage d’expĂ©rience, questions relatives au monde de la recherche, vie dans Symbiose

     

     

  • Exploring metabolic modulations using genome-scale network modelling and omics data in the context of toxicological studies: application for deciphering metabolic shifts occurring during the differentiation of the human hepatic cell line HepaRG
    Nathalie Poupin (INRA)
    Thursday, February 8, 2018 – 10:30
    Room Aurigny
    Talk abstract: 

    Many man-made chemicals present as contaminants in food and/or water are strongly suspected to induce adverse metabolic effects in Human. Liver is the key organ for xenobiotics biotransformation, and the use of metabolically competent cell lines is essential to explore the mechanisms underlying the metabolic effects of these substances. The hepatic cell line HepaRG, which is increasingly used in toxicity studies, has the particularity to differentiate from progenitor to mature hepatocyte-like cells. We combined multi-omics data and in silico methods in order to better characterize the metabolic capacities of this cell line and to explore the metabolic shifts occurring during this differentiation process. We integrated transcriptomic and metabolomic data in the context of the global human genome-scale metabolic network Recon2, which gathers the metabolic reactions the organism can perform and their associated genes, to compute a relevant sub-network, more specifically representing the functional hepatic metabolic network of HepaRG cells at each developmental stages: day 3 (progenitors) and day 30 (differentiated cells). We used a modified version of the iMAT algorithm developed by Shlomi et al. to identify, based on these data, the sub-networks of reactions specifically active in HepaRG cells at each developmental stage. For each stage, we identified several sub-networks of active reactions, having an equivalent adequacy to experimental data. We applied classification analysis methods to explore intra- and inter-stages variability among these sub-networks. We showed that, for each stage, the heterogeneity between sub-networks was mainly caused by the occurrence of several alternative reactions or the relative low contribution of transcriptomic data in some pathways. To better characterize the systemic metabolic capacities of the cells, we chose, contrary to most approaches, to consider the whole set of similarly adequate sub-networks, since it allows taking into account various metabolic alternatives. Through simulations and pathway enrichment analyses, we predicted that differentiated cells would globally be able to perform a larger number of liver-specific functions (e.g., urea production) and we identified several sets of reactions that were differently active between the two stages. These reactions mostly belong to pathways specific to hepatic activity (e.g., bile acid synthesis) but also to fatty acid synthesis and oxidation pathways. About 50% of the predicted modulated reactions were not evidenced from transcriptomic data and were « newly Â» inferred by the computational models. Globally, we showed that combining in silico methods with omics data enables to characterize global shifts in the developing hepatic metabolic network.

     

  • Mise en place de panels de rĂ©fĂ©rence sur la population française pour aider Ă  l’interprĂ©tation des donnĂ©es issues du sĂ©quençage nouvelle gĂ©nĂ©ration.
    Emmanuelle Genin (UMR 1078 Genetics, functional genomics and biotechnology )
    Thursday, February 1, 2018 – 10:30
    Room Minquiers
    Talk abstract: 

    Les nouvelles techniques de sĂ©quençage permettent aujourd’hui de caractĂ©riser l’ensemble des variations gĂ©nĂ©tiques prĂ©sentes sur tout le gĂ©nome ou sa partie codante (exome) d’un individu. On peut ainsi mettre en Ă©vidence de nouveaux variants gĂ©nĂ©tiques impliquĂ©s dans des maladies monogĂ©niques ou facteurs de risque de maladies complexes. Les mĂ©thodes d’analyse et les problĂ©matiques posĂ©es pour l’étude de ces deux types de maladies sont diffĂ©rentes mais dans les deux cas, le dĂ©fi majeur qui se pose est celui de l’interprĂ©tation de la fonctionnalitĂ© des variants dĂ©couverts. En effet, chaque exome humain contient environ 100 000 variations nuclĂ©otidiques dont certaines sont rares et non rĂ©pertoriĂ©es dans les bases de donnĂ©es. Utiliser cette information sur la frĂ©quence pour juger du caractère potentiellement dĂ©lĂ©tère de la variation pose cependant problème car les bases de donnĂ©es actuellement disponibles ne contiennent pas d’exomes provenant de nos rĂ©gions gĂ©ographiques. Or, toutes les Ă©tudes d’association pangĂ©nomiques rĂ©alisĂ©es ces dernières annĂ©es ont montrĂ© que des variations de frĂ©quences allĂ©liques existent entre pays en Europe et mĂŞme au sein d’un mĂŞme pays selon la rĂ©gion gĂ©ographique. Ces variations de frĂ©quences dĂ©tectables sur les variants gĂ©nĂ©tiques frĂ©quents et donc en gĂ©nĂ©ral plus anciens doivent exister et de manière encore plus importante pour les variants gĂ©nĂ©tiques rares apparus plus rĂ©cemment dans les populations et n’ayant donc pas eu le temps de se disperser dans l’espace. Disposer de bases de donnĂ©es de gĂ©nomes français semble donc ĂŞtre un prĂ©alable indispensable pour exploiter l’information gĂ©nĂ©tique apportĂ©e par le sĂ©quençage. C’est dans ce but que nous avons mis en place diffĂ©rents projets nationaux que nous prĂ©senterons dans cet exposĂ© en montrant ce qu’ils apportent par rapport aux bases de donnĂ©es internationales et dans le contexte de la mise en place du plan France MĂ©decine GĂ©nomique 2025 qui vise Ă  introduire le sĂ©quençage dans la pratique clinique. 

     

  • Probing virus-host interactions in complex microbial communities using DNA 3D contacts.
    Romain Koszul (Pasteur)
    Thursday, January 25, 2018 – 10:30
    Room Minquiers
    Talk abstract: 

     

     
  • Alternative strategies for diagnostic Epitranscriptomics to psychiatric applications Synthetic biology to build micromachines
    Alexandra Prieux, ALCEDIAG, SKILLCELL, Paris & Franck Molina, Sys2Diag, CNRS, ALCEDIAG, SKILLCELL Montpellier
    Thursday, January 11, 2018 – 10:30
    Room Aurigny
    Talk abstract: 

    Diagnostic may be understood in a broad sense as a mean to gain more insight into the world, including living and non-living elements. It thus includes medical diagnostic as well as the means of analysis and of understanding of our environment.Medical diagnostic tests in particular represent less than 5% of hospital cost and about 1.6 % of all health cost. Their results influence up to 60-70% medical decision. Despite this success, it remains many pathologies out of scope for medical diagnostic due to the lack of objective and relevant biomarkers or technological limitations.Crossing disciplines at Sys2diag, CNRS and two companies from ALCEN group (ALCEDIAG and SKILLCELL) developed alternative strategies for next generation diagnostic. The first example will describe new epitranscriptomic biomakers that allow to predict risk of psychiatric disorder, in particular depression and suicide. This approach is based on NGS technology and data analyses within clinical context. The second example, will show how using synthetic biology approaches we manage to design fully biological micromachines as robust diagnostic devices. All these works require tight relationships between various disciplines like biology, physic, computing, biostatisitcs.

     

     

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