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265 results on '"France Génomique"'

101. Integration of QTL, Transcriptome and Polymorphism Studies Reveals Candidate Genes for Water Stress Response in Tomato

Author: Isidore Diouf, Justine Gricourt, Sylvain Santoni, Elise Albert, Mathilde Causse, Frédérique Bitton, Renaud Duboscq, Génétique et Amélioration des Fruits et Légumes (GAFL), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Amélioration génétique et adaptation des plantes méditerranéennes et tropicales (UMR AGAP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Organisation et montée en puissance d'une Infrastructure Nationale de Génomique [En savoir plus]France-Génomique - ANR-10-INBS-09-01/10-INBS-0009Infrastructures - INBS - 2010, and ANR-13-ADAP-0013,AdapTom,Diversité et bases génétiques, génomiques et (éco)physiologiques de l'adaptation de la tomate à une limitation en eau et à d'autres stress environnementaux(2013)
Subjects: 0106 biological sciences, 0301 basic medicine, genotype x watering regime interaction, Candidate gene, lcsh:QH426-470, Population, Quantitative Trait Loci, Quantitative trait locus, Biology, 01 natural sciences, Polymorphism, Single Nucleotide, Article, Transcriptome, 03 medical and health sciences, Solanum lycopersicum, Osmotic Pressure, Genotype, Genetics, genotype × watering regime interaction, Cultivar, education, Gene, Genetics (clinical), Plant Proteins, water deficit, 2. Zero hunger, education.field_of_study, food and beverages, RNA sequencing, Phenotype, Droughts, Plant Leaves, lcsh:Genetics, [SDV.BV.AP]Life Sciences [q-bio]/Vegetal Biology/Plant breeding, 030104 developmental biology, Fruit, transcriptome, 010606 plant biology & botany
Abstract: International audience; Water deficit (WD) leads to significant phenotypic changes in crops resulting from complex stress regulation mechanisms involving responses at the physiological, biochemical and molecular levels. Tomato growth and fruit quality have been shown to be significantly affected by WD stress. Understanding the molecular mechanism underlying response to WD is crucial to develop tomato cultivars with relatively high performance under low watering conditions. Transcriptome response to WD was investigated through the RNA sequencing of fruit and leaves in eight accessions grown under two irrigation conditions, in order to get insight into the complex genetic regulation of WD response in tomato. Significant differences in genotype WD response were first observed at the phenotypic level for fruit composition and plant development traits. At the transcriptome level, a total of 14,065 differentially expressed genes (DEGs) in response to WD were detected, among which 7393 (53%) and 11,059 (79%) were genotype- and organ-specific, respectively. Water deficit induced transcriptome variations much stronger in leaves than in fruit. A significant effect of the genetic background on expression variation was observed compared to the WD effect, along with the presence of a set of genes showing a significant genotype x watering regime interaction. Integrating the DEGs with previously identified WD response quantitative trait loci (QTLs) mapped in a multi-parental population derived from the crossing of the eight genotypes narrowed the candidate gene lists to within the confidence intervals surrounding the QTLs. The results present valuable resources for further study to decipher the genetic determinants of tomato response to WD.
Published: 2020
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102. Introductions and early spread of SARS-CoV-2 in France, 24 January to 23 March 2020

Author: Mélanie Albert, Fawzi Derrar, Sylvie Behillil, Flora Donati, Sylvie van der Werf, Marion Barbet, Andreea Alexandru, Etienne Simon-Loriere, Fabiana Gámbaro, Angela Brisebarre, Maud Vanpeene, Artem Baidaliuk, Meline Bizard, Vincent Enouf, Génomique évolutive des virus à ARN - Evolutionary genomics of RNA viruses, Institut Pasteur [Paris] (IP), Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR - laboratoire coordonnateur), Génétique Moléculaire des Virus à ARN - Molecular Genetics of RNA Viruses (GMV-ARN (UMR_3569 / U-Pasteur_2)), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Plateforme de Microbiologie Mutualisée (PIBnet) - Mutualized Platform for Microbiology (P2M), National Influenza Center, Viral Respiratory Laboratory [Alger], This study has received funding from Institut Pasteur, CNRS, Université de Paris, Santé publique France, the French Government's Investissement d'Avenir programme, Laboratoire d'Excellence 'Integrative Biology of Emerging Infectious Diseases' (grant n°ANR-10-LABX-62-IBEID), REACTing (Research & Action Emerging Infectious Diseases), France Génomique (ANR-10-INBS-09-09), IBISA, and the RECOVER project funded by the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 101003589. ESL acknowledges funding from the INCEPTION programme (Investissements d’Avenir grant ANR-16-CONV-0005)., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), European Project: 101003589, H2020-SC1-PHE-CORONAVIRUS-2020,RECOVER(2020), Institut Pasteur [Paris], Centre National de Référence des virus des infections respiratoires (dont la grippe) - National Reference Center Virus Influenzae [Paris] (CNR), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)
Subjects: 0301 basic medicine, MESH: Coronavirus Infections, Epidemiology, [SDV]Life Sciences [q-bio], phylogeny, Disease Outbreaks, 0302 clinical medicine, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH: Coronavirus, outbreak surveillance, MESH: COVID-19, 030212 general & internal medicine, MESH: Disease Outbreaks, MESH: Phylogeny, Clade, virus genomics, Phylogenetic tree, biology, Reverse Transcriptase Polymerase Chain Reaction, Transmission (medicine), 3. Good health, Geography, MESH: RNA, Viral, MESH: Sentinel Surveillance, RNA, Viral, MESH: Betacoronavirus, France, MESH: Genome, Viral, Coronavirus Infections, Sequence Analysis, Rapid Communication, MESH: Pandemics, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Pneumonia, Viral, Zoology, Genome, Viral, Betacoronavirus, Viral Proteins, MESH: Sequence Analysis, 03 medical and health sciences, Virology, Humans, MESH: SARS-CoV-2, Pandemics, MESH: Humans, SARS-CoV-2, Public Health, Environmental and Occupational Health, COVID-19, biology.organism_classification, MESH: Viral Proteins, Coronavirus, MESH: France, 030104 developmental biology, MESH: Pneumonia, Viral, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Sentinel Surveillance
Abstract: International audience; Following SARS-CoV-2 emergence in China, a specific surveillance was implemented in France. Phylogenetic analysis of sequences retrieved through this surveillance suggests that detected initial introductions, involving non-clade G viruses, did not seed local transmission. Nevertheless, identification of clade G variants subsequently circulating in the country, with the earliest from a patient who neither travelled to risk areas nor had contact with travellers, suggests that SARS-CoV-2 might have been present before the first recorded local cases.
Published: 2020
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103. Leishmania amazonensis Subverts the Transcription Factor Landscape in Dendritic Cells to Avoid Inflammasome Activation and Stall Maturation

Author: Hervé Lecoeur, Thibault Rosazza, Kossiwa Kokou, Hugo Varet, Jean-Yves Coppée, Arezou Lari, Pierre-Henri Commère, Robert Weil, Guangxun Meng, Genevieve Milon, Gerald F. Späth, Eric Prina, Key Laboratory of Molecular Virology and Immunology [Shanghai, China], Institut Pasteur de Shanghai, Académie des Sciences de Chine - Chinese Academy of Sciences (IPS-CAS), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Parasitologie moléculaire et Signalisation / Molecular Parasitology and Signaling, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Pasteur International Mixed Unit 'Inflammation and Leishmania infection' (IMU-InflaLeish), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Innate Immunity [China], Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut Pasteur de Shanghai, Académie des Sciences de Chine - Chinese Academy of Sciences (IPS-CAS), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Leishmania Lab [Corée du sud], Institut Pasteur Korea - Institut Pasteur de Corée, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut Pasteur Korea - Institut Pasteur de Corée, Réseau International des Instituts Pasteur (RIIP), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Transcriptome et Epigénome (PF2), Institut Pasteur [Paris], Institut Pasteur d'Iran, Cytométrie (Plate-forme), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Immunophysiologie et Parasitisme, This project was supported by a fund of the Institut Pasteur International Direction to the Pasteur International Unit Inflammation and Leishmania infection and by the Fonds Dèdié Sanofi-Aventis/Ministère de la Recherche et de l'Enseignement Supérieur and Combattre les Maladies Parasitaires. The Institut Pasteur Biomics Platform was supported by France Génomique (ANR-10-INBS-09-09) and IBISA., ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), Varet, Hugo, Organisation et montée en puissance d'une Infrastructure Nationale de Génomique - - France-Génomique2010 - ANR-10-INBS-0009 - INBS - VALID, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Innate Immunity [China], Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), and Centre d'Immunologie et des Maladies Infectieuses (CIMI)
Subjects: 0301 basic medicine, lcsh:Immunologic diseases. Allergy, dendritic cell, [SDV]Life Sciences [q-bio], Antigen presentation, Immunology, Biology, NF-κB, 03 medical and health sciences, 0302 clinical medicine, Immune system, NLRP3, Gene expression, MHC class I, medicine, Immunology and Allergy, Amastigote, cell sorting, transcription factor, Original Research, Inflammasome, Dendritic cell, Phenotype, amastigote, Cell biology, [SDV] Life Sciences [q-bio], 030104 developmental biology, biology.protein, lcsh:RC581-607, transcriptome, 030215 immunology, medicine.drug, Leishmania amazonensis
Abstract: International audience; Leishmania parasites are the causative agents of human leishmaniases. They infect professional phagocytes of their mammalian hosts, including dendritic cells (DCs) that are essential for the initiation of adaptive immune responses. These immune functions strictly depend on the DC's capacity to differentiate from immature, antigen-capturing cells to mature, antigen-presenting cells-a process accompanied by profound changes in cellular phenotype and expression profile. Only little is known on how intracellular Leishmania affects this important process and DC transcriptional regulation. Here, we investigate these important open questions analyzing phenotypic, cytokine profile and transcriptomic changes in murine, immature bone marrow-derived DCs (iBMDCs) infected with antibody-opsonized and non-opsonized Leishmania amazonensis (L.am) amastigotes. DCs infected by non-opsonized amastigotes remained phenotypically immature whereas those infected by opsonized parasites displayed a semi-mature phenotype. The low frequency of infected DCs in culture led us to use DsRed2-transgenic parasites allowing for the enrichment of infected BMDCs by FACS. Sorted infected DCs were then subjected to transcriptomic analyses using Affymetrix GeneChip technology. Independent of parasite opsonization, Leishmania infection induced expression of genes related to key DC processes involved in MHC Class I-restricted antigen presentation and alternative NF-κB activation. DCs infected by non-opsonized parasites maintained an immature phenotype and showed a small but significant down-regulation of gene expression related to pro-inflammatory TLR signaling, the canonical NF-kB pathway and the NLRP3 inflammasome. This transcriptomic profile was further enhanced in Lecoeur et al. DC Subversion by Leishmania Amazonensis DCs infected with opsonized parasites that displayed a semi-mature phenotype despite absence of inflammasome activation. This paradoxical DC phenotype represents a Leishmania-specific signature, which to our knowledge has not been observed with other opsonized infectious agents. In conclusion, systems-analyses of our transcriptomics data uncovered important and previously unappreciated changes in the DC transcription factor landscape, thus revealing a novel Leishmania immune subversion strategy directly acting on transcriptional control of gene expression. Our data raise important questions on the dynamic and reciprocal interplay between transacting and epigenetic regulators in establishing permissive conditions for intracellular Leishmania infection and polarization of the immune response.
Published: 2020
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104. Intracellular Staphylococcus aureus persisters upon antibiotic exposure

Author: Jean-Yves Coppée, Tanel Tenson, Rachel Legendre, Frédéric Peyrusson, Christiane Wolz, Odile Sismeiro, Hugo Varet, Tiep Khac Nguyen, Françoise Van Bambeke, Pharmacologie Cellulaire et Moléculaire [Brussels], Louvain Drug Research Institute [Bruxelles, Belgique] (LDRI), Université Catholique de Louvain = Catholic University of Louvain (UCL)-Université Catholique de Louvain = Catholic University of Louvain (UCL), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Transcriptome et Epigénome (PF2), Institut Pasteur [Paris] (IP), University of Tübingen, Institute of Technology [Tartu, Estonia], University of Tartu, This work was supported by the Belgian Fonds de la Recherche Scientifique (FNRS-FRS) (grants T.0189.16 and J.0018.17) and the Interuniversity Attraction Poles Program initiated by the Belgian Science Policy Office (program IAP P7/28). F.P. is recipient of a PhD fellowship from the Université catholique de Louvain, T.K.N. was successively junior research fellow from the Fonds de coopération of the Université catholique de Louvain and from the Académie de Recherche et d’Enseignement Supérieur (ARES), F.V.B. is Research Director of the Belgian FNRS-FRS, C.W. is funded by the Deutsche Forschungsgemeinschaft (SFB156), T.T. is funded by the Estonian Research Council (PRG335). The Transcriptome and Epigenome Platform is a member of the France Génomique consortium (ANR10‐NBS‐09‐08)., ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris], and UCL - SSS/LDRI - Louvain Drug Research Institute
Subjects: 0301 basic medicine, THP-1 Cells, Stringent response, [SDV]Life Sciences [q-bio], Antibiotics, Cellular microbiology, General Physics and Astronomy, Drug resistance, medicine.disease_cause, Mice, Drug Resistance, Multiple, Bacterial, lcsh:Science, Cells, Cultured, Microscopy, Confocal, Multidisciplinary, Anti-Bacterial Agents, 3. Good health, Staphylococcus aureus, Antibacterial drug resistance, MCF-7 Cells, Pathogens, Multidrug tolerance, medicine.drug_class, Science, 030106 microbiology, Microbial Sensitivity Tests, Biology, Article, General Biochemistry, Genetics and Molecular Biology, Cell Line, Bacterial genetics, Microbiology, 03 medical and health sciences, Cell Line, Tumor, medicine, Animals, Humans, Microbial Viability, Gene Expression Profiling, Macrophages, Gene Expression Regulation, Bacterial, General Chemistry, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 030104 developmental biology, A549 Cells, lcsh:Q, Energy Metabolism, Bacteria
Abstract: Bacterial persister cells are phenotypic variants that exhibit a transient non-growing state and antibiotic tolerance. Here, we provide in vitro evidence of Staphylococcus aureus persisters within infected host cells. We show that the bacteria surviving antibiotic treatment within host cells are persisters, displaying biphasic killing and reaching a uniformly non-responsive, non-dividing state when followed at the single-cell level. This phenotype is stable but reversible upon antibiotic removal. Intracellular S. aureus persisters remain metabolically active but display an altered transcriptomic profile consistent with activation of stress responses, including the stringent response as well as cell wall stress, SOS and heat shock responses. These changes are associated with multidrug tolerance after exposure to a single antibiotic. We hypothesize that intracellular S. aureus persisters may constitute a reservoir for relapsing infection and could contribute to therapeutic failures., Bacterial persister cells exhibit a transient non-growing state and antibiotic tolerance. Here, Peyrusson et al. provide evidence of metabolically active Staphylococcus aureus persisters within infected host cells exposed to antibiotics and analyse transcriptomic alterations associated with persistence.
Published: 2020
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105. Chromosomal resolution reveals symbiotic virus colonization of parasitic wasp genomes

Author: Gauthier, Jérémy, BOULAIN, Hélène, van Vugt, Joke J.F.A., Baudry, Lyam, Persyn, Emma, Aury, Jean-Marc, Noel, Benjamin, Bretaudeau, Anthony, Legeai, Fabrice, Warris, Sven, Chebbi, Mohamed Amine, Dubreuil, Géraldine, Duvic, Bernard, Kremer, Natacha, Gayral, Philippe, Musset, Karine, Josse, Thibaut, Bigot, Diane, Bressac, Christophe, Moreau, Sébastien, Periquet, Georges, Harry, Myriam, Montagne, Nicolas, Boulogne, Isabelle, Sabeti-Azad, Mahnaz, Maïbèche, Martine, Chertemps, Thomas, Hilliou, Frédérique, Siaussat, David, Amselem, Joëlle, Luyten, Isabelle, Capdevielle-Dulac, Claire, Labadie, Karine, Merlin, Bruna Laís, Barbe, Valérie, de Boer, Jetske, Marbouty, Martial, Cônsoli, Fernando Luis, Vet, Louise E.M., Cônsoli, Fernando, Dupas, Stéphane, Hua Van, Aurélie, Le Goff, Gaëlle, Bézier, Annie, Jacquin-Joly, Emmanuelle, Whitfield, James, Vet, Louise, Smid, Hans, Kaiser-Arnault, Laure, Koszul, Romain, Huguet, Elisabeth, Herniou, Elisabeth, Drezen, Jean-Michel, Institut de recherche sur la biologie de l'insecte UMR7261 (IRBI), Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Régulation spatiale des Génomes - Spatial Regulation of Genomes, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Collège Doctoral, Sorbonne Université (SU), Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Institut de Génétique, Environnement et Protection des Plantes (IGEPP), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-INSTITUT AGRO Agrocampus Ouest, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Diversité, Génomes & Interactions Microorganismes - Insectes [Montpellier] (DGIMI), Université de Montpellier (UM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Evolution, génomes, comportement et écologie (EGCE), Institut de Recherche pour le Développement (IRD)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut d'écologie et des sciences de l'environnement de Paris (iEES Paris ), Institut de Recherche pour le Développement (IRD)-Sorbonne Université (SU)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Sophia Agrobiotech (ISA), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Côte d'Azur (UCA), Unité de Recherche Génomique Info (URGI), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), France Génomique (UMS CNRS 3628 - INRAE 1396 - Inserm 026), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Nederlands Instituut Voor Ecologie - NIOO (NETHERLANDS), Université de Tours-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-AGROCAMPUS OUEST, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-INSTITUT AGRO Agrocampus Ouest, Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Bretagne Sud (UBS)-École normale supérieure - Rennes (ENS Rennes)-Institut National de Recherche en Informatique et en Automatique (Inria)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Collège doctoral [Sorbonne universités], Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Institut National de la Recherche Agronomique (INRA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-AGROCAMPUS OUEST, Université de Bretagne Sud (UBS)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National de Recherche en Informatique et en Automatique (Inria)-École normale supérieure - Rennes (ENS Rennes)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-CentraleSupélec-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut de Recherche pour le Développement (IRD)-Sorbonne Université (SU)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Nice Sophia Antipolis (... - 2019) (UNS), and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: 0106 biological sciences, 0303 health sciences, food.ingredient, Host (biology), [SDV]Life Sciences [q-bio], fungi, Duurzame gewasbescherming, Parasitism, Biology, biology.organism_classification, 010603 evolutionary biology, 01 natural sciences, Genome, Virus, Wespen, Parasitoid wasp, Parasitoid, 03 medical and health sciences, food, Evolutionary biology, Bracovirus, Gene, 030304 developmental biology
Abstract: Most endogenous viruses, an important proportion of eukaryote genomes, are doomed to slowly decay. Little is known, however, on how they evolve when they confer a benefit to their host. Bracoviruses are essential for the parasitism success of parasitoid wasps, whose genomes they integrated ~103 million years ago. Here we show, from the assembly of a parasitoid wasp genome, for the first time at a chromosomal scale, that symbiotic bracovirus genes spread to and colonized all the chromosomes. Moreover, large viral clusters are stably maintained suggesting strong evolutionary constraints. Genomic comparison with another wasps revealed that this organization was already established ~53 mya. Transcriptomic analyses highlight temporal synchronization of viral gene expression, leading to particle production. Immune genes are not induced, however, indicating the virus is not perceived as foreign by the wasp. This recognition suggests that no conflicts remain between symbiotic partners when benefits to them converge.
Published: 2020
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106. Insights into amebiasis using a human 3D-intestinal model

Author: Nancy Guillén, Mariette Matondo, Julien Fernandes, Jean-Yves Coppée, Rachel Legendre, Silvia Castellanos-Castro, Hugo Varet, David Hardy, Odile Sismeiro, Arturo Aguilar-Rojas, Quentin Giai Gianetto, Jean-Christophe Olivo-Marin, Analyse d'images biologiques - Biological Image Analysis (BIA), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Instituto Mexicano del Seguro Social [Mexico City, Mexico] (IMSS), Universidad Autónoma de la Ciudad de México (UACM), Spectrométrie de Masse pour la Biologie – Mass Spectrometry for Biology (UTechS MSBio), Institut Pasteur [Paris]-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Transcriptome et Epigénome (PF2), Institut Pasteur [Paris], Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, BioImagerie Photonique – Photonic BioImaging (UTechS PBI), Neuropathologie expérimentale / Experimental neuropathology, Institut Pasteur [Paris]-Université de Paris (UP), The project has received funding from the European ERA‐NET Infect‐ERA program AMOEBAC (French National Agency for Research [ANR] grants ANR‐14‐IFEC‐0001‐01 and ANR‐14‐IFEC‐0001‐02). Biomics Platform (Institute Pasteur) is supported by France Génomique (ANR‐10‐INBS‐09‐09) and IBISA. AAR is a recipient of Research Career Development Awards from Fundación‐IMSS, México. SCC received a postdoctoral fellowship with number 173697 from the program S190‐Conacyt, 2017, Mexico., ANR-14-IFEC-0001,AMOEBAC,Entamoeba histolytica-bacterium interaction and the role of this interaction in intestinal pathogenesis.(2014), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), and Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité)
Subjects: Models, Anatomic, Immunology, Virulence, Inflammation, Microbiology, Host-Parasite Interactions, Adherens junction, 03 medical and health sciences, Entamoeba histolytica, Immune system, Virology, medicine, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Fibroblast, 030304 developmental biology, 0303 health sciences, Microscopy, Confocal, biology, 030306 microbiology, Amebiasis, biology.organism_classification, In vitro, 3. Good health, Intestines, secretome, medicine.anatomical_structure, 3D-intestinal model, Infectious disease (medical specialty), inflammation, Dysentery, Amebic, medicine.symptom, transcriptome
Abstract: International audience; Entamoeba histolytica is the causative agent of amebiasis, an infectious disease targeting the intestine and the liver in humans. Two types of intestinal infection are caused by this parasite: silent infection, which occurs in the majority of cases, and invasive disease, which affects 10% of infected persons. To understand the intestinal pathogenic process, several in vitro models, such as cell cultures, human tissue explants or human intestine xenografts in mice, have been employed. Nevertheless, our knowledge on the early steps of amebic intestinal infection and the molecules involved during human-parasite interaction is scarce, in part due to limitations in the experimental settings. In the present work, we took advantage of tissue engineering approaches to build a three-dimensional (3D)-intestinal model that is able to replicate the general characteristics of the human colon. This system consists of an epithelial layer that develops tight and adherens junctions, a mucus layer and a lamina propria-like compartment made up of collagen containing macrophages and fibroblast. By means of microscopy imaging, omics assays and the evaluation of immune responses, we show a very dynamic interaction between E. histolytica and the 3D-intestinal model. Our data highlight the importance of several virulence markers occurring in patients or in experimental models, but they also demonstrate the involvement of under described molecules and regulatory factors in the amoebic invasive process.
Published: 2020
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107. Impact of the gut microbiota on the m 6 A epitranscriptome of mouse cecum and liver

Author: Pascale Cossart, Marie-Agnès Dillies, Sabrina Jabs, Amine Ghozlane, Quentin Giai Gianetto, Vincent Guérineau, Christophe Bécavin, David Touboul, Alessandro Pagliuso, Giulia Spanò, Mariette Matondo, Marie-Anne Nahori, Thibault Chaze, Anne Biton, Interactions Bactéries-Cellules (UIBC), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie des Substances Naturelles (ICSN), Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Spectrométrie de Masse pour la Biologie – Mass Spectrometry for Biology (UTechS MSBio), Institut Pasteur [Paris] (IP)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), We thank Marion Bérard and the Gnotobiology platform of the Institut Pasteur for support in conducting gnotobiology experiments, the Pasteur Biomics platforms for Transcriptomics and Epigenetics and Metagenomics for providing RNA sequencing and 16S rRNA sequencing services, Cédric Fund, Biomics Platform, C2RT, Institut Pasteur, Paris, France, supported by France Génomique (ANR-10-INBS-09-09) and IBISA, Carla Saleh and Olivier Dussurget for helpful discussions, Hugo Varet (Institut Pasteur Bionformatics and Statistics Hub) for advice concerning statistical analysis, Stevenn Volant for help with analysis of 16S sequencing data. This work was supported by grants to P.C.: European Research Council (ERC) Advanced Grant BacCellEpi (670823), ANR Investissement d’Avenir Programme (10-LABX-62-IBEID), ERANET-Infect-ERA PROANTILIS (ANR-13-IFEC-0004-02) and the Fondation Le Roch-Les Mousquetaires. S.J. was supported by a Danone Research fellowship and European Research Council (ERC) Advanced Grant BacCellEpi (670823)., ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-13-IFEC-0004,PROANTILIS,Subversive pro- and anti-inflammation trade-offs promote infection by Listeria monocytogenes(2013), European Project: 670823,H2020,ERC-2014-ADG,BacCellEpi(2015), Nahori, marie-anne, Organisation et montée en puissance d'une Infrastructure Nationale de Génomique - - France-Génomique2010 - ANR-10-INBS-0009 - INBS - VALID, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, ERA-NET Infect-ERA - Subversive pro- and anti-inflammation trade-offs promote infection by Listeria monocytogenes - - PROANTILIS2013 - ANR-13-IFEC-0004 - IFEC - VALID, Bacterial, cellular and epigenetic factors that control enteropathogenicity - BacCellEpi - - H20202015-10-01 - 2018-09-30 - 670823 - VALID, Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris]-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Adenosine, Methyltransferase, Science, [SDV]Life Sciences [q-bio], General Physics and Astronomy, Biology, Gut flora, Methylation, digestive system, Article, General Biochemistry, Genetics and Molecular Biology, Microbiology, Transcriptome, Mice, 03 medical and health sciences, Cecum, 0302 clinical medicine, fluids and secretions, Gene expression, medicine, Animals, RNA, Messenger, lcsh:Science, Multidisciplinary, Bacteria, Methyltransferases, General Chemistry, biology.organism_classification, Commensalism, Gastrointestinal Microbiome, Mice, Inbred C57BL, [SDV] Life Sciences [q-bio], stomatognathic diseases, 030104 developmental biology, medicine.anatomical_structure, Liver, Female, lcsh:Q, Microbiome, 030217 neurology & neurosurgery, Akkermansia muciniphila
Abstract: The intestinal microbiota modulates host physiology and gene expression via mechanisms that are not fully understood. Here we examine whether host epitranscriptomic marks are affected by the gut microbiota. We use methylated RNA-immunoprecipitation and sequencing (MeRIP-seq) to identify N6-methyladenosine (m6A) modifications in mRNA of mice carrying conventional, modified, or no microbiota. We find that variations in the gut microbiota correlate with m6A modifications in the cecum, and to a lesser extent in the liver, affecting pathways related to metabolism, inflammation and antimicrobial responses. We analyze expression levels of several known writer and eraser enzymes, and find that the methyltransferase Mettl16 is downregulated in absence of a microbiota, and one of its target mRNAs, encoding S-adenosylmethionine synthase Mat2a, is less methylated. We furthermore show that Akkermansia muciniphila and Lactobacillus plantarum affect specific m6A modifications in mono-associated mice. Our results highlight epitranscriptomic modifications as an additional level of interaction between commensal bacteria and their host., The intestinal microbiota modulates host physiology and gene expression via unclear mechanisms. Here, Jabs et al. show that variations in the gut microbiota correlate with N6-methyladenosine modifications of host mRNAs in the cecum and liver of mice.
Published: 2020
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108. Experimental evolution links post-transcriptional regulation to Leishmania fitness gain

Author: Laura Piel, K. Shanmugha Rajan, Giovanni Bussotti, Hugo Varet, Rachel Legendre, Caroline Proux, Thibaut Douché, Quentin Giai-Gianetto, Thibault Chaze, Thomas Cokelaer, Barbora Vojtkova, Nadav Gordon-Bar, Tirza Doniger, Smadar Cohen-Chalamish, Praveenkumar Rengaraj, Céline Besse, Anne Boland, Jovana Sadlova, Jean-François Deleuze, Mariette Matondo, Ron Unger, Petr Volf, Shulamit Michaeli, Pascale Pescher, Gerald F. Späth, Parasitologie moléculaire et Signalisation / Molecular Parasitology and Signaling, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), The Everard and Mina Goodman Faculty of Life Sciences, Bar-Ilan University [Israël], Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Biomics (plateforme technologique), Plateforme de Protéomique / Proteomics platform, Université Paris Cité (UPCité)-Spectrométrie de Masse pour la Biologie – Mass Spectrometry for Biology (UTechS MSBio), Institut Pasteur [Paris] (IP)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Institut Pasteur [Paris] (IP)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Charles University [Prague] (CU), The Mina and Everard Goodman Faculty of Life Sciences, Centre National de Recherche en Génomique Humaine (CNRGH), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), This work was supported by the Fondation de la Recherche Médicale contract FDT201805005619 (LP), the Agence Nationale pour la Recherche Labex ‘French Alliance for Parasitology and Health Care’ contract ANR-11-LABX-0024 (GFS, LP, PP, GB) and Labex ‘Integrative Biology of Emerging Infectious Diseases’ contract ANR-10-LABX-62-IBEID, the Campus France Franco-Israeli Programme Hubert Curien Maimonide 2018 (GFS and SM), the France Génomique National infrastructure, funded as part of the « Investissements d’Avenir » program managed by the Agence Nationale pour la Recherche contract ANR-10-INBS-09 (HV, RL, CP), the EU H2020 project LeiSHield-MATI - REP-778298-1 (GS), and the ERD Funds, project CePaViP (CZ.02.1.01/0.0/0.0/ 16_019/0000759) (BV, JS, PV)., We thank the CEA-CNRGH for its contribution to the sequencing costs and all the CEA-CNRGH staff who performed sample preparation and sequencing for their excellent technical assistance, ANR-11-LABX-0024,ParaFrap,Alliance française contre les maladies parasitaires(2011), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), and European Project: 778298,H2020,H2020-MSCA-RISE-2017,LeiSHield-MATI(2018)
Subjects: Proteomics, Gene Expression Regulation, [SDV]Life Sciences [q-bio], Virology, Immunology, Genetics, Humans, Leishmaniasis, Visceral, Parasitology, Molecular Biology, Microbiology, Genomic Instability, Leishmania donovani
Abstract: The protozoan parasite Leishmania donovani causes fatal human visceral leishmaniasis in absence of treatment. Genome instability has been recognized as a driver in Leishmania fitness gain in response to environmental change or chemotherapy. How genome instability generates beneficial phenotypes despite potential deleterious gene dosage effects is unknown. Here we address this important open question applying experimental evolution and integrative systems approaches on parasites adapting to in vitro culture. Phenotypic analyses of parasites from early and late stages of culture adaptation revealed an important fitness tradeoff, with selection for accelerated growth in promastigote culture (fitness gain) impairing infectivity (fitness costs). Comparative genomics, transcriptomics and proteomics analyses revealed a complex regulatory network associated with parasite fitness gain, with genome instability causing highly reproducible, gene dosage-independent and -dependent changes. Reduction of flagellar transcripts and increase in coding and non-coding RNAs implicated in ribosomal biogenesis and protein translation were not correlated to dosage changes of the corresponding genes, revealing a gene dosage-independent, post-transcriptional mechanism of regulation. In contrast, abundance of gene products implicated in post-transcriptional regulation itself correlated to corresponding gene dosage changes. Thus, RNA abundance during parasite adaptation is controled by direct and indirect gene dosage changes. We correlated differential expression of small nucleolar RNAs (snoRNAs) with changes in rRNA modification, providing first evidence that Leishmania fitness gain in culture may be controlled by post-transcriptional and epitranscriptomic regulation. Our findings propose a novel model for Leishmania fitness gain in culture, where differential regulation of mRNA stability and the generation of modified ribosomes may potentially filter deleterious from beneficial gene dosage effects and provide proteomic robustness to genetically heterogenous, adapting parasite populations. This model challenges the current, genome-centric approach to Leishmania epidemiology and identifies the Leishmania transcriptome and non-coding small RNome as potential novel sources for the discovery of biomarkers that may be associated with parasite phenotypic adaptation in clinical settings.
Published: 2022
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109. Crosstalk between BPA and FXRα Signaling Pathways Lead to Alterations of Undifferentiated Germ Cell Homeostasis and Male Fertility Disorders

Author: Lauriane Sèdes, Jean-Paul Saru, Bernard Jégou, Christelle Damon-Soubeyrand, Françoise Caira, Laura Thirouard, Emmanuelle Martinot, Séverine Mazaud-Guittot, Claude Beaudoin, Betty Rouaisnel, David H. Volle, Hélène Holota, Christèle Desdoits-Lethimonier, Laurianne Lesné, Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), École des Hautes Études en Santé Publique [EHESP] (EHESP), This study was conducted with the assistance of the 'Anipath' Platform (GReD). We thank Sandrine Plantade, Khireddine Ouchen, and Philippe Mazuel for animal facilities. The research team headed by D.H.V. is funded by Inserm, CNRS, Clermont Université, Nouveau Chercheur Auvergne (no. R12087CC to D.H.V.), and Plan Cancer – Cancer-Environnement 2014–2019 (C14012CS). D.H.V.’s team received support from the French government IDEX-ISITE initiative16-IDEX-0001 (CAP 20-25). Sequencing was performed by the IGBMC Microarray and Sequencing platform, a member of the 'France Génomique' consortium (ANR-10-INBS-0009)., ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), Chard-Hutchinson, Xavier, Organisation et montée en puissance d'une Infrastructure Nationale de Génomique - - France-Génomique2010 - ANR-10-INBS-0009 - INBS - VALID, Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Université d'Angers (UA)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: Male, 0301 basic medicine, Bisphenol-A, Receptors, Cytoplasmic and Nuclear, Biochemistry, Mice, 0302 clinical medicine, Testis, Homeostasis, lcsh:QH301-705.5, lcsh:R5-920, education.field_of_study, [SDV.TOX.ECO] Life Sciences [q-bio]/Toxicology/Ecotoxicology, 030219 obstetrics & reproductive medicine, Cell Differentiation, Middle Aged, Cell biology, Crosstalk (biology), medicine.anatomical_structure, [SDV.TOX.ECO]Life Sciences [q-bio]/Toxicology/Ecotoxicology, Signal transduction, lcsh:Medicine (General), Germ cell, hormones, hormone substitutes, and hormone antagonists, Signal Transduction, Adult, endocrine system, Population, Stigmasterol, FXRα, Biology, Article, 03 medical and health sciences, Fetus, Phenols, Downregulation and upregulation, Genetics, medicine, Animals, Humans, [SDV.EE.SANT] Life Sciences [q-bio]/Ecology, environment/Health, Endocrine system, Benzhydryl Compounds, education, Infertility, Male, [SDV.BDLR] Life Sciences [q-bio]/Reproductive Biology, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, Sertoli Cells, urogenital system, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, Cell Biology, Germ Cells, Fertility, 030104 developmental biology, lcsh:Biology (General), Animals, Newborn, Farnesoid X receptor, Developmental Biology
Abstract: Summary Several studies have reported an association between the farnesoid X receptor alpha (FXRα) and estrogenic signaling pathways. Fxrα could thus be involved in the reprotoxic effects of endocrine disruptors such as bisphenol-A (BPA). To test this hypothesis, mice were exposed to BPA and/or stigmasterol (S), an FXRα antagonist. Following the exposure to both molecules, wild-type animals showed impaired fertility and lower sperm cell production associated with the alteration of the establishment and maintenance of the undifferentiated germ cell pool. The crosstalk between BPA and FXRα is further supported by the lower impact of BPA in mice genetically ablated for Fxrα and the fact that BPA counteracted the effects of FXRα agonists. These effects might result from the downregulation of Fxrα expression following BPA exposure. BPA and S act additively in human testis. Our data demonstrate that FXRα activity modulates the impact of BPA on male gonads and on undifferentiated germ cell population., Highlights • BPA and S exposures synergistically induce male fertility disorders • BPA regulates Fxr expression • BPA and S act additively in human testis, In this article, Dr Volle and colleagues show that Fxrα participate in the reprotoxic effects of endocrine disruptors such as bisphenol-A (BPA). The present study shows that modulation of FXRa signaling pathway by the FXRα antagonist, namely stigmasterol, acts additively with BPA, leading to impaired fertility and lower sperm cell production associated with the alteration of the establishment and maintenance of the undifferentiated germ cell pool. In addition these additive effects were also observed in human testis.
Published: 2018
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110. Plasmid-mediated doxycycline resistance in a Yersinia pestis strain isolated from a rat

Author: Elisabeth Carniel, Christiane Bouchier, Minoarisoa Rajerison, Nicolas Cabanel, Yersinia, Institut Pasteur [Paris], Génomique (Plate-Forme) - Genomics Platform, Unité Peste - Plague Unit [Antananarivo, Madagascar], Institut Pasteur de Madagascar, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), This work was supported and funded in part by GlaxoSmithKline and the Defense Threat Reduction Agency [agreement no. HDTRA1-07-9-0002] for IP2180H phenotypic characterisation, and by the ‘France Génomique’ consortium (ANR10-INBS-09-08) for pIP1203 sequencing., Cyril Savin is thanked for his involvement in the assembly of the pIP2180H sequence, and Magali Tichit and Laurence Ma are thanked for their technical help in pIP1203 sequencing., ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), and Institut Pasteur [Paris] (IP)
Subjects: DNA, Bacterial, 0301 basic medicine, Microbiology (medical), MESH: Rats, Yersinia pestis, 030106 microbiology, MESH: Yersinia pestis, Drug resistance, MESH: Streptomycin, MESH: Plague, Microbiology, MESH: Madagascar, 03 medical and health sciences, Plasmid, Antibiotic resistance, Disk Diffusion Antimicrobial Tests, MESH: Plasmids, Drug Resistance, Multiple, Bacterial, MESH: Anti-Bacterial Agents, Madagascar, Animals, IncH1, Yersinia pseudotuberculosis, MESH: Animals, Pharmacology (medical), MESH: Doxycycline, pAAA83, Plague, Antiinfective agent, biology, MESH: Drug Resistance, Multiple, Bacterial, General Medicine, biology.organism_classification, MESH: DNA, Bacterial, Virology, Anti-Bacterial Agents, Rats, IncP, 3. Good health, pB71, Multiple drug resistance, Infectious Diseases, Salmonella enterica, Doxycycline, MESH: Disk Diffusion Antimicrobial Tests, Streptomycin, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Plasmids
Abstract: International audience; The emergence of antibiotic-resistant Yersinia pestis strains represents a public health concern. Two antibiotic-resistant Y. pestis strains isolated from Madagascar have been previously identified and characterised. Both strains carried conjugative plasmids that conferred resistance to streptomycin or to multiple antibacterial drugs, respectively. Here we characterised a novel Y. pestis strain (IP2180H) that exhibited resistance to doxycycline. This strain was isolated from a rat in Antananarivo (Madagascar) in 1998. Resistance was carried by a conjugative plasmid (pIP2180H) homologous to pB71 from Salmonella enterica. The plasmid of the previously identified streptomycin-resistant Y. pestis strain was also sequenced and it was found that the three antibiotic resistance Y. pestis plasmids sequenced until now are genetically unrelated and are also unrelated to multidrug resistance plasmids from the phylogenetically close bacterial species Yersinia pseudotuberculosis. The fact that the three antibiotic-resistant Malagasy Y. pestis strains were isolated from different hosts, at different times, from distant locations, and carried unrelated plasmids indicates independent horizontal acquisition of genetic material and further demonstrates the capacity of Y. pestis to acquire antibiotic resistance plasmids under natural conditions. Since these resistance plasmids can frequently carry or easily trap antibiotic resistance cassettes, the emergence of new multidrug-resistant Y. pestis strains may be expected and would represent a major health threat.
Published: 2018
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111. Absolute quantitation of microbes using 16S rRNA gene metabarcoding: A rapid normalization of relative abundances by quantitative PCR targeting a 16S rRNA gene spike‐in standard

Author: Jean Jacques Godon, Marie Léa De Almeida, Olivier Zemb, Laurent Cauquil, Jérôme Hamelin, Caroline S. Achard, Béatrice Gabinaud, Lisanne M G Verschuren, Génétique Physiologie et Systèmes d'Elevage (GenPhySE ), Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Lallemand SAS, Laboratoire de Biotechnologie de l'Environnement [Narbonne] (LBE), Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Topigs Norsvin Res Ctr BV, Livestock Research, Wageningen University and Research [Wageningen] (WUR), AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), France Génomique National, Agence Nationale pour la Recherche. Grant Number: ANR‐10‐INBS‐09, ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées
Subjects: [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], 16SrRNA gene, méthode de mesure, spike-in, lcsh:QR1-502, microbiome, Biotechnologies, Computational biology, Biology, Real-Time Polymerase Chain Reaction, Microbiology, lcsh:Microbiology, 16S rRNA gene, Absolute count data, Metabarcoding, Microbiome, Normalization, Spike‐in, 03 medical and health sciences, RNA, Ribosomal, 16S, Environmental Microbiology, DNA Barcoding, Taxonomic, Fokkerij & Genomica, Gene, Relative species abundance, Illumina dye sequencing, 030304 developmental biology, Gram, 0303 health sciences, communauté microbienne, Base Sequence, 030306 microbiology, Microbiota, absolute count data, High-Throughput Nucleotide Sequencing, Original Articles, Biodiversity, Sequence Analysis, DNA, 16S ribosomal RNA, DNA extraction, Hypervariable region, spike‐in, normalization, Real-time polymerase chain reaction, [SDE]Environmental Sciences, metabarcoding, Metagenome, Original Article, Metagenomics, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, Animal Breeding & Genomics
Abstract: Metabarcoding of the 16S rRNA gene is commonly used to characterize microbial communities, by estimating the relative abundance of microbes. Here, we present a method to retrieve the concentrations of the 16S rRNA gene per gram of any environmental sample using a synthetic standard in minuscule amounts (100 ppm to 1% of the 16S rRNA sequences) that is added to the sample before DNA extraction and quantified by two quantitative polymerase chain reaction (qPCR) reactions. This allows normalizing by the initial microbial density, taking into account the DNA recovery yield. We quantified the internal standard and the total load of 16S rRNA genes by qPCR. The qPCR for the latter uses the exact same primers as those used for Illumina sequencing of the V3‐V4 hypervariable regions of the 16S rRNA gene to increase accuracy. We are able to calculate the absolute concentration of the species per gram of sample, taking into account the DNA recovery yield. This is crucial for an accurate estimate as the yield varied between 40% and 84%. This method avoids sacrificing a high proportion of the sequencing effort to quantify the internal standard. If sacrificing a part of the sequencing effort to the internal standard is acceptable, we however recommend that the internal standard accounts for 30% of the environmental 16S rRNA genes to avoid the PCR bias associated with rare phylotypes. The method proposed here was tested on a feces sample but can be applied more broadly on any environmental sample. This method offers a real improvement of metabarcoding of microbial communities since it makes the method quantitative with limited efforts., Here, we present a spike‐and‐recovery method to get quantitative estimates from 16S rRNA surveys. The method relies on adding an artificial strand of DNA to the lysis buffer before the DNA extraction and measuring its recovery either by direct sequencing or by quantitative polymerase chain reaction (qPCR). The low detection limit achieved by qPCR allows to add minute amounts of the internal standard so that the sequencing effort is focused on the unknown sequences.
Published: 2020
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112. Impact of a resistance gene against a fungal pathogen on the plant host residue microbiome: the case of the Leptosphaeria maculans-Brassica napus pathosystem

Author: Marie-Hélène Balesdent, Lydie Kerdraon, Matthieu Barret, Frédéric Suffert, Valérie Laval, BIOlogie et GEstion des Risques en agriculture (BIOGER), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de Recherche en Horticulture et Semences (IRHS), Université d'Angers (UA)-AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), European Union Horizon Framework 2020 Program ('EMPHASIS Project', Grant Agreement no. 634179), France Génomique National Infrastructure : 'Investissement d’avenir' program managed by Agence Nationale pour la Recherche (contract ANR-10-INBS-09)., ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), European Project: 634179,H2020,H2020-SFS-2014-2,EMPHASIS(2015), Université d'Angers (UA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-INSTITUT AGRO Agrocampus Ouest, and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)
Subjects: 0106 biological sciences, ecological network analysis, [SDV.SA]Life Sciences [q-bio]/Agricultural sciences, microbial communities, microbiome, Biology, écological network analysis, 01 natural sciences, 03 medical and health sciences, Pathosystem, Leptosphaeria maculans, medicine, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, Microbiome, Pathogen, Disease Resistance, Plant Diseases, 030304 developmental biology, 2. Zero hunger, Canker, Genetics, 0303 health sciences, Host (biology), pathobiome, Microbiota, Brassica napus, Original Articles, 15. Life on land, medicine.disease, biology.organism_classification, oilseed rape residues, Sexual reproduction, [SDV.BV.PEP]Life Sciences [q-bio]/Vegetal Biology/Phytopathology and phytopharmacy, Colonisation, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Stem canker, Host-Pathogen Interactions, metabarcoding, Original Article, Leptosphaeria, 010606 plant biology & botany
Abstract: Oilseed rape residues are a crucial determinant of stem canker epidemiology as they support the sexual reproduction of the fungal pathogen Leptosphaeria maculans. The aim of this study was to characterize the impact of a resistance gene against L. maculans infection on residue microbial communities and to identify microorganisms interacting with this pathogen during residue degradation. We used near‐isogenic lines to obtain healthy and infected host plants. The microbiome associated with the two types of plant residues was characterized by metabarcoding. A combination of linear discriminant analysis and ecological network analysis was used to compare the microbial communities and to identify microorganisms interacting with L. maculans. Fungal community structure differed between the two lines at harvest, but not subsequently, suggesting that the presence/absence of the resistance gene influences the microbiome at the base of the stem whilst the plant is alive, but that this does not necessarily lead to differential colonization of the residues by fungi. Direct interactions with other members of the community involved many fungal and bacterial amplicon sequence variants (ASVs). L. maculans appeared to play a minor role in networks, whereas one ASV affiliated to Plenodomus biglobosus (synonym Leptosphaeria biglobosa) from the Leptosphaeria species complex may be considered a keystone taxon in the networks at harvest. This approach could be used to identify and promote microorganisms with beneficial effects against residue‐borne pathogens and, more broadly, to decipher the complex interactions between multispecies pathosystems and other microbial components in crop residues., Characterizing the impact of a resistance gene against Leptosphaeria maculans on the microbiome of oilseed rape residues using near‐isogenic lines helps to identify microorganisms interacting with this pathogen.
Published: 2020
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113. The impact of transposable elements on tomato diversity

Author: Marisol Domínguez, Medina Benchouaia, Elise Dugas, Vincent Colot, Leandro Quadrana, Basile Leduque, José M. Jiménez-Gómez, Colot, Vincent, Contribution des éléments transposables (ET) à la domestication et à l'amélioration de la tomate - - tomaTE2017 - ANR-17-CE20-0024 - AAPG2017 - VALID, Organisation et montée en puissance d'une Infrastructure Nationale de Génomique - - France-Génomique2010 - ANR-10-INBS-0009 - INBS - VALID, Institut de biologie de l'ENS Paris (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Jean-Pierre Bourgin (IJPB), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), France Genomique national infrastructure (MOMENTUM program), ANR-17-CE20-0024,tomaTE,Contribution des éléments transposables (ET) à la domestication et à l'amélioration de la tomate(2017), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Plateforme Génomique de l'IBENS, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, Agence National de la Recherche (ANR-17-tomaTE to V.C. and J.J.G.), the Centre National de la Recherche Scientifique (MOMENTUM program to L.Q.), and France Génomique national infrastructure, funded as part of the Investissements d’Avenir program managed by the Agence Nationale de la Recherche (ANR-10-INBS-09)., GenomiqueENS (Genomique ENS), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Département de Biologie - ENS Paris, Bodescot, Myriam, Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Département de Biologie - ENS Paris
Subjects: 0106 biological sciences, 0301 basic medicine, Transposable element, media_common.quotation_subject, Science, [SDV]Life Sciences [q-bio], Plant genetics, General Physics and Astronomy, Single-nucleotide polymorphism, Genome-wide association study, Biology, Transcript isoforms, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, 01 natural sciences, Genome, General Biochemistry, Genetics and Molecular Biology, [SDV.GEN.GPL]Life Sciences [q-bio]/Genetics/Plants genetics, 03 medical and health sciences, [SDV.GEN.GPL] Life Sciences [q-bio]/Genetics/Plants genetics, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.BID.EVO] Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, [SDV.BV] Life Sciences [q-bio]/Vegetal Biology, Allele, lcsh:Science, Gene, 030304 developmental biology, media_common, Genetic association, 2. Zero hunger, 0303 health sciences, Multidisciplinary, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], fungi, food and beverages, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, General Chemistry, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], 030104 developmental biology, Evolutionary biology, [SDV.GEN.GPO] Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], lcsh:Q, Gene pool, Diversity (politics), 010606 plant biology & botany
Abstract: Tomatoes come in a multitude of shapes and flavors despite a narrow genetic pool. Here, we leveraged whole-genome resequencing data available for 602 cultivated and wild accessions to determine the contribution of transposable elements (TEs) to tomato diversity. We identified 6,906 TE insertions polymorphisms (TIPs), which result from the mobilization of 337 distinct TE families. Most TIPs are low frequency variants and disproportionately located within or adjacent to genes involved in environmental response. In addition, we show that genic TE insertions tend to have strong transcriptional effects and can notably lead to the generation of multiple transcript isoforms. We also uncovered through genome-wide association studies (GWAS) ~180 TIPs associated with extreme variations in major agronomic traits or secondary metabolites. Importantly, these TIPs tend to affect loci that are distinct from those tagged by SNPs. Collectively, our findings suggest a unique and important role for TE mobilization in tomato diversification, with important implications for future breeding.
Published: 2020
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114. Independent origin of XY and ZW sex determination mechanisms in Mosquitofish sister species

Author: Susanne Kneitz, Frederik Helmprobst, Hugues Parrinello, Céline Lopez-Roques, Kang Du, Indrajit Nanda, Romain Feron, Verena A. Kottler, Dunja K. Lamatsch, Christophe Klopp, Laurent Journot, Manfred Schartl, Jérôme Lluch, Yann Guiguen, University of Würzburg = Universität Würzburg, Laboratoire de Physiologie et Génomique des Poissons (LPGP), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institute of Bioinformatics, GSF - Research Institute for Environment and Health, Unité de Mathématiques et Informatique Appliquées de Toulouse (MIAT INRA), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University of Innsbruck, Génome et Transcriptome - Plateforme Génomique (GeT-PlaGe), Institut National de la Recherche Agronomique (INRA)-Plateforme Génome & Transcriptome (GET), Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Montpellier (UM), Hagler Institute for Advanced Study and Department of Biology, Texas A&M University System, This project was supported by funds to Y.G. and M.S. from the 'Agence Nationale de la Recherche' and the 'Deutsche Forschungsgemeinschaft' (ANR/DFG, PhyloSex project, 2014-2016). V.A.K. was supported through a SCIENTIA fellowship of the Free State of Bavaria. The GeT, Toulouse (C.L.-R., J.L.), and the Montpellier GenomiX (MGX) France (L.J., H.P.) core facilities were supported by France Génomique National infrastructure, funded as part of 'Investissement d’avenir' program managed by Agence Nationale pour la Recherche (contract ANR-10-INBS-09)., ANR-13-ISV7-0005,PhyloSex,Evolution des déterminants majeurs du sexe chez les poissons.(2013), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3)
Subjects: Male, 0106 biological sciences, X Chromosome, Genetic Linkage, 46, XX Testicular Disorders of Sex Development, [SDV]Life Sciences [q-bio], sex determination, Locus (genetics), sox9b, Investigations, Y chromosome, 010603 evolutionary biology, 01 natural sciences, Gambusia, Cyprinodontiformes, 03 medical and health sciences, Y Chromosome, Genetics, Animals, gipc1, Cell Lineage, [INFO]Computer Science [cs], Allele, Phylogeny, 030304 developmental biology, 0303 health sciences, [SDV.GEN]Life Sciences [q-bio]/Genetics, Genome, Sex Chromosomes, Autosome, biology, Mosquitofish, Pigmentation, Chromosome Mapping, Chromosome, Eastern mosquitofish, Sex Determination Processes, biology.organism_classification, W chromosome, [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, Phenotype, Female, pool sequencing
Abstract: Fish are known for the outstanding variety of their sex determination mechanisms and sex chromosome systems. The western (Gambusia affinis) and eastern mosquitofish (G. holbrooki) are sister species for which different sex determination mechanisms have been described: ZZ/ZW for G. affinis and XX/XY for G. holbrooki. Here, we carried out restriction-site associated DNA (RAD-) and pool sequencing (Pool-seq) to characterize the sex chromosomes of both species. We found that the ZW chromosomes of G. affinis females and the XY chromosomes of G. holbrooki males correspond to different linkage groups, and thus evolved independently from separate autosomes. In interspecific hybrids, the Y chromosome is dominant over the W chromosome, and X is dominant over Z. In G. holbrooki, we identified a candidate region for the Y-linked melanic pigmentation locus, a rare male phenotype that constitutes a potentially sexually antagonistic trait and is associated with other such characteristics, e.g., large body size and aggressive behavior. We developed a SNP-based marker in the Y-linked allele of GIPC PDZ domain containing family member 1 (gipc1), which was linked to melanism in all tested G. holbrooki populations. This locus represents an example for a color locus that is located in close proximity to a putative sex determiner, and most likely substantially contributed to the evolution of the Y.
Published: 2020
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115. Sex chromosome and sex locus characterization in goldfish, Carassius auratus (Linnaeus, 1758)

Author: Ming, Wen, Romain, Feron, Qiaowei, Pan, Justine, Guguin, Elodie, Jouanno, Amaury, Herpin, Christophe, Klopp, Cedric, Cabau, Margot, Zahm, Hugues, Parrinello, Laurent, Journot, Shawn M, Burgess, Yoshihiro, Omori, John H, Postlethwait, Manfred, Schartl, Yann, Guiguen, Hunan Normal University, Laboratoire de Physiologie et Génomique des Poissons (LPGP), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), University of Lausanne, Lausanne, Switzerland, Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne (UNIL), Plateforme Bio-Informatique - Génotoul, Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Système d'Information des GENomes des Animaux d'Elevage (SIGENAE), Institut de Génomique Fonctionnelle - Montpellier GenomiX (IGF MGX), Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), National Human Genome Research Institute (NHGRI), Nagahama Institute of Bioscience and Technology, Osaka University [Osaka], University of Oregon [Eugene], University of Würzburg, Texas State University, Grant-in-Aid for Scientific Research (19 K22426) - Grants: R01OD011116 and 5R01GM085318 from the USA National Institutes of Health - ANAEE-France National infrastructure, ANR-13-ISV7-0005,PhyloSex,Evolution des déterminants majeurs du sexe chez les poissons.(2013), ANR-10- INBS0009,INBS,France-Génomique, Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), State Key Laboratory of Developmental Biology of Freshwater Fish, Hunan University [Changsha] (HNU), University of Lausanne (UNIL), Département d'écologie et évolution [Lausanne] (DEE), Génétique Physiologie et Systèmes d'Elevage (GenPhySE ), Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Unité de Mathématiques et Informatique Appliquées de Toulouse (MIAT INRA), Centre National de la Recherche Scientifique (CNRS)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Centre National de la Recherche Scientifique (CNRS)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1), Institute for Protein Research [Osaka], Nagahama Institute of Bio-Science and Technology, Oregon State University (OSU), 'Agence Nationale de la Recherche' and the 'Deutsche Forschungsgemeinschaft' (ANR/DFG,PhyloSex project, 2014–2016) to MS and YG. Montpellier Genomics (MGX)facility was supported by France Génomique National infrastructure, fundedas part of 'Investissement d’avenir' program managed by Agence Nationalepour la Recherche (contract ANR-10-INBS-09). This work was also supportedby Grant-in-Aid for Scientific Research (19 K22426) to YO, and grantsR01OD011116 and 5R01GM085318 from the USA National Institutes of Healthto JHP. INRAE-U3E was supported by a PEARL INRAE 1036 U3E funding fromthe ANAEE-France National infrastructure., ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université de Lausanne = University of Lausanne (UNIL), Unité de Mathématiques et Informatique Appliquées de Toulouse (MIAT INRAE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-BioCampus (BCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Naudinat, Carine, Organisation et montée en puissance d'une Infrastructure Nationale de Génomique - - France-Génomique2010 - ANR-10-INBS-0009 - INBS - VALID, and Blanc – Accords bilatéraux 2013 - Evolution des déterminants majeurs du sexe chez les poissons. - - PhyloSex2013 - ANR-13-ISV7-0005 - Blanc – Accords bilatéraux 2013 - VALID
Subjects: Male, Male genome assembly, [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], Sex Chromosomes, lcsh:QH426-470, Sex markers, Genetic Linkage, [SDV.OT] Life Sciences [q-bio]/Other [q-bio.OT], lcsh:Biotechnology, [SDV]Life Sciences [q-bio], Poolseq, RADseq, Sex Determination Processes, Sex determination, [SDV] Life Sciences [q-bio], lcsh:Genetics, Y Chromosome, lcsh:TP248.13-248.65, Goldfish, Animals, Female, Goldfish/genetics, Sex Chromosomes/genetics, Sex Determination Processes/genetics, Research Article
Abstract: International audience; Background - Goldfish is an important model for various areas of research, including neural development and behavior and a species of significant importance in aquaculture, especially as an ornamental species. It has a male heterogametic (XX/XY) sex determination system that relies on both genetic and environmental factors, with high temperatures being able to produce female-to-male sex reversal. Little, however, is currently known on the molecular basis of genetic sex determination in this important cyprinid model. Here we used sequencing approaches to better characterize sex determination and sex-chromosomes in an experimental strain of goldfish. Results - Our results confirmed that sex determination in goldfish is a mix of environmental and genetic factors and that its sex determination system is male heterogametic (XX/XY). Using reduced representation (RAD-seq) and whole genome (pool-seq) approaches, we characterized sex-linked polymorphisms and developed male specific genetic markers. These male specific markers were used to distinguish sex-reversed XX neomales from XY males and to demonstrate that XX female-to-male sex reversal could even occur at a relatively low rearing temperature (18 °C), for which sex reversal has been previously shown to be close to zero. We also characterized a relatively large non-recombining region (~ 11.7 Mb) on goldfish linkage group 22 (LG22) that contained a high-density of male-biased genetic polymorphisms. This large LG22 region harbors 373 genes, including a single candidate as a potential master sex gene, i.e., the anti-Mullerian hormone gene (amh). However, no sex-linked polymorphisms were detected in the coding DNA sequence of the goldfish amh gene. Conclusions - These results show that our goldfish strain has a relatively large sex locus on LG22, which is likely the Y chromosome of this experimental population. The presence of a few XX males even at low temperature also suggests that other environmental factors in addition to temperature could trigger female-to-male sex reversal. Finally, we also developed sex-linked genetic markers, which will be important tools for future research on sex determination in our experimental goldfish population. However, additional work would be needed to explore whether this sex locus is conserved in other populations of goldfish.
Published: 2020
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116. Genomic determinants for initiation and length of natural antisense transcripts in Entamoeba histolytica

Author: Nancy Guillén, Chung-Chau Hon, Jean-Yves Coppée, Mikael Koutero, Christian Weber, Damien Mornico, Marie-Agnès Dillies, coppee, jean-yves, Génomique, Biotechnologies végétales - Comprendre la pathogenicité de Entamoeba par l'utilisation de la transcriptomique et la phylogénétique comparatives - - GENAMIBE2010 - ANR-10-GENM-0011 - Génomique - VALID, Organisation et montée en puissance d'une Infrastructure Nationale de Génomique - - France-Génomique2010 - ANR-10-INBS-0009 - INBS - VALID, Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), RIKEN Center for Integrative Medical Sciences [Yokohama] (RIKEN IMS), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), Biologie Cellulaire du Parasitisme, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Transcriptome et Epigénome (PF2), Institut Pasteur [Paris] (IP), Biologie des Interactions Hôte-Parasite - Biology of Host-Parasite Interactions, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), The work was funded by the National French Research Agency (ANR-2010-GENM-0011-01, GENAMIBE). The Transcriptome and Epigenome Platform is a member of the France Génomique consortium (ANR10-NBS-09-08)., ANR-10-GENM-0011,GENAMIBE,Comprendre la pathogenicité de Entamoeba par l'utilisation de la transcriptomique et la phylogénétique comparatives(2010), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris], and Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, endocrine system, Transcription, Genetic, Polyadenylation, [SDV]Life Sciences [q-bio], lcsh:Medicine, Biology, Genome, Article, 03 medical and health sciences, Entamoeba histolytica, MESH: Gene Expression Profiling, Transcription (biology), Gene expression, RNA, Antisense, MESH: RNA, Antisense, Transcriptomics, lcsh:Science, Gene, Genetics, Multidisciplinary, 030102 biochemistry & molecular biology, Gene Expression Profiling, MESH: Transcription, Genetic, lcsh:R, fungi, Parasite genomics, RNA, MESH: Entamoeba histolytica, biology.organism_classification, Gene expression profiling, [SDV] Life Sciences [q-bio], 030104 developmental biology, lcsh:Q
Abstract: Natural antisense transcripts (NAT) have been reported in prokaryotes and eukaryotes. While the functions of most reported NATs remain unknown, their potentials in regulating the transcription of their counterparts have been speculated. Entamoeba histolytica, which is a unicellular eukaryotic parasite, has a compact protein-coding genome with very short intronic and intergenic regions. The regulatory mechanisms of gene expression in this compact genome are under-described. In this study, by genome-wide mapping of RNA-Seq data in the genome of E. histolytica, we show that a substantial fraction of its protein-coding genes (28%) has significant transcription on their opposite strand (i.e. NAT). Intriguingly, we found the location of transcription start sites or polyadenylation sites of NAT are determined by the specific motifs encoded on the opposite strand of the gene coding sequences, thereby providing a compact regulatory system for gene transcription. Moreover, we demonstrated that NATs are globally up-regulated under various environmental conditions including temperature stress and pathogenicity. While NATs do not appear to be consequences of spurious transcription, they may play a role in regulating gene expression in E. histolytica, a hypothesis which needs to be tested.
Published: 2020
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117. Sex chromosome and sex locus characterization in the goldfish, Carassius auratus

Author: Hugues Parrinello, Amaury Herpin, Margot Zahm, Romain Feron, Manfred Schartl, Ming Wen, Shawn M. Burgess, Elodie Jouanno, Qiaowei Pan, Yann Guiguen, Laurent Journot, Christophe Klopp, Justine Guguin, Cédric Cabau, John H. Postlethwait, Yoshihiro Omori, Laboratoire de Physiologie et Génomique des Poissons (LPGP), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Recherche Agronomique (INRA), Hunan Normal University, University of Lausanne (UNIL), Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne (UNIL), Department of Ecology and Evolution, Unité de Mathématiques et Informatique Appliquées de Toulouse (MIAT INRA), Institut National de la Recherche Agronomique (INRA), Génétique Physiologie et Systèmes d'Elevage (GenPhySE ), École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Institut de Génomique Fonctionnelle - Montpellier GenomiX (IGF MGX), Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), National Human Genome Research Institute (NHGRI), Nagahama Institute of Bio-Science and Technology, Osaka University, Institute of Neuroscience, University of Oregon [Eugene], University of Würzburg, Texas State University, This project was supported by funds from the 'Agence Nationale de la Recherche' and the 'Deutsche Forschungsgemeinschaft' (ANR/DFG, PhyloSex project, 2014-2016) to MS and YG. Montpellier Genomics (MGX) facility was supported by France Génomique National infrastructure, funded as part of 'Investissement d’avenir' program managed by Agence Nationale pour la Recherche (contract ANR-10-INBS-09). This work was also supported by Grant-in-Aid for Scientific Research (19K22426) to YO, and grants R01OD011116 and 5R01GM085318 from the USA National Institutes of Health to JHP, ANR-13-ISV7-0005,PhyloSex,Evolution des déterminants majeurs du sexe chez les poissons.(2013), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), ProdInra, Migration, Blanc – Accords bilatéraux 2013 - Evolution des déterminants majeurs du sexe chez les poissons. - - PhyloSex2013 - ANR-13-ISV7-0005 - Blanc – Accords bilatéraux 2013 - VALID, Organisation et montée en puissance d'une Infrastructure Nationale de Génomique - - France-Génomique2010 - ANR-10-INBS-0009 - INBS - VALID, Institut National de la Recherche Agronomique (INRA)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hunan Normal University (HNU), Université de Lausanne = University of Lausanne (UNIL), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-École nationale supérieure agronomique de Toulouse [ENSAT], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-BioCampus (BCM), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0106 biological sciences, male genome assembly, [SDV]Life Sciences [q-bio], marqueur génétique, sex determination, Locus (genetics), [MATH] Mathematics [math], [SDV.GEN] Life Sciences [q-bio]/Genetics, [SDV.GEN.GA] Life Sciences [q-bio]/Genetics/Animal genetics, [INFO] Computer Science [cs], Biology, Y chromosome, 010603 evolutionary biology, 01 natural sciences, Genome, reproduction, 03 medical and health sciences, poisson, cyprinidae, température, Sex-determination system, chromosome sexuel, [INFO]Computer Science [cs], 14. Life underwater, goldfish, [MATH]Mathematics [math], Gene, poolseq, 030304 developmental biology, Genetics, 0303 health sciences, [SDV.GEN]Life Sciences [q-bio]/Genetics, détermination du sexe, génome, carassius auratus, RADseq, Sex reversal, [SDV] Life Sciences [q-bio], poisson rouge, [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, espèce modèle, aquaculture, Genetic marker, facteur externe, sex markers, Heterogametic sex
Abstract: BackgroundGoldfish is an important model for various areas of research, including neural development and behavior and a species of significant importance in aquaculture, especially as an ornamental species. It has a male heterogametic (XX/XY) sex determination system that relies on both genetic and environmental factors, with high temperatures being able to produce female-to-male sex reversal. Little, however, is currently known on the molecular basis of genetic sex determination in this important cyprinid model. We used sequencing approaches to better characterize sex determination and sex-chromosomes in goldfish.ResultsOur results confirmed that sex determination in goldfish is a mix of environmental and genetic factors and that its sex determination system is male heterogametic (XX/XY). Using reduced representation (RAD-seq) and whole genome (pool-seq) approaches, we characterized sex-linked polymorphisms and developed male specific genetic markers. These male specific markers were used to distinguish sex-reversed XX neomales from XY males and to demonstrate that XX female-to-male sex reversal could even occur at a relatively low rearing temperature (18°C), for which sex reversal has been previously shown to be close to zero. We also characterized a relatively large non-recombining region (∼11.7 Mb) on goldfish linkage group 22 (LG22) that contained a high-density of male-biased genetic polymorphisms. This large LG22 region harbors 373 genes, including a single candidate as a potential master sex gene, i.e., the anti-Mullerian hormone gene (amh). However, no sex-linked polymorphisms were detected in the goldfish amh gene or its 5 kb proximal promoter sequence.ConclusionsThese results show that goldfish have a relatively large sex locus on LG22, which is likely the goldfish Y chromosome. The presence of a few XX males even at low temperature also suggests that other environmental factors in addition to temperature could trigger female-to-male sex reversal. Finally, we also developed sex-linked genetic markers in goldfish, which will be important for future research on sex determination and aquaculture applications in this species.
Published: 2019
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118. High throughput, error corrected Nanopore single cell transcriptome sequencing

Author: Rainer Waldmann, Pascal Barbry, Virginie Magnone, Kevin Lebrigand, Institut de pharmacologie moléculaire et cellulaire (IPMC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), This project was funded by grants from the Institut National contre le Cancer (PLBIO2018-156), the Conseil Départemental des Alpes Maritimes (2016-294DGADSH-CV), FRM (DEQ20180339158), the Inserm Cross-cutting Scientific Program HuDeCA 2018, the National Infrastructure France Génomique (Commissariat aux Grands Investissements, ANR-10-INBS-09-03, ANR-10-INBS-09-02). This publication is part of the Human Cell Atlas - https://www.humancellatlas.org/publications., and ANR-19-P3IA-0002,3IA@cote d'azur,3IA Côte d'Azur(2019)
Subjects: 0301 basic medicine, Computer science, Bioinformatics, [SDV]Life Sciences [q-bio], Science, General Physics and Astronomy, Gene Expression, Genomics, 02 engineering and technology, Computational biology, General Biochemistry, Genetics and Molecular Biology, Deep sequencing, Article, 03 medical and health sciences, Mice, Nanopores, 0302 clinical medicine, Genome-wide analysis of gene expression, Single cell transcriptome, Animals, Protein Isoforms, Cell isolation, Receptors, AMPA, lcsh:Science, Throughput (business), 030304 developmental biology, 0303 health sciences, Multidisciplinary, Sequence Analysis, RNA, Gene Expression Profiling, Brain, High-Throughput Nucleotide Sequencing, General Chemistry, Sequence Analysis, DNA, 021001 nanoscience & nanotechnology, Mice, Inbred C57BL, Nanopore, Nanopore Sequencing, 030104 developmental biology, Single cell sequencing, RNA editing, RNA splicing, lcsh:Q, Nanopore sequencing, 0210 nano-technology, Transcriptome, 030217 neurology & neurosurgery
Abstract: Droplet-based high throughput single cell sequencing techniques tremendously advanced our insight into cell-to-cell heterogeneity. However, those approaches only allow analysis of one extremity of the transcript after short read sequencing. In consequence, information on splicing and sequence heterogeneity is lost. To overcome this limitation, several approaches that use long-read sequencing were introduced recently. Yet, those techniques are limited by low sequencing depth and/or lacking or inaccurate assignment of unique molecular identifiers (UMIs), which are critical for elimination of PCR bias and artifacts. We introduce ScNaUmi-seq, an approach that combines the high throughput of Oxford Nanopore sequencing with an accurate cell barcode and UMI assignment strategy. UMI guided error correction allows to generate high accuracy full length sequence information with the 10x Genomics single cell isolation system at high sequencing depths. We analyzed transcript isoform diversity in embryonic mouse brain and show that ScNaUmi-seq allows defining splicing and SNVs (RNA editing) at a single cell level., Droplet-based high throughput single cell sequencing techniques can often lose information on transcript splicing and heterogenity. Here the authors introduce ScNaUmi-seq, which uses Oxford Nanopore sequencing and barcoding to generate high accuracy full length sequences.
Published: 2019
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119. Compatibility of 5-ethynyl-2′F-ANA UTP with in vitro selection for the generation of base-modified, nuclease resistant aptamers

Author: Marcel Hollenstein, Adam Katolik, Pascal Röthlisberger, Christian J. Leumann, Fabienne Levi-Acobas, Ivo Sarac, Thomas Cokelaer, Masad J. Damha, Chimie bioorganique des acides nucléiques - Bioorganic chemistry of nucleic acids, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Département de Génomes et Génétique - Department of Genomes and Genetics, Institut Pasteur [Paris], University of Bern, McGill University = Université McGill [Montréal, Canada], Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Biomics (plateforme technologique), This work was financially supported by Institut Pasteur (starting grant to M. H.), France Génomique (ANR-10-INBS-09-09) and IBISA (to T. C.), the Natural Science and Engineering Council of Canada (Discovery grant to MJD), and the Swiss National Science Foundation (200020-146646 to C. J. L.)., ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris] (IP)
Subjects: 0301 basic medicine, Aptamer, Uridine Triphosphate, 010402 general chemistry, 01 natural sciences, Biochemistry, Primer extension, Nucleobase, 03 medical and health sciences, chemistry.chemical_compound, 540 Chemistry, Carbohydrate Conformation, [CHIM]Chemical Sciences, Nucleotide, Physical and Theoretical Chemistry, chemistry.chemical_classification, Nuclease, Binding Sites, biology, Oligonucleotide, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Organic Chemistry, DNA, Aptamers, Nucleotide, 500 Science, Arabinose, 0104 chemical sciences, 030104 developmental biology, chemistry, biology.protein, 570 Life sciences, Systematic evolution of ligands by exponential enrichment
Abstract: International audience; A modified nucleoside triphosphate bearing two modifications based on a 2'-deoxy-2'-fluoro-arabinofuranose sugar and a uracil nucleobase equipped with a C5-ethynyl moiety (5-ethynyl-2'F-ANA UTP) was synthesized. This nucleotide analog could enzymatically be incorporated into DNA oligonucleotides by primer extension and reverse transcribed to unmodified DNA. This nucleotide could be used in SELEX for the identification of high binding affinity and nuclease resistant aptamers.
Published: 2019
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120. Genome Sequences of Three Nocardia cyriacigeorgica Strains and One Nocardia asteroides Strain

Author: Emmanuelle Bergeron, Christophe Martin, Petar Pujic, Veronica Rodriguez-Nava, Thierry Winiarski, Florian Vautrin, Benoit Cournoyer, Vanessa Louzier, Danis Abrouk, Audrey Dubost, Laboratoire d'Ecologie Microbienne - UMR 5557 (LEM), Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Lyon (ENVL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Laboratoire d'Ecologie des Hydrosystèmes Naturels et Anthropisés (LEHNA), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École Nationale des Travaux Publics de l'État (ENTPE), Observatoire Français des Nocardioses [Hôpital de la Croix-Rousse, CHU-HCL] (Institut des Agents Infectieux - IAI), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Centre de Biologie et Pathologie Nord [Hôpital de la Croix-Rousse, CHU-HCL], Agressions Pulmonaires et Circulatoires dans le Sepsis - UR (APCSé), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), The LABGeM (CEA/Genoscope and CNRS UMR8030), the France Génomique, and The French Institute of Bioinformatics (funded as part of the Investissement d’Avenir program managed by the Agence Nationale pour la Recherche, contracts ANR-10-INBS-09, ANR-11-INBS-0013) are all thanked for their support to the MicroScope annotation platform., ANR-10-INBS-09-01/10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), ANR-11-INBS-0013/11-INBS-0013,ReNaBi-IFB,Institut français de bioinformatique(2011), ANR-17-CE04-0010,INFILTRON,Dispositif INFILTRON pour une évaluation des fonctions infiltration & filtration des sols urbains dans un contexte de gestion des eaux pluviales(2017), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Ecole Nationale Vétérinaire de Lyon (ENVL)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École Nationale des Travaux Publics de l'État (ENTPE)-Centre National de la Recherche Scientifique (CNRS), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), ANR-11-INBS-0013,IFB (ex Renabi-IFB),Institut français de bioinformatique(2011), Cournoyer, Benoit, Organisation et montée en puissance d'une Infrastructure Nationale de Génomique - - France-Génomique2010 - ANR-10-INBS-0009 - INBS - VALID, Infrastructures - Institut français de bioinformatique - - IFB (ex Renabi-IFB)2011 - ANR-11-INBS-0013 - INBS - VALID, Dispositif INFILTRON pour une évaluation des fonctions infiltration & filtration des sols urbains dans un contexte de gestion des eaux pluviales - - INFILTRON2017 - ANR-17-CE04-0010 - AAPG2017 - VALID, Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Ecole Nationale Vétérinaire de Lyon (ENVL), Centre de Biologie et Pathologie Nord [Hôpital de la Croix-Rousse, CHU-HCL]-Hôpital de la Croix-Rousse [CHU - HCL], and Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)
Subjects: [SDE] Environmental Sciences, 0301 basic medicine, 030106 microbiology, Biology, Genome, Microbiology, 03 medical and health sciences, Immunology and Microbiology (miscellaneous), nocardia astéroïdes, cellule souche, Genetics, NOCARDIA CYRIACIGEORGICA, Molecular Biology, integumentary system, Strain (biology), Microbiology and Parasitology, Genome Sequences, Nocardia, bacterial infections and mycoses, Pathogenicity, biology.organism_classification, Microbiologie et Parasitologie, facteur de pathogénicité, séquence du génome, [SDE.BE] Environmental Sciences/Biodiversity and Ecology, 030104 developmental biology, [SDE]Environmental Sciences, bacteria, [SDE.BE]Environmental Sciences/Biodiversity and Ecology
Abstract: We report four draft genome sequences of Nocardia spp. The strains are the Nocardia cyriacigeorgica DSM 44484 pathogenic type strain; two environmental isolates, Nocardia cyriacigeorgica EML446 and EML1456; and the Nocardia asteroides ATCC 19247 nonpathogenic type strain, with estimated genome sizes of 6.3 to 6.8 Mb. The study of these isolates will provide insight into physiology, evolution, and pathogenicity of Nocardia spp.
Published: 2019
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121. Transcriptome of tambaqui Colossoma macropomum during gonad differentiation: Different molecular signals leading to sex identity

Author: Dany Severac, Vanessa Ribeiro Reis, Fernanda Loureiro de Almeida, Yann Guiguen, Gilvan Ferreira da Silva, Aldessandro da Costa Amaral, Áquila Rodrigues do Nascimento, Igor Kelvyn Cavalcante Lobo, Michel Eduardo Beleza Yamagishi, Embrapa Amazônia Ocidental, Embrapa Informática Agropecuária, Laboratoire de Physiologie et Génomique des Poissons (LPGP), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de Génomique Fonctionnelle - Montpellier GenomiX (IGF MGX), Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Universidade Federal do Amazonas, The study wasfinancially supported by Embrapa (SEG03.13.09.010.00.00), the fellowship grants were supported by ADAPTA-II (465540/2014-7) to Igor Kelvyn Cavalcante Lobo and by CAPES to Vanessa Ribeiro Reis, France Génomique National infrastructure funded as part of Investissement d'avenir 'program managed by Agence Nationale pour la Recherche (contract ANR-10-INBS-09), and ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010)
Subjects: 0106 biological sciences, Male, Gonad, Sex Differentiation, Tambaqui, [SDV]Life Sciences [q-bio], Population, Serrasalmide, 01 natural sciences, Mâle, Transcriptome, 03 medical and health sciences, Testis, Genetics, medicine, Juvenile, Expression des gènes, Animals, 14. Life underwater, education, Gonadal Steroid Hormones, Gene, Colossoma macropomum, Wnt Signaling Pathway, 030304 developmental biology, Reproduction animale, 0303 health sciences, education.field_of_study, Sexual differentiation, biology, Wnt/beta-catenin pathway, Détermination du sexe, Ovary, Wnt signaling pathway, Femelle, biology.organism_classification, Différenciation sexuelle, Poisson, Biosynthetic Pathways, medicine.anatomical_structure, Female, Sequençage, Characiformes, 010606 plant biology & botany
Abstract: International audience; Tambaqui (Colossoma macropomum) is the major native species in Brazilian aquaculture, and we have shown that females exhibit a higher growth compared to males, opening up the possibility for the production of all-female population. To date, there is no information on the sex determination and differentiation molecular mechanisms of tambaqui. In the present study, transcriptome sequencing of juvenile trunks was performed to understand the molecular network involved in the gonadal sex differentiation. The results showed that before differentiation, components of the Wnt/beta-catenin pathway, fox and fst genes imprint female sex development, whereas antagonistic pathways (gsk3b, wt1 and fgfr2), sox9 and genes for androgen synthesis indicate male differentiation. Hence, in undifferentiated tambaqui, the Wnt/beta-catenin exerts a role on sex differentiation, either upregulated in female-like individuals, or antagonized in male-like individuals.
Published: 2019
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122. NF-Y controls fidelity of transcription initiation at gene promoters through maintenance of the nucleosome-depleted region

Author: Oldfield, Andrew, Henriques, Telmo, Kumar, Dhirendra, Burkholder, Adam, Cinghu, Senthilkumar, Paulet, Damien, Bennett, Brian, Yang, Pengyi, Scruggs, Benjamin, Lavender, Christopher, Rivals, Eric, Adelman, Karen, Jothi, Raja, Epigenetics and Stem Cell Biology Laboratory [Durham] (ESCBL-NIEHS-NIH), National Institute of Environmental Health Sciences [Durham] (NIEHS-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Harvard Medical School [Boston] (HMS), Maharishi Valmiki Hospital, Méthodes et Algorithmes pour la Bioinformatique (MAB), Laboratoire d'Informatique de Robotique et de Microélectronique de Montpellier (LIRMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Computationnelle (IBC), Institut National de la Recherche Agronomique (INRA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Marquette University, National Institutes of Health [Bethesda] (NIH), ATGC bioinformatics platform Montpellier. the Institut de Biologie Computationnelle (ANR-11-BINF-0002) Institut Français de Bioinformatique (ANR-11-INBS-0013)GEM Flagship project funded from Labex NUMEV (ANR-10-LABX-0020)France Génomique., ANR-10-LABX-0020/10-LABX-0020,NUMEV,Digital and Hardware Solutions and Modeling for the Environement and Life Sciences(2010), ANR-11-INBS-0013/11-INBS-0013,ReNaBi-IFB,Institut français de bioinformatique(2011), ANR-11-BINF-0002,IBC,Institut de Biologie Computationnelle de Montpellier(2011), ANR-10-INBS-09-01/10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Université de Montpellier (UM)-Institut National de la Recherche Agronomique (INRA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS), Marquette University [Milwaukee], ANR-10-LABX-0020,NUMEV,Digital and Hardware Solutions and Modeling for the Environement and Life Sciences(2010), ANR-11-INBS-0013,IFB (ex Renabi-IFB),Institut français de bioinformatique(2011), ANR-11-BINF-0002,IBC,Institut de biologie Computationnelle(2011), and ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010)
Subjects: Site Transcription Initiation, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Small Interfering, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Chromatin, Nucleosomes, Promoter Regions, Mice, Metabolism, CCAAT-Binding Factor, Gene Knockdown Techniques, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], RNA, Transcription Initiation Site, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Embryonic Stem Cells
Abstract: International audience; Faithful transcription initiation is critical for accurate gene expression, yet the mechanisms underlying specific transcription start site (TSS) selection in mammals remain unclear. Here, we show that the histone-fold domain protein NF-Y, a ubiquitously expressed transcription factor, controls the fidelity of transcription initiation at gene promoters in mouse embryonic stem cells. We report that NF-Y maintains the region upstream of TSSs in a nucleosome-depleted state while simultaneously protecting this accessible region against aberrant and/or ectopic transcription initiation. We find that loss of NF-Y binding in mammalian cells disrupts the promoter chromatin landscape, leading to nucleosomal encroachment over the canonical TSS. Importantly, this chromatin rearrangement is accompanied by upstream relocation of the transcription pre-initiation complex and ectopic transcription initiation. Further, this phenomenon generates aberrant extended transcripts that undergo translation, disrupting gene expression profiles. These results suggest NF-Y is a central player in TSS selection in metazoans and highlight the deleterious consequences of inaccurate transcription initiation.
Published: 2019
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123. Transcriptional profiling of a laboratory and clinical Mycobacterium tuberculosis strain suggests respiratory poisoning upon exposure to delamanid

Author: Jean-Yves Coppée, Odile Sismeiro, Pieter-Jan Ceyssens, Rachel Legendre, Hugo Varet, Amandine Sury, An Van den Bossche, Vanessa Mathys, Maladies bactériennes = Bacterial diseases [Bruxelles], Sciensano [Bruxelles], Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre National de Référence pour la tuberculose et les mycobactéries = National Reference Center for tuberculosis and mycobacteria [Bruxelles] (NRC Tuberc&myco), Transcriptome et Epigénome (PF2), Institut Pasteur [Paris], Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), The Transcriptome and Epigenome Platform is a member of the France Génomique consortium (ANR-10‐NBS‐09‐08). This research was supported by an International Network of Institute Pasteur: ACIP grant N°03–2016 from the Institute Pasteur in Paris., ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), Institut Pasteur [Paris] (IP), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, MESH: Mycobacterium tuberculosis, [SDV]Life Sciences [q-bio], Antitubercular Agents, Transcriptome, chemistry.chemical_compound, Cell Wall, MESH: Sequence Analysis, RNA, Oxazoles, media_common, MESH: Microbial Sensitivity Tests, MESH: Gene Expression Regulation, Bacterial, Genome, biology, MESH: Oxazoles, RNA sequencing, Aerobiosis, 3. Good health, RNA, Bacterial, Infectious Diseases, Nitroimidazoles, Delamanid, MESH: RNA, Bacterial, medicine.drug, Microbiology (medical), Drug, Tuberculosis, media_common.quotation_subject, 030106 microbiology, Immunology, Microbial Sensitivity Tests, Microbiology, Mycobacterium tuberculosis, 03 medical and health sciences, MESH: Gene Expression Profiling, MESH: Cell Wall, MESH: Aerobiosis, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Humans, MESH: Genome, Transcriptomics, Gene, MESH: Humans, Sequence Analysis, RNA, Gene Expression Profiling, MESH: Nitroimidazoles, Gene Expression Regulation, Bacterial, biology.organism_classification, medicine.disease, MESH: Antitubercular Agents, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 030104 developmental biology, chemistry, Infectious disease (medical specialty), Pretomanid
Abstract: International audience; Tuberculosis (TB) is the most deadly infectious disease worldwide. To reduce TB incidence and counter the spread of multidrug resistant TB, the discovery and characterization of new drugs is essential. In this study, the transcriptional response of two Mycobacterium tuberculosis strains to a pressure of the recently approved dela-manid is investigated. Total RNA sequencing revealed that the response to this bicyclic nitroimidazole shows many similarities with pretomanid, an anti-tuberculous drug from the same class. Although delamanid is found to inhibit cell wall synthesis, the expression of genes involved in this process were only mildly affected. In contrast, a clear parallel was found with components that affect aerobic respiration. This demonstrates that, besides the inhibition of cell wall synthesis, respiratory poisoning plays a fundamental role in the bactericidal effect of delamanid. Remarkably, the most highly induced genes comprise poorly characterized genes for which functional characterization might hint to the target molecule(s) of delamanid and its exact mode(s) of action.
Published: 2019
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124. Comparative assessment of long-read error correction software applied to Nanopore RNA-sequencing data

Author: Rayan Chikhi, Benjamin Istace, Corinne Da Silva, Camille Marchet, Leandro Lima, Jean-Marc Aury, Ségolène Caboche, Hélène Touzet, Equipe de recherche européenne en algorithmique et biologie formelle et expérimentale (ERABLE), Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Roma Tor Vergata [Roma], Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Bioinformatics and Sequence Analysis (BONSAI), Université de Lille, Sciences et Technologies-Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), This work was supported by the French National Research Agency [ANR ASTER, ANR-16-CE23-0001], the INCEPTION project [PIA/ANR-16-CONV-0005], and the Brazilian Ministry of Science, Technology and Innovation (in Portuguese, Ministério da Ciência, Tecnologia e Inovação—MCTI) through the National Counsel of Technological and Scientific Development (in Portuguese, Conselho Nacional de Desenvolvimento Científico e Tecnológico—CNPq), under the Science Without Borders (in Portuguese, Ciências Sem Fronteiras) scholarship grant [process number 203362/2014-4 to L.L.].All authors are part of the ASTER project (ANR ASTER) with the purpose of developing algorithms and software for analysing third-generation sequencing data., The authors thank the ASTER consortium, in particular Camille Sessegolo and Vincent Lacroix, for fruitful discussions. L.L. acknowledges CNPq/Brazil for the support. This work was performed using the computing facilities of the CC LBBE/PRABI and the France Génomique e-infrastructure (ANR-10-INBS-09-08), ANR-19-P3IA-0001,PRAIRIE,PaRis Artificial Intelligence Research InstitutE(2019), ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), ANR-18-CE45-0020,Transipedia,Signatures transcriptionnelles pour une analyse RNA-seq globale(2018), ANR-16-CE23-0001,ASTER,Algorithmes et outils logiciels pour le séquençage d'ARN de troisième génération(2016), Chikhi, Rayan, PaRis Artificial Intelligence Research InstitutE - - PRAIRIE2019 - ANR-19-P3IA-0001 - P3IA - VALID, Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs - - INCEPTION2016 - ANR-16-CONV-0005 - CONV - VALID, APPEL À PROJETS GÉNÉRIQUE 2018 - Signatures transcriptionnelles pour une analyse RNA-seq globale - - Transipedia2018 - ANR-18-CE45-0020 - AAPG2018 - VALID, Algorithmes et outils logiciels pour le séquençage d'ARN de troisième génération - - ASTER2016 - ANR-16-CE23-0001 - AAPG2016 - VALID, Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre National de la Recherche Scientifique (CNRS)-Centre de Recherche en Informatique, Signal et Automatique de Lille - UMR 9189 (CRIStAL), and Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Sciences et Technologies-Inria Lille - Nord Europe
Subjects: Nanopore, Computer science, Analyser, RNA-sequencing, Context (language use), Long reads, computer.software_genre, Benchmark, 03 medical and health sciences, Nanopores, Open Reading Frames, 0302 clinical medicine, Software, Error correction, Molecular Biology, 030304 developmental biology, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], 0303 health sciences, business.industry, Sequence Analysis, RNA, Benchmarking, Exons, Identification (information), Benchmark (computing), Data mining, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Error detection and correction, business, computer, 030217 neurology & neurosurgery, Information Systems
Abstract: Motivation Nanopore long-read sequencing technology offers promising alternatives to high-throughput short read sequencing, especially in the context of RNA-sequencing. However this technology is currently hindered by high error rates in the output data that affect analyses such as the identification of isoforms, exon boundaries, open reading frames and creation of gene catalogues. Due to the novelty of such data, computational methods are still actively being developed and options for the error correction of Nanopore RNA-sequencing long reads remain limited. Results In this article, we evaluate the extent to which existing long-read DNA error correction methods are capable of correcting cDNA Nanopore reads. We provide an automatic and extensive benchmark tool that not only reports classical error correction metrics but also the effect of correction on gene families, isoform diversity, bias toward the major isoform and splice site detection. We find that long read error correction tools that were originally developed for DNA are also suitable for the correction of Nanopore RNA-sequencing data, especially in terms of increasing base pair accuracy. Yet investigators should be warned that the correction process perturbs gene family sizes and isoform diversity. This work provides guidelines on which (or whether) error correction tools should be used, depending on the application type. Benchmarking software https://gitlab.com/leoisl/LR_EC_analyser
Published: 2019
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125. Low CCR5 expression protects HIV-specific CD4+ T cells of elite controllers from viral entry

Author: Mathieu Claireaux, Rémy Robinot, Jérôme Kervevan, Mandar Patgaonkar, Isabelle Staropoli, Anne Brelot, Alexandre Nouël, Stacy Gellenoncourt, Xian Tang, Mélanie Héry, Stevenn Volant, Emeline Perthame, Véronique Avettand-Fenoël, Julian Buchrieser, Thomas Cokelaer, Christiane Bouchier, Laurence Ma, Faroudy Boufassa, Samia Hendou, Valentina Libri, Milena Hasan, David Zucman, Pierre de Truchis, Olivier Schwartz, Olivier Lambotte, Lisa A. Chakrabarti, Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Laboratoire de Microbiologie Clinique [AP-HP Hôpital Necker-Enfants Malades], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biomics (plateforme technologique), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Cytometrie et Biomarqueurs – Cytometry and Biomarkers (UTechS CB), Hôpital Foch [Suresnes], Hôpital Raymond Poincaré [AP-HP], Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Université Paris-Sud - Paris 11 (UP11), This work was supported by grants to L.A.C. from ANRS (17218 and 19206), Institut Pasteur (PasteurInnov TETRHIS), and ANR (14 CE 16002901). The Biomics Platform is a member of the 'France Génomique' consortium (ANR10-INBS-09-08). M.C. was the recipient of a Sidaction fellowship, R.R. of a Pasteur Carnot MS and a Sidaction fellowships, M.P. of an ANRS fellowship, and S.G. of a MESR/Université de Paris fellowship., We are grateful to patients who participated in the study. We thank the investigators of the ANRS CO21 CODEX cohort and Camille Lecuroux for help with recruitment of controller patients, Morgane Marcou and Katia Bourdic for help with recruitment of treated patients, Bernard Lagane for the gift of plamids, and Sophie Novault from the Pasteur CB UTechS for advice on cell sorting. MHC class II tetramer reagents were provided by the NIH Tetramer Core facility at Emory University. The following reagent was obtained through the NIH AIDS Reagent Program, Division of AIDS, NIAID, NIH: HIV-1 PTE Gag peptide set (Cat # 11554)., ANR-14-CE16-0029,PD1VAX,Une nouvelle stratégie de vaccination par vecteur ADN PD1 pour mimer les réponses spécifiques de Gag trouvées chez les contrôleurs spontanés du VIH(2014), and ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010)
Subjects: CD4-Positive T-Lymphocytes, Viral membrane fusion, MESH: Mutation, Receptors, CXCR3, Receptors, CCR5, Science, MESH: Virus Internalization, viruses, General Physics and Astronomy, Down-Regulation, Gene Products, gag, HIV Infections, MESH: Receptors, CCR5, MESH: Down-Regulation, General Biochemistry, Genetics and Molecular Biology, Article, MESH: Receptors, CXCR3, MESH: HIV-1, MESH: Elite Controllers, Humans, MESH: Humans, Multidisciplinary, Retrovirus, Histocompatibility Antigens Class II, MESH: CD4-Positive T-Lymphocytes, virus diseases, MESH: HIV Infections, General Chemistry, Virus Internalization, MESH: Chemokines, MESH: Gene Expression Regulation, Gene Expression Regulation, MESH: Gene Products, gag, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Mutation, MESH: Histocompatibility Antigens Class II, HIV-1, Chemokines, Elite Controllers
Abstract: HIV elite controllers maintain a population of CD4 + T cells endowed with high avidity for Gag antigens and potent effector functions. How these HIV-specific cells avoid infection and depletion upon encounter with the virus remains incompletely understood. Ex vivo characterization of single Gag-specific CD4 + T cells reveals an advanced Th1 differentiation pattern in controllers, except for the CCR5 marker, which is downregulated compared to specific cells of treated patients. Accordingly, controller specific CD4 + T cells show decreased susceptibility to CCR5-dependent HIV entry. Two controllers carried biallelic mutations impairing CCR5 surface expression, indicating that in rare cases CCR5 downregulation can have a direct genetic cause. Increased expression of β-chemokine ligands upon high-avidity antigen/TCR interactions contributes to autocrine CCR5 downregulation in controllers without CCR5 mutations. These findings suggest that genetic and functional regulation of the primary HIV coreceptor CCR5 play a key role in promoting natural HIV control., Here, Claireaux et al. show that people who naturally control HIV infection express lower levels of the viral co-receptor CCR5 in specific CD4+ T cells, and that this results from mutations or receptor internalization by CD4+ T cell-produced chemokines.
Published: 2019
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126. DNA minicircles clarify the specific role of DNA structure on retroviral integration

Author: Anna Juchet, Marc Ruff, Marc Lavigne, Damien Mornico, Christiane Bouchier, Marco Pasi, Stevenn Volant, Richard Lavery, Julien Batisse, Vincent Parissi, Bases moléculaires et structurales des systèmes infectieux (BMSSI), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Virologie moléculaire et Vaccinologie, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génomique (Plate-Forme) - Genomics Platform, Institut Pasteur [Paris], Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), ANRS [AO2014-02 to V.P., M.L.] and [AO2012-02 toM.R. and J.B.], SIDACTION [AI25-1-02332 to M.P., A.J.,M.R., R.L., M.L.] and to M.R. and J.B., ANR, Genomics Platform, member of ‘France Génomique’ consortium [ANR10-INBS-09-08 to C.B.], French Infrastructurefor Integrated Structural Biology [FRISBI, ANR-10-INSB-05-01 to M.R., J.B.], INSTRUCT, part of the European Strategy Forum on Research Infrastructure (ESFRI) sup-ported by national members subscription (to M.R., J.B.).Funding for open access charge: ANRS [A02014-02], ANR-10-INBS-0005,FRISBI,Infrastructure Française pour la Biologie Structurale Intégrée(2010), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), Lavigne, Marc, Infrastructure Française pour la Biologie Structurale Intégrée - - FRISBI2010 - ANR-10-INBS-0005 - INBS - VALID, Organisation et montée en puissance d'une Infrastructure Nationale de Génomique - - France-Génomique2010 - ANR-10-INBS-0009 - INBS - VALID, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), and Microbiologie Fondamentale et Pathogénicité (MFP)
Subjects: Models, Molecular, 0301 basic medicine, [SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Virus Integration, HIV Integrase, Computational biology, Minicircle, 03 medical and health sciences, chemistry.chemical_compound, Genetics, Humans, Nucleosome, Genomic library, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Gene Library, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], biology, Nucleic Acid Enzymes, Nucleosomes, Integrase, Chromatin, Retroviridae, 030104 developmental biology, Histone, chemistry, DNA, Viral, HIV-1, biology.protein, Intercellular Signaling Peptides and Proteins, Nucleic Acid Conformation, DNA, Circular, DNA
Abstract: International audience; Chromatin regulates the selectivity of retroviral integration into the genome of infected cells. At the nucleosome level, both histones and DNA structure are involved in this regulation. We propose a strategy that allows to specifically study a single factor: the DNA distortion induced by the nucleosome. This strategy relies on mimicking this distortion using DNA minicircles (MCs) having a fixed rotational orientation of DNA curvature, coupled with atomic-resolution modeling. Contrasting MCs with linear DNA fragments having identical sequences enabled us to analyze the impact of DNA distortion on the efficiency and selectivity of integration. We observed a global enhancement of HIV-1 integration in MCs and an enrichment of integration sites in the outward-facing DNA major grooves. Both of these changes are favored by LEDGF/p75, revealing a new, histone-independent role of this integration cofactor. PFV integration is also enhanced in MCs, but is not associated with a periodic redistribution of integration sites, thus highlighting its distinct catalytic properties. MCs help to separate the roles of target DNA structure, histone modifications and integrase (IN) cofactors during retroviral integration and to reveal IN-specific regulation mechanisms.
Published: 2016
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127. SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues

Author: Alex K. Shalek, Kun Zhang, Christopher W. Peterson, Orit Rosen, Alison Yu, Robert Lafyatis, Samuel W. Kazer, Oliver Eickelberg, Sarah A. Teichmann, Mauricio Rojas, Martijn C. Nawijn, Colin D. Bingle, Thu Elizabeth Duong, Manuel Garber, Magali Plaisant, Philana Ling Lin, Christine S. Falk, Jennifer P. Wang, Xin Sun, Hengqi Betty Zheng, G. James Gatter, Sarah K. Nyquist, Malte Kühnemund, Joachim L. Schultze, Mark A. Krasnow, Maarten van den Berge, Yan Xu, Samuel J. Allon, Daniel F. Dwyer, Peter Horvath, Benjamin Doran, Brian M. Lin, Herbert B. Schiller, Blake M. Hauser, Fabian J. Theis, Avrum Spira, Paul A. Reyfman, Hans-Peter Kiem, Shaina L. Carroll, Zhiru Guo, Douglas P. Shepherd, Michael von Papen, Ian M. Mbano, Michael Farzan, Daniel Lingwood, JoAnne L. Flynn, Christoph Muus, Dana Pe'er, Stephen R. Quake, Travis K. Hughes, Sarah M. Fortune, Sten Linnarson, Chase J. Taylor, Tanya M. Laidlaw, Emma L. Rawlins, Bonnie Berger, Ashraf S. Yousif, Joakim Lundeberg, Jeffrey A. Whitsett, Ian A. Glass, Delphine Gras, Max A. Seibold, Jay Rajagopal, Jared Feldman, Victor Tkachev, Benjamin E. Mead, Joseph E. Powell, Aviv Regev, Alasdair Leslie, Robert W. Finberg, Yuming Cao, Jennifer M.S. Sucre, Marko Vukovic, Scott B. Snapper, Vincent N. Miao, Naftali Kaminski, Laure-Emmanuelle Zaragosi, Caylin G. Winchell, Faith Taliaferro, Marko Nikolic, Ilias Angelidis, Leslie S. Kean, Lucrezia Colonna, Kathleen M. Buchheit, Aaron G. Schmidt, Ramnik J. Xavier, Tushar J. Desai, Marc H. Wadsworth, Joshua A. Boyce, Alexander M. Tsankov, Nora A. Barrett, Pascal Barbry, Muzlifah Haniffa, Heiko Adler, Alvis Brazma, Hannah P. Gideon, Meshal Ansari, Jason R. Spence, Avinash Waghray, Constantine N. Tzouanas, Jose Ordovas-Montanes, Jonathan A. Kropski, Nicholas E. Banovich, Purushothama Rao Tata, Kerstin B. Meyer, Christos Samakovlis, Haeock Lee, Carly G. K. Ziegler, Alexander V. Misharin, Deborah T. Hung, Sylvie Leroy, Julia Bals, Vanessa Mitsialis, Kourosh Saeb-Parsy, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre National de la Recherche Scientifique (CNRS), FRM (DEQ20180339158), National Infrastructure France Génomique (Commissariat aux Grands Investissements, ANR-10-INBS-09-03, ANR-10-INBS-09-02), ANR-19-P3IA-0002,3IA@cote d'azur,3IA Côte d'Azur(2019), European Project: 874656,discovAIR, Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory, Koch Institute for Integrative Cancer Research at MIT, and Groningen Research Institute for Asthma and COPD (GRIAC)
Subjects: Interferon Type I/immunology, Pneumonia, Viral/virology, Viral/virology, [SDV]Life Sciences [q-bio], ACE2, HIV Infections, non-human primate, HIV Infections/immunology, Mice, 0302 clinical medicine, Single-cell analysis, Alveolar Epithelial Cells/immunology, Interferon, Influenza, Human/immunology, Receptors, Child, Lung, Cells, Cultured, Virus/genetics, 0303 health sciences, Cultured, Serine Endopeptidases, Human/immunology, interferon, Nasal Mucosa/cytology, respiratory system, 3. Good health, Cell biology, Up-Regulation, Interferon Type I, Receptors, Virus, Angiotensin-Converting Enzyme 2, Goblet Cells, Enterocytes/immunology, Single-Cell Analysis, Coronavirus Infections, hormones, hormone substitutes, and hormone antagonists, medicine.drug, Proteases, Coronavirus Infections/virology, Adolescent, Cells, Pneumonia, Viral, Receptors, Virus/genetics, Peptidyl-Dipeptidase A/genetics, Lung injury, Biology, Peptidyl-Dipeptidase A, TMPRSS2, General Biochemistry, Genetics and Molecular Biology, Article, Cell Line, ISG, 03 medical and health sciences, Betacoronavirus, Serine Endopeptidases/metabolism, Downregulation and upregulation, Lung/cytology, Influenza, Human, scRNA-seq, medicine, Ace2, Covid-19, Isg, Sars-cov-2, Human, Influenza, Mouse, Non-human Primate, Scrna-seq, Tuberculosis, Animals, Humans, human, Pandemics, Tuberculosis/immunology, mouse, 030304 developmental biology, Innate immune system, SARS-CoV-2, Betacoronavirus/physiology, Interferon-stimulated gene, COVID-19, Mycobacterium tuberculosis, Pneumonia, Macaca mulatta, respiratory tract diseases, Nasal Mucosa, Enterocytes, Goblet Cells/immunology, Alveolar Epithelial Cells, 030217 neurology & neurosurgery
Abstract: Summary There is pressing urgency to understand the pathogenesis of the severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2), which causes the disease COVID-19. SARS-CoV-2 spike (S) protein binds angiotensin-converting enzyme 2 (ACE2), and in concert with host proteases, principally transmembrane serine protease 2 (TMPRSS2), promotes cellular entry. The cell subsets targeted by SARS-CoV-2 in host tissues and the factors that regulate ACE2 expression remain unknown. Here, we leverage human, non-human primate, and mouse single-cell RNA-sequencing (scRNA-seq) datasets across health and disease to uncover putative targets of SARS-CoV-2 among tissue-resident cell subsets. We identify ACE2 and TMPRSS2 co-expressing cells within lung type II pneumocytes, ileal absorptive enterocytes, and nasal goblet secretory cells. Strikingly, we discovered that ACE2 is a human interferon-stimulated gene (ISG) in vitro using airway epithelial cells and extend our findings to in vivo viral infections. Our data suggest that SARS-CoV-2 could exploit species-specific interferon-driven upregulation of ACE2, a tissue-protective mediator during lung injury, to enhance infection., Graphical Abstract, Highlights • Meta-analysis of human, non-human primate, and mouse single-cell RNA-seq datasets for putative SARS-CoV-2 targets • Type II pneumocytes, nasal secretory cells, and absorptive enterocytes are ACE2 + TMPRSS2 + • Interferon and influenza increase ACE2 in human nasal epithelia and lung tissue • Mouse Ace2 is not upregulated by interferon, raising implications for disease modeling, Analysis of single-cell RNA-seq datasets from human, non-human primate, and mouse barrier tissues identifies putative cellular targets of SARS-CoV-2 on the basis of ACE2 and TMPRSS2 expression. ACE2 represents a previously unappreciated interferon-stimulated gene in human, but not mouse, epithelial tissues, identifying anti-viral induction of a host tissue-protective mechanism, but also a potential means for viral exploitation of the host response.
Published: 2020
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128. Familial breast cancer and DNA repair genes: Insights into known and novel susceptibility genes from the GENESIS study, and implications for multigene panel testing

Author: Girard, Elodie, Eon-Marchais, Séverine, Olaso, François, Renault, Anne, Damiola, Francesca, Dondon, Marie-Gabrielle, Barjhoux, Laure, Goidin, Didier, Meyer, François, Le Gal, Dorothée, Beauvallet, Juana, Mebirouk, Noura, Lonjou, Christine, Coignard, Julie, Marcou, Morgane, Cavaciuti, Eve, Baulard, François, Bihoreau, François, Cohen-Haguenauer, Odile, Leroux, Dominique, Penet, Jean, Fert-Ferrer, Sandra, Colas, Chrystelle, Frebourg, Thierry, Eisinger, François, Adenis, Claude, Fajac, Anne, Gladieff, Laurence, Tinat, Julie, Floquet, Anne, Chiesa, Jean, Giraud, Sophie, Mortemousque, Isabelle, Soubrier, Florent, Audebert-Bellanger, Séverine, Limacher, Jean-Marc, Lasset, Christine, Lejeune-Dumoulin, Sophie, Dreyfus, Catherine, Bignon, Yves-Jean, Longy, Michel, Pujol, Pascal, Venat-Bouvet, Laurence, Bonadona, Valérie, Berthet, Pascaline, Luporsi, Elisabeth, Maugard, Christine, Noguès, Catherine, Delnatte, Capucine, Fricker, Paul, Gesta, Paul, Faivre, Laurence, Lortholary, Alain, Buecher, Bruno, Caron, Olivier, Gauthier-Villars, Marion, Coupier, Isabelle, Servant, Nicolas, Boland, Anne, Mazoyer, Sylvie, Deleuze, Jean-François, Stoppa-Lyonnet, Dominique, Andrieu, Nadine, Lesueur, Fabienne, Université Paris sciences et lettres (PSL), Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Centre Léon Bérard [Lyon]-Hospices Civils de Lyon (HCL), Life Sciences and Diagnostics Group [Les Ulis, France], Agilent Technologies France, Laboratoire Information, Milieux, Médias, Médiations - EA 3820 (I3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université de Toulon (UTLN), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Traitement Algorithmique et Matériel de la Communication, de l'Information et de la Connaissance (TAMCIC), Ecole Nationale Supérieure des Télécommunications de Bretagne-Centre National de la Recherche Scientifique (CNRS), CRLCC Jean Godinot, Centre Hospitalier de Chambéry (C.H.de Chambéry), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Département de Génétique [Institut Curie, Paris] (Unité de Pharmacogénomique), Institut Curie [Paris], Génétique médicale et fonctionnelle du cancer et des maladies neuropsychiatriques, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Claudius Regaud, Service de génétique [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Département d'oncologie médicale, Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Laboratoire de Cytogénétique, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Service de génétique [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Génétique épidémiologique et moléculaire des pathologies cardiovasculaires, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Génétique Moléculaire et d'Histocompatibilité [Brest], Hôpital Morvan [Brest]-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Hôpital pasteur [Colmar], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut Sainte Catherine [Avignon], Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Département de pathologie, Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Hôpital Dupuytren [CHU Limoges], Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Consultation d'Oncogénétique, Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Alexis Vautrin (CAV), Laboratoire de Diagnostic Génétique [CHU Strasbourg], Université de Strasbourg (UNISTRA)-CHU Strasbourg, Laboratoire d'Oncogénétique, CRLCC René Huguenin, CRLCC René Gauducheau, Service d'Oncologie Médicale [Strasbourg] (UNICANCER Centre Paul Strauss), Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC), Centre Hospitalier Georges Renon [Niort] (CH Georges Renon Niort), Génétique des Anomalies du Développement (GAD), Université de Bourgogne (UB)-IFR100 - Structure fédérative de recherche Santé-STIC, Centre Catherine-de-Sienne [Nantes] (CCS), Service de Génétique Oncologique, Onco-génétique, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Unité d'Oncogénétique, CRLCC Val d'Aurelle - Paul Lamarque, Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Grant sponsor: comprehensive cancer center SiRIC, Grant numbers: INCa-DGOS-4654, Grant sponsor: Fondation ARC pour la recherche sur le cancer, Grant numbers: PJA 20151203365, Grant sponsor: France Génomique National infrastructure, Grant numbers: ANR-10-INBS-09, Grant sponsor: Institut National du Cancer (INCa), Grant numbers: b2008-029/LL-LC, Grant sponsor: Ligue Comité de Paris, Grant numbers: RS15/75-78, Grant sponsor: Ligue Nationale Contre le Cancer, Grant numbers: PRE05/DSL PRE07/DSL PRE11/NA., Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Cancer et génôme: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, MINES ParisTech - École nationale supérieure des mines de Paris-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de génétique et de physiologie moléculaire et cellulaire (CGPhiMC), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Epidémiologie des cancers : Radiocarcinogénèse et effets iatrogènes des traitements, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), E06, Centre de Recherche en Cancérologie de Lyon (CRCL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Centre Léon Bérard [Lyon]-Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Plateforme Post-génomique de la Pitié-Salpêtrière (P3S), UMS omique (OMIQUE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), CRESS, Université de Franche-Comté (UFC), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Service de génétique médicale CHU Grenoble Hôpital Couple Enfant, CHU Grenoble, CHU Saint-Antoine [APHP], Génétique du cancer et des maladies neuropsychiatriques (GMFC), Centre oscar lambert, service d'hématologie chu, CHU Tenon [APHP], CRLCC Institut Claudius Regaud, Centre Beninois pour l'Environnement et le développement économique et Social (CEBEDES), Service de Génétique Clinique [CHRU Nïmes], Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP], Service de Pédiatrie et de Génétique Médicale, Hôpital Jeanne de Flandre [Lille], Imagerie Moléculaire et Stratégies Théranostiques - Clermont Auvergne (IMoST), Université Clermont Auvergne (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Jean Perrin, CRLCC Jean Perrin, Institut Bergonié - CRLCC Bordeaux, Service d'Oncologie médicale [CHU Limoges], CHU Limoges, Génétique épidémiologique et structures des populations humaines (Inserm U535), Epidémiologie, sciences sociales, santé publique (IFR 69), Université Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Régional de Lutte contre le Cancer François Baclesse (CRLC François Baclesse ), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Laboratoire de diagnostic génétique, Hôpital Universitaire de Strasbourg, Strasbourg, Centre René Gauducheau, Genetic and Immunology Medical Institute (GIMI), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL)-Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL), Fédération Francophone de la Cancérologie Digestive, FFCD, Institut Gustave Roussy (IGR), Service d'oncogénétique, Institut Curie, Service de génétique médicale [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Equipe 6, Université Paris Descartes - Paris 5 (UPD5), Méthodologie statistique et épidémiologie génétique des maladies multifactorielles, Institut National de la Santé et de la Recherche Médicale (INSERM), Section Génétique - Groupe Prédispositions génétiques au cancer, Centre International de Recherche contre le Cancer (CIRC), MINES ParisTech - École nationale supérieure des mines de Paris, Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Nice Sophia Antipolis (... - 2019) (UNS), Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure des Télécommunications de Bretagne, Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Lille Nord de France (COMUE)-UNICANCER, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Andrieu, Nadine, Institut Curie [Paris]-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)
Subjects: Adult, DNA Repair, case-control study, [SDV]Life Sciences [q-bio], Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.GEN] Life Sciences [q-bio]/Genetics, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Risk Assessment, Cancer Genetics and Epigenetics, breast cancer, multigene panel testing, [SDV.CAN] Life Sciences [q-bio]/Cancer, Humans, Genetic Predisposition to Disease, Genetic Testing, Aged, Aged, 80 and over, [SDV.GEN]Life Sciences [q-bio]/Genetics, Siblings, case–control study, Middle Aged, [SDV] Life Sciences [q-bio], variant, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Case-Control Studies, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, exome sequencing
Abstract: Pathogenic variants in BRCA1 and BRCA2 only explain the underlying genetic cause of about 10% of hereditary breast and ovarian cancer families. Because of cost‐effectiveness, multigene panel testing is often performed even if the clinical utility of testing most of the genes remains questionable. The purpose of our study was to assess the contribution of rare, deleterious‐predicted variants in DNA repair genes in familial breast cancer (BC) in a well‐characterized and homogeneous population. We analyzed 113 DNA repair genes selected from either an exome sequencing or a candidate gene approach in the GENESIS study, which includes familial BC cases with no BRCA1 or BRCA2 mutation and having a sister with BC (N = 1,207), and general population controls (N = 1,199). Sequencing data were filtered for rare loss‐of‐function variants (LoF) and likely deleterious missense variants (MV). We confirmed associations between LoF and MV in PALB2, ATM and CHEK2 and BC occurrence. We also identified for the first time associations between FANCI, MAST1, POLH and RTEL1 and BC susceptibility. Unlike other associated genes, carriers of an ATM LoF had a significantly higher risk of developing BC than carriers of an ATM MV (ORLoF = 17.4 vs. ORMV = 1.6; p Het = 0.002). Hence, our approach allowed us to specify BC relative risks associated with deleterious‐predicted variants in PALB2, ATM and CHEK2 and to add MAST1, POLH, RTEL1 and FANCI to the list of DNA repair genes possibly involved in BC susceptibility. We also highlight that different types of variants within the same gene can lead to different risk estimates., What's new? Pathogenic variants in BRCA1 and BRCA2 only explain the genetic cause of about 10% of hereditary breast and ovarian cancer families, and the clinical usefulness of testing other genes following the recent introduction of cost‐effective multigene panel sequencing in diagnostics laboratories remains questionable. This large case‐control study describes genetic variation in 113 DNA repair genes and specifies breast cancer relative risks associated with rare deleterious‐predicted variants in PALB2, ATM, and CHEK2. Importantly, different types of variants within the same gene can lead to different risk estimates. The results may help improve risk prediction models and define gene‐specific consensus management guidelines.
Published: 2019
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129. A single droplet digital PCR for ESR1 activating mutations detection in plasma

Author: Charlotte Proudhon, Samia Melaabi, Ivan Bièche, Marc Michel, Emmanuelle Jeannot, Lauren Darrigues, Radouane El Ayachy, Marc-Henri Stern, Camille Benoist, Jean-Yves Pierga, Nicolas Epaillard, Aurelien Noret, Anne Vincent-Salomon, Aurore Rampanou, Luc Cabel, François-Clément Bidard, CIC1428 IGR-CURIE, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie [Paris], Unité de génétique et biologie des cancers (U830), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Equipex: ANR-10-INBS-09–08 Agence Nationale de la Recherche, ANR Institut National Du Cancer, INCa: SiRIC 2 Curie - grant INCa-DGOS-INSERM_12554 Institut Curie: ANR-10-EQPX-03 Innovative Medicines Initiative, IMI: 115749, Acknowledgements We would like to thank members of the Circulating Tumor Biomarkers laboratory for helpful discussions and especially Amanda Silveira for critical reading of the manuscript. High-throughput sequencing has been performed by the ICGex NGS platform of the Institut Curie supported by the grants ANR-10-EQPX-03 (Equipex) and ANR-10-INBS-09–08 (France Génomique Consortium) from the Agence Nationale de la Recherche ('Investissements d’Avenir' program), by the Canceropole Ile-de-France and by the SiRIC 2 Curie program - SiRIC Grant « INCa-DGOS-Inserm_12554 »., Funding SIRIC 2 Curie (grant INCa-DGOS-Inserm_12554) and the Innovative Medicines Initiative Joint Undertaking under grant agreement no. 115749 (project Cancer-ID). The funding sources of the study had no role in the design of the study, collection, analysis, or interpretation of the data or in the writing of this report., and HAL UVSQ, Équipe
Subjects: 0301 basic medicine, Cancer Research, Pyridines, [SDV]Life Sciences [q-bio], Estrogen receptor, ddPCR, medicine.disease_cause, Polymerase Chain Reaction, Piperazines, Exon, Plasma, 0302 clinical medicine, Gene Frequency, Digital polymerase chain reaction, Multiplex, Prospective Studies, Aromatase, Fulvestrant, circulating tumor DNA, 0303 health sciences, biology, Exons, 3. Good health, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, Female, KRAS, medicine.drug_class, Breast Neoplasms, 03 medical and health sciences, breast cancer, Growth factor receptor, medicine, Genetics, Humans, Liquid biopsy, Molecular Biology, Gene, 030304 developmental biology, Aromatase inhibitor, Estrogen Receptor alpha, Molecular biology, ESR1 mutation, body regions, monitoring, 030104 developmental biology, Mutation, Cancer research, biology.protein, Estrogen receptor alpha
Abstract: BackgroundActivating mutations in the estrogen receptor 1 (ESR1) gene are recurrent mechanisms of acquired resistance to aromatase inhibitors (AI), and may be the target of other selective estrogen receptor down-regulators. To assess the clinical utility of monitoring ESR1 resistant mutations, a droplet digital PCR (ddPCR)-based assay compatible with body fluids is ideal due to its cost-effectiveness and quick turnaround.MethodsWe designed a multiplex ddPCR, which combines a drop-off assay, targeting the clustered hotspot mutations found in exon 8, with another pair of probes interrogating the E380Q mutation in exon 5. We assessed its sensitivity in vitro using synthetic oligonucleotides, harboring E380Q, L536R, Y537C, Y537N, Y537S or D538G mutations. Validation of the assay was performed on plasma samples from a prospective study and compared to next generation sequencing (NGS) data.ResultsThe multiplex ESR1-ddPCR showed a high sensitivity with a limit of detection ranging from 0.07 to 0.19% in mutant allele frequency depending on the mutation tested. The screening of plasma samples from patients with AI-resistant metastatic breast cancer identified ESR1 mutations in 29% of them with perfect concordance (and higher sensitivity) to NGS data obtained in parallel. Additionally, this test identifies patients harboring polyclonal alterations. Furthermore, the monitoring of ctDNA using this technique during treatment follow-up predicts the radiological response to palbociclib-fulvestrant.ConclusionThe multiplex ESR1-ddPCR detects, in a single reaction, the most frequent ESR1 activating mutations and is compatible with plasma samples. This method is thus suitable for real-time ESR1 mutation monitoring in large cohorts of patients.Statement of translational relevanceExons 5 and 8 mutations in ESR1 are recurrent mechanisms of resistance to aromatase inhibitors (AI) in estrogen receptor (ER)-positive metastatic breast cancer and may be targeted by selective ER down-regulators. We implemented a novel droplet digital PCR, which allows for the detection of the most frequent ESR1 mutations in circulating cell-free DNA. In prospectively collected plasma samples, ESR1 mutations were found in 29% of AI-resistant patients, with excellent concordance and higher sensitivity to next generation sequencing. Moreover, circulating ESR1 mutations appear to be reliable markers for ctDNA monitoring in order to predict treatment response. Ultimately, the short turnaround time, high sensitivity and limited cost of the ESR1-ddPCR are compatible with repeated samplings to detect the onset of resistance to AI before the radiological progression. This opens a window of opportunity to develop new clinical strategies for breast cancer hormone therapy, as tested in an ongoing phase 3 trial.List of abbreviationsAIAromatase InhibitorcfDNACell-free DNActDNACirculating tumor DNAddPCRDroplet digital PCRER+ HER2-MBCER+ HER2-negative Metastatic Breast CancerEREstrogen ReceptorER+Estrogen Receptor positiveLOBLimit of blankLODLimit of detectionMAFMutant Allele FrequencyPBMCPeripheral blood mononuclear cellsPDProgressive diseaseSDStandard deviationToPTime of progressionWTWild typeHuman genesESR1: Estrogen Receptor 1HER2: Human Epidermal Growth Factor Receptor 2EGFR: Epithelial Growth Factor ReceptorKRAS: KRAS proto-oncogene, GTPaseBRAF: B-Raf Proto-Oncogene, Serine/Threonine kinase
Published: 2019
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130. Genomic insights into the 2016–2017 cholera epidemic in Yemen

Author: Dhirendra Kumar, Abdullah M. Assiri, Naresh Chand Sharma, Joseph F. Wamala, Samuel Kariuki, Caroline Seguin, Thérèse E. Malliavin, Abdullrahman A. Almesbahi, Nicholas R. Thomson, Samuel M. C. Njoroge, Thandavarayan Ramamurthy, Mona Naji, Daryl Domman, Elisabeth Njamkepo, Samar Saeed Nasher, Jane Y. Carter, Abdinasir Abubakar, Bita Bakhshi, Jean Rauzier, Andrew S. Azman, Christiane Bouchier, John Kiiru, Francisco J. Luquero, François-Xavier Weill, Hayder H.N. Abulmaali, Marie Laure Quilici, Mohammad Reza Pourshafie, Ankur Rakesh, Mamunur Rahman Malik, Bactéries pathogènes entériques (BPE), Institut Pasteur [Paris] (IP), The Wellcome Trust Sanger Institute [Cambridge], Los Alamos National Laboratory (LANL), Ministry of Public Health [Yemen], Epicentre [Paris] [Médecins Sans Frontières], Ministry of Health [Saudi Arabia], Kenya Medical Research Institute (KEMRI), Institut Pasteur d'Iran, Réseau International des Instituts Pasteur (RIIP), WHO - Regional Office for the Eastern Mediterranean [Cairo, Egypt] (EMRO), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Amref Health Africa [Kenya], African Medical and Research Foundation (AMREF), Médecins Sans Frontières [Dubai], Génomique (Plate-Forme) - Genomics Platform, Bioinformatique structurale - Structural Bioinformatics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Tarbiat Modares University [Tehran], Ministry of Health [Iraq], Maharishi Valmiki Hospital, Translational Health Science and Technology Institute [Faridabad] (THSTI), Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), London School of Hygiene and Tropical Medicine (LSHTM), This study was supported by the Institut Pasteur, Santé publique France, the French government’s Investissement d’Avenir programme, Laboratoire d’Excellence ‘Integrative Biology of Emerging Infectious Diseases’ (grant number ANR-10-LABX-62-IBEID), the Wellcome Trust through grant 098051 to the Sanger Institute and the Department of Biotechnology of India. The Institut Pasteur Genomics Platform is a member of the France Génomique consortium (ANR10-INBS-09-08)., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), Institut Pasteur [Paris], Regional Office for the Eastern Mediterranean [Cairo] (EMRO), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Serotype, Yemen, 030106 microbiology, Context (language use), Biology, medicine.disease_cause, El Tor, 03 medical and health sciences, Antibiotic resistance, Cholera, Pandemic, medicine, Humans, Vibrio cholerae, Phylogeny, Multidisciplinary, Outbreak, Genomics, biology.organism_classification, medicine.disease, Virology, 3. Good health, 030104 developmental biology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Genome, Bacterial
Abstract: International audience; Yemen is currently experiencing, to our knowledge, the largest cholera epidemic in recent history. The first cases were declared in September 2016, and over 1.1 million cases and 2,300 deaths have since been reported1. Here we investigate the phylogenetic relationships, pathogenesis and determinants of antimicrobial resistance by sequencing the genomes of Vibrio cholerae isolates from the epidemic in Yemen and recent isolates from neighbouring regions. These 116 genomic sequences were placed within the phylogenetic context of a global collection of 1,087 isolates of the seventh pandemic V. cholerae serogroups O1 and O139 biotype El Tor2-4. We show that the isolates from Yemen that were collected during the two epidemiological waves of the epidemic1-the first between 28 September 2016 and 23 April 2017 (25,839 suspected cases) and the second beginning on 24 April 2017 (more than 1 million suspected cases)-are V. cholerae serotype Ogawa isolates from a single sublineage of the seventh pandemic V. cholerae O1 El Tor (7PET) lineage. Using genomic approaches, we link the epidemic in Yemen to global radiations of pandemic V. cholerae and show that this sublineage originated from South Asia and that it caused outbreaks in East Africa before appearing in Yemen. Furthermore, we show that the isolates from Yemen are susceptible to several antibiotics that are commonly used to treat cholera and to polymyxin B, resistance to which is used as a marker of the El Tor biotype.
Published: 2019
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131. Differential dynamics of microbial community networks help identify microorganisms interacting with residue-borne pathogens: the case of Zymoseptoria tritici in wheat

Author: Frédéric Suffert, Lydie Kerdraon, Matthieu Barret, Valérie Laval, BIOlogie et GEstion des Risques en agriculture (BIOGER), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Université Paris Saclay (COmUE), Institut de Recherche en Horticulture et Semences (IRHS), Université d'Angers (UA)-Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), European Union [634179], AgroParisTech-Institut National de la Recherche Agronomique (INRA), and This study was performed in collaboration with the GeTcore facility, Toulouse, France (http://get.genotoul.fr/), supported by France Génomique National Infrastructure, funded as part of the 'Investissement d’avenir programmanage by ANR (contract ANR-10-INBS-09).
Subjects: [SDV.SA]Life Sciences [q-bio]/Agricultural sciences, 0106 biological sciences, Crop residue, Microorganism, [SDV]Life Sciences [q-bio], Ecological network analysis, Biological pest control, 01 natural sciences, Pathosystem, Septoria, Pathogen, Triticum, 2. Zero hunger, 0303 health sciences, Plant Stems, biology, Microbiota, food and beverages, Metabarcoding, Microbial communities, Microbiome, Pathobiome, Septoria tritici blotch, Wheat residues, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Host-Pathogen Interactions, [SDE]Environmental Sciences, lcsh:QR100-130, Microbiology (medical), Microbiology, lcsh:Microbial ecology, 03 medical and health sciences, Microbial ecology, Botany, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, Plant Diseases, 030304 developmental biology, Bacteria, 030306 microbiology, Research, Fungi, 15. Life on land, biology.organism_classification, [SDV.BV.PEP]Life Sciences [q-bio]/Vegetal Biology/Phytopathology and phytopharmacy, Plant Leaves, Microbial population biology, Microbial Interactions, 010606 plant biology & botany
Abstract: BackgroundWheat residues are a crucial determinant of the epidemiology of Septoria tritici blotch, as they support the sexual reproduction of the causal agent Zymoseptoria tritici. We aimed to characterize the effect of infection with this fungal pathogen on the microbial communities present on wheat residues, and to identify microorganisms interacting with it. We used metabarcoding to characterize the microbiome associated with wheat residues placed outdoors, with and without preliminary Z. tritici inoculation, comparing a first set of residues in contact with the soil and a second set without contact with the soil, on four sampling dates in two consecutive years.ResultsThe diversity of the tested conditions, leading to the establishment of different microbial communities according to the origins of the constitutive taxa (plant only, or plant and soil), highlighted the effect of Z. tritici on the wheat residue microbiome. Several microorganisms were affected by Z. tritici infection, even after the disappearance of the pathogen. Linear discriminant analyses and ecological network analyses were combined to describe the communities affected by infection. The number of fungi and bacteria promoted or inhibited by inoculation with Z. tritici decreased over time, and was smaller for residues in contact with the soil. The interactions between the pathogen and other microorganisms appeared to be mostly indirect, despite the strong position of the pathogen as a keystone taxon in networks. Direct interactions with other members of the communities mostly involved fungi, including other wheat pathogens. Our results provide essential information about the alterations to the microbial community in wheat residues induced by the mere presence of a fungal pathogen, and vice versa. Species already described as beneficial or biocontrol agents were found to be affected by pathogen inoculation.ConclusionsThe strategy developed here can be viewed as a proof-of-concept focusing on crop residues as a particularly rich ecological compartment, with a high diversity of fungal and bacterial taxa originating from both the plant and soil compartments, and for Z. tritici-wheat as a model pathosystem. By revealing putative antagonistic interactions, this study paves the way for improving the biological control of residue-borne diseases.
Published: 2019
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132. Non-specific interference of cobalt with siderophore-dependent iron uptake pathways

Author: Bénédicte Pesset, Pamela Saint Auguste, Olivier Cunrath, Dirk Bumann, Odile Sismeiro, Julien Pérard, Quentin Perraud, Isabelle Michaud-Soret, Isabelle J. Schalk, Rachel Legendre, Anne Forster, Pierre Fechter, Ana Carballido Lopez, Jean Yves Coppée, Gaëtan L. A. Mislin, Gwenaëlle Graulier, Hugo Varet, Biotechnologie et signalisation cellulaire (BSC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS), Laboratoire de Chimie et Biologie des Métaux (LCBM - UMR 5249), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Transcriptome et Epigénome (PF2), Institut Pasteur [Paris], Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Focal Area Infection Biology, Biozentrum, University of Basel (Unibas), This work was partly funded by the Centre National de la Recherche Scientifique. O. Cunrath held a fellowship from the French Ministère de la Recherche et de la Technologie (3 years) and the FRM (Fondation pour la Recherche Médicale, 6 months). A. Y. Carballido Lopez held a fellowship from the University of Strasbourg (IDEX) and B. Pesset from the DGA (Direction Générale des l’Armement). J. P. and I. M. S. thank the Laboratory of Excellence GRAL (grant ANR-11-LABX-49-01) and the Labex ARCANE (grant ANR-11-LABX-0003-01). The Transcriptome and Epigenome Platform is a member of the France Génomique consortium (ANR10-NBS-09-08)., We thank Dr A. Boos and P. Ronot (Institut Pluridisciplinaire Hubert Curien, Strasbourg) for their help in the ICP-AES measurements., ANR-11-LABX-0003,ARCANE,Grenoble, une chimie bio-motivée(2011), Biologie des Métaux (BioMet), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Bioinformatique évolutive - Evolutionary Bioinformatics, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Université de Strasbourg (UNISTRA)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Institut Pasteur [Paris] (IP), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, inorganic chemicals, Siderophore, Iron, Biophysics, Down-Regulation, Siderophores, Biochemistry, Models, Biological, Biomaterials, 03 medical and health sciences, chemistry.chemical_compound, Biosynthesis, Bacterial Proteins, Phenols, Operon, medicine, Transcriptional regulation, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Psychological repression, 030102 biochemistry & molecular biology, biology, Chemistry, Metals and Alloys, Transporter, Cobalt, Gene Expression Regulation, Bacterial, biology.organism_classification, Sciences du Vivant [q-bio]/Microbiologie et Parasitologie, Up-Regulation, Thiazoles, 030104 developmental biology, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Chemistry (miscellaneous), Pseudomonas aeruginosa, Ferric, Bacterial outer membrane, Oligopeptides, Bacteria, medicine.drug
Abstract: International audience; Much data shows that biological metals other than Fe3+ can interfere with Fe3+ acquisition by siderophores in bacteria. Siderophores are small Fe3+ chelators produced by the microorganisms to obtain access to Fe3+. Here, we show that Co2+ is imported into Pseudomonas aeruginosa cells in a complex with the siderophore pyochelin (PCH) by the ferri-PCH outer membrane transporter FptA. Moreover, the presence of Co2+ in the bacterial environment strongly affects the production of PCH. Proteomic and transcriptomic approaches showed that a decrease of PCH production is associated with repression of the expression of the genes involved in PCH biosynthesis. We used various molecular biology approaches to show that this repression is not Fur-(ferric uptake transcriptional regulator) dependent but due to competition of PCH-Co with PCH-Fe for PchR (transcriptional activator), thus inhibiting the formation of PchR-PCH-Fe and consequently the expression of the PCH genes. We observed a similar mechanism of repression of PCH production, but to a lesser extent, by Ni2+, but not for Zn2+, Cu2+, or Mn2+. Here, we show, for the first time at a molecular level, how the presence of a contaminant metal can interfere with Fe3+ acquisition by the siderophores PCH and PVD.
Published: 2019
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133. Integrated clinical and omics approach to rare diseases: novel genes and oligogenic inheritance in holoprosencephaly

Author: Kim, A., Savary, C., Dubourg, C., Carre, W., Mouden, C., Hamdi-Roze, H., Guyodo, H., Douce, J. le, Pasquier, L., Flori, E., Gonzales, M., Beneteau, C., Boute, O., Attie-Bitach, T., Roume, J., Goujon, L., Akloul, L., Odent, S., Watrin, E., Dupe, V., Tayrac, M. de, David, V., Genin, E., Campion, D., Dartigues, J.F.C.O., Deleuze, J.F., Lambert, J.C., Redon, R., Ludwig, T., Grenier-Boley, B., Letort, S., Lindenbaum, P., Meyer, V., Quenez, O., Dina, C., Bellenguez, C., Charbonnier-Le Clezio, C., Giemza, J., Chatel, S., Ferec, C., Marec, H. le, Letenneur, L., Nicolas, G., Rouault, K., Bacq, D., Boland, A., Lechner, D., Wijmenga, C., Swertz, M.A., Slagboom, P.E., Ommen, G.J.B. van, Duijn, C.M. van, Boomsma, D.I., Bakker, P.I.W. de, Bovenberg, J.A., Craen, A.J.M. de, Beekman, M., Hofman, A., Willemsen, G., Wolffenbuttel, B., Platteel, M., Y.P. du, Chen, R.Y., Cao, H.Z., Cao, R., Sun, Y.S., Cao, J.S., Dijk, F. van, Neerincx, P.B.T., Deelen, P., Dijkstra, M., Byelas, G., Kanterakis, A., Bot, J., Ye, K., Lameijer, E.W., Vermaat, M., Laros, J.F.J., Dunnen, J.T. den, Knijff, P. de, Karssen, L.C., Leeuwen, E.M. van, Amin, N., Koval, V., Rivadeneira, F., Estrada, K., Hehirkwa, J.Y., Ligt, J. de, Abdellaoui, A., Hottenga, J.J., Kattenberg, V.M., Enckevort, D. van, Mei, H., Santcroos, M., Schaik, B.D.C. van, Handsaker, R.E., McCarroll, S.A., Eichler, E.E., Ko, A., Sudmant, P., Francioli, L.C., Kloosterman, W.P., Nijman, I.J., Guryev, V., FREX Consortium, GoNL Consortium, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Lifestyle Medicine (LM), Nanomedicine & Drug Targeting, Groningen Research Institute for Asthma and COPD (GRIAC), Center for Liver, Digestive and Metabolic Diseases (CLDM), Institut de Génétique et Développement de Rennes (IGDR), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), CHU Pontchaillou [Rennes], Service de génétique et embryologie médicales [CHU Trousseau], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de génétique médicale - Unité de génétique clinique [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), This work was supported by Fondation Maladie Rares (grant PMO1201204), Agence Nationale de la Recherche (grant ANR-12-BSV1-0007-01) and the Agence de la Biomedecine (AMP2016). This work was supported by La Fondation Maladie Rares and the Agence de la Biomedecine. The authors acknowledge the Centre de Ressources Biologiques (CRB)-Santé (http://www.crbsante-rennes.com) of Rennes for managing patient samples. This Work was supported by France Génomique National infrastructure, funded as part of 'Investissement d'avenir' program managed by Agence Nationale pour la Recherche (contrat ANR-10-INBS-09) https://www.france-genomique.org/spip/spip.php?article158. This study makes use of data generated by the Genome of the Netherlands Project. Funding for the project was provided by the Netherlands Organization for Scientific Research under award number 184 021 007, dated July 9, 2009 and made available as a Rainbow Project of the Biobanking and Biomolecular Research Infrastructure Netherlands (BBMRI-NL). Samples where contributed by LifeLines (http://lifelines.nl/lifelines-research/general), The Leiden Longevity Study (http://www.healthy-ageing.nl, ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), APH - Methodology, APH - Mental Health, Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: 0301 basic medicine, Exome/genetics, Male, Multifactorial Inheritance, MOUSE, PHENOTYPE, GUIDELINES, PATHWAY, 0302 clinical medicine, Holoprosencephaly, Locus heterogeneity, SEQUENCE VARIANTS, oligogenic inheritance, Sonic hedgehog, Exome, Exome sequencing, Genetics, 0303 health sciences, Comparative Genomic Hybridization, Oligogenic Inheritance, Phenotype, 3. Good health, Pedigree, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, FAT1, musculoskeletal diseases, EXPRESSION, congenital, hereditary, and neonatal diseases and abnormalities, Holoprosencephaly/genetics, Clinical Neurology, Biology, MICE LACKING, 03 medical and health sciences, sonic hedgehog, Rare Diseases, Rare Diseases/genetics, primary cilia, DEFICIENT, medicine, Humans, Gene, Multifactorial Inheritance/genetics, 030304 developmental biology, [SDV.GEN]Life Sciences [q-bio]/Genetics, IDENTIFICATION, Genetic heterogeneity, MUTATIONS, medicine.disease, 030104 developmental biology, holoprosencephaly, Case-Control Studies, Forebrain, Mutation, biology.protein, Neurology (clinical), 030217 neurology & neurosurgery, exome
Abstract: Kim et al. identify novel genes and disease pathways in the forebrain developmental disorder holoprosencephaly, and show that many cases involve oligogenic inheritance. The findings underline the roles of Sonic Hedgehog and primary cilia in forebrain development, and show that integrating clinical phenotyping into genetic studies can uncover relevant mutations.Holoprosencephaly is a pathology of forebrain development characterized by high phenotypic heterogeneity. The disease presents with various clinical manifestations at the cerebral or facial levels. Several genes have been implicated in holoprosencephaly but its genetic basis remains unclear: different transmission patterns have been described including autosomal dominant, recessive and digenic inheritance. Conventional molecular testing approaches result in a very low diagnostic yield and most cases remain unsolved. In our study, we address the possibility that genetically unsolved cases of holoprosencephaly present an oligogenic origin and result from combined inherited mutations in several genes. Twenty-six unrelated families, for whom no genetic cause of holoprosencephaly could be identified in clinical settings [whole exome sequencing and comparative genomic hybridization (CGH)-array analyses], were reanalysed under the hypothesis of oligogenic inheritance. Standard variant analysis was improved with a gene prioritization strategy based on clinical ontologies and gene co-expression networks. Clinical phenotyping and exploration of cross-species similarities were further performed on a family-by-family basis. Statistical validation was performed on 248 ancestrally similar control trios provided by the Genome of the Netherlands project and on 574 ancestrally matched controls provided by the French Exome Project. Variants of clinical interest were identified in 180 genes significantly associated with key pathways of forebrain development including sonic hedgehog (SHH) and primary cilia. Oligogenic events were observed in 10 families and involved both known and novel holoprosencephaly genes including recurrently mutated FAT1, NDST1, COL2A1 and SCUBE2. The incidence of oligogenic combinations was significantly higher in holoprosencephaly patients compared to two control populations (P
Published: 2019
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134. A DNA virus-encoded immune antagonist fully masks the potent antiviral activity of RNAi in Drosophila

Author: Bas Pennings, Pascal Miesen, Gijs J. Overheul, Alfred W. Bronkhorst, Rob Vogels, Valérie Gausson-Dorey, Ronald P. van Rij, Radboud Institute for Molecular Life Sciences [Nijmegen, the Netherlands], Virus et Interférence ARN - Viruses and RNA Interference, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), This work was financially supported by a fellowship from the Radboud Institute for Molecular Life Sciences (Radboud University Medical Center) and by a Consolidator Grant from the European Research Council (ERC) under the European Union’s Seventh Framework Programme (ERC CoG 615680). Sequencing was performed by the GenomEast platform, a member of the 'France Génomique' consortium (ANR-10-INBS-0009)., We thank current and past members of the laboratory for fruitful discussions, especially Koen van Cleef for advice on gene deletion in DNA viruses. We thank Carla Saleh (Pasteur Institute) for hosting Drosophila injections in her laboratory, and Kathryn Rozen-Gagnon (Rockefeller University) for discussions., ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), European Project: 615680,EC:FP7:ERC,ERC-2013-CoG,VIVARNASILENCING(2014), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: Small interfering RNA, MESH: Drosophila, RNA Stability, [SDV]Life Sciences [q-bio], lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Virus Replication, RNA interference, MESH: Animals, insect immunity, viral suppressor of RNAi, 0303 health sciences, Multidisciplinary, MESH: Microorganisms, Genetically-Modified, 030302 biochemistry & molecular biology, MESH: RNA Stability, DNA virus, Biological Sciences, Argonaute, MESH: Gene Expression Regulation, MESH: Iridovirus, Cell biology, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Host-Pathogen Interactions, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Drosophila, RNA Interference, Microorganisms, Genetically-Modified, antiviral defense, MESH: Mutation, MESH: RNA Interference, Biology, Iridovirus, Viral Proteins, 03 medical and health sciences, All institutes and research themes of the Radboud University Medical Center, Animals, Gene silencing, Insect virus, 030304 developmental biology, MESH: Virus Replication, MESH: Host-Pathogen Interactions, fungi, RNA, insect virus, MESH: Viral Proteins, MicroRNAs, Gene Expression Regulation, Viral replication, RNAi, Mutation, MESH: MicroRNAs
Abstract: Coevolution of viruses and their hosts may lead to viral strategies to avoid, evade, or suppress antiviral immunity. An example is antiviral RNA interference (RNAi) in insects: the host RNAi machinery processes viral double-stranded RNA into small interfering RNAs (siRNAs) to suppress viral replication, whereas insect viruses encode suppressors of RNAi, many of which inhibit viral small interfering RNA (vsiRNA) production. Yet, many studies have analyzed viral RNAi suppressors in heterologous systems, due to the lack of experimental systems to manipulate the viral genome of interest, raising questions about in vivo functions of RNAi suppressors. To address this caveat, we generated an RNAi suppressor-defective mutant of invertebrate iridescent virus 6 (IIV6), a large DNA virus in which we previously identified the 340R protein as a suppressor of RNAi. Loss of 340R did not affect vsiRNA production, indicating that 340R binds siRNA duplexes to prevent RNA-induced silencing complex assembly. Indeed, vsiRNAs were not efficiently loaded into Argonaute 2 during wild-type IIV6 infection. Moreover, IIV6 induced a limited set of mature microRNAs in a 340R-dependent manner, most notably miR-305–3p, which we attribute to stabilization of the miR-305–5p:3p duplex by 340R. The IIV6 340R deletion mutant did not have a replication defect in cells, but was strongly attenuated in adult Drosophila . This in vivo replication defect was completely rescued in RNAi mutant flies, indicating that 340R is a bona fide RNAi suppressor, the absence of which uncovers a potent antiviral immune response that suppresses virus accumulation ∼100-fold. Together, our work indicates that viral RNAi suppressors may completely mask antiviral immunity.
Published: 2019
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135. Meta-omics reveals genetic flexibility of diatom nitrogen transporters in response to environmental changes

Author: Greta Busseni1, Fabio Rocha Jimenez Vieira2, Alberto Amato3, Eric Pelletier4, 5, Juan J. Pierella Karlusich2, Maria I. Ferrante1, Patrick Wincker4, Alessandra Rogato1, 6, Chris Bowler2, Remo Sanges1, 7, Luigi Maiorano1, 8, Maurizio Chiurazzi6, Maurizio Ribera d'Alcalà1, Luigi Caputi1, Daniele Iudicone1, Stazione Zoologica Anton Dohrn (SZN), Institut de biologie de l'ENS Paris (IBENS), Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), LIPID, Physiologie cellulaire et végétale (LPCV), Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Génomique métabolique (UMR 8030), Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Global Oceans Systems Ecology & Evolution - Tara Oceans (GOSEE), Université de Perpignan Via Domitia (UPVD)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Aix Marseille Université (AMU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université d'Évry-Val-d'Essonne (UEVE)-Université de Toulon (UTLN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche pour le Développement (IRD [France-Nord])-Ecole Normale Supérieure Paris-Saclay (ENS Paris Saclay)-European Molecular Biology Laboratory (EMBL)-École Centrale de Nantes (Nantes Univ - ECN), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Université australe du Chili, Institute of Biosciences and Bioresources, CNR, Scuola Internazionale Superiore di Studi Avanzati / International School for Advanced Studies (SISSA / ISAS), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Veolia Environment Foundation, Region Bretagne, World Courier, Illumina, Cap L'Orient, the EDF Foundation EDF Diversiterre, FRB, the Prince Albert II de Monaco Foundation, Etienne Bourgois, the Fonds Français pour l'Environnement Mondial, ANR-11-BTBR-0008,OCEANOMICS,Biotechnologies et bioressources pour la valorisation des écosystèmes marins planctoniques(2011), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), ANR-11-IDEX-0001,Amidex,INITIATIVE D'EXCELLENCE AIX MARSEILLE UNIVERSITE(2011), Stazione Zoologica Anton Dohrn, Institut de biologie de l'ENS Paris (UMR 8197/1024) (IBENS), École normale supérieure - Paris (ENS Paris)-École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Tara Oceans-GOSEE (FR2022), Università degli Studi di Roma 'La Sapienza' [Rome], ANR-11-BTBR-0008/11-BTBR-0008,OCEANOMICS,Biotechnologies et bioressources pour la valorisation des écosystèmes marins planctoniques(2011), ANR: ANR-10-INBS-09-08,The 'France Génomique' consortium, ANR-11-IDEX-0001-02,PSL Research University, Martin-Laffon, Jacqueline, Biotech - Bioressources - Biotechnologies et bioressources pour la valorisation des écosystèmes marins planctoniques - - OCEANOMICS2011 - ANR-11-BTBR-0008 - BTBR - VALID, Organisation et montée en puissance d'une Infrastructure Nationale de Génomique - - France-Génomique2010 - ANR-10-INBS-0009 - INBS - VALID, INITIATIVE D'EXCELLENCE AIX MARSEILLE UNIVERSITE - - Amidex2011 - ANR-11-IDEX-0001 - IDEX - VALID, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Département de Biologie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université d'Évry-Val-d'Essonne (UEVE), and Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome]
Subjects: 0106 biological sciences, Ocean, nitrogen transporters, Metatranscriptome, Tara Oceans, Biology, 010603 evolutionary biology, 01 natural sciences, diatoms, 03 medical and health sciences, chemistry.chemical_compound, Nutrient, Water column, [SDV.EE.ECO]Life Sciences [q-bio]/Ecology, environment/Ecosystems, Nitrate, Phylogenetics, meta-omics, machine learning, Phytoplankton, Genetics, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.EE.ECO] Life Sciences [q-bio]/Ecology, environment/Ecosystems, Gene family, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, 14. Life underwater, Di NRT2, TARA, Molecular Biology, Ecology, Evolution, Behavior and Systematics, Discoveries, Phylogeny, 030304 developmental biology, 0303 health sciences, Ecology, fungi, biology.organism_classification, Diatom, chemistry, Di AMT1, Metagenomics, Nutrient transport, Metagenome, Gene expression, Nitrogen uptake, Settore BIO/03 - Botanica Ambientale e Applicata
Abstract: Diatoms (Bacillariophyta), one of the most abundant and diverse groups of marine phytoplankton, respond rapidly to the supply of new nutrients, often out-competing other phytoplankton. Herein, we integrated analyses of the evolution, distribution, and expression modulation of two gene families involved in diatom nitrogen uptake (DiAMT1 and DiNRT2), in order to infer the main drivers of divergence in a key functional trait of phytoplankton. Our results suggest that major steps in the evolution of the two gene families reflected key events triggering diatom radiation and diversification. Their expression is modulated in the contemporary ocean by seawater temperature, nitrate, and iron concentrations. Moreover, the differences in diversity and expression of these gene families throughout the water column hint at a possible link with bacterial activity. This study represents a proof-of-concept of how a holistic approach may shed light on the functional biology of organisms in their natural environment.
Published: 2019
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136. Draft genome assembly and annotation of the gila topminnow Poeciliopsis occidentalis

Author: Mateos, Mariana, Kang, Du, Klopp, Christophe, Parrinello, Hugues, Garcia-Olazabal, Mateo, Schumer, Molly, Jue, Nathaniel K., Guiguen, Yann, Schartl, Manfred, Texas A&M University [College Station], University of Würzburg = Universität Würzburg, Unité de Mathématiques et Informatique Appliquées de Toulouse (MIAT INRA), Institut National de la Recherche Agronomique (INRA), Institut de Génomique Fonctionnelle - Montpellier GenomiX (IGF MGX), Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Department of Biology, Texas A&M University, Partenaires INRAE, Howard Hughes Medical Institute (HHMI) and Department of Biology, Stanford University, Department of Biology and Chemistry, California State University Monterey Bay, Laboratoire de Physiologie et Génomique des Poissons (LPGP), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Recherche Agronomique (INRA), This work was supported by NSF DEB 9902224 to R. C. Vrijenhoek and MM. MScha was supported by the Hagler Institute of Advanced Study of Texas A&M University and funds provided by the Department of Biology of Texas A&M University and the Biocenter, Chair Physiologische Chemie, University of Würzburg. MG-O was supported by a Heep fellowship. HP acknowledges financial support from the France Génomique National infrastructure, funded as part of Investissement d’Avenir program managed by Agence Nationale de la Recherche (contract ANR-10-INBS-09). NSF Project Grant IOS-0920088 to M.J. O’Neill and R.J. O’Neill, NSF-MRI 0821466 to Linda Strausbaugh and R.J. O’Neill, and NSF-MRI-R2 0959365 to M.J. O’Neill and R.J. O’Neill. T., and ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010)
Subjects: fish, genome annotation, [SDV]Life Sciences [q-bio], tool, prediction, conservation genetics, mitochondrial genome, evolution, genome assembly, transposable elements, topminnow, [INFO]Computer Science [cs], ddc:610, [MATH]Mathematics [math], ComputingMilieux_MISCELLANEOUS
Abstract: No abstract available.
Published: 2019
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137. Gene flow contributes to diversification of the major fungal pathogen $Candida\ albicans$

Author: Marie-Elisabeth Bougnoux, Gavin Sherlock, Patrick Wincker, Marina Marcet-Houben, Emmanuelle Permal, Toni Gabaldón, Dorothée Diogo, Christophe Battail, Natacha Sertour, Patrice Le Pape, Laurence Ma, Jong Hee Shin, Andrew M. Borman, Julie Poulain, Robin C. May, Jeanne Ropars, Soo Hyun Kim, Christiane Bouchier, Kevin Mosca, Shangrong Fan, Christophe d'Enfert, Corinne Maufrais, Kerstin Voelz, Orazio Romeo, Guillaume Laval, Anuradha Chowdhary, Aurélie Perin, Katja Schwartz, Ecologie Systématique et Evolution (ESE), Université Paris-Sud - Paris 11 (UP11)-AgroParisTech-Centre National de la Recherche Scientifique (CNRS), Biologie et Pathogénicité fongiques, Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris], Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Center for Genomic Regulation (CRG-UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), Universitat Pompeu Fabra [Barcelona], Unité de Recherche Génomique Info (URGI), Institut National de la Recherche Agronomique (INRA), Génétique Evolutive Humaine - Human Evolutionary Genetics, Génomique (Plate-Forme), Institut Pasteur [Paris], Centre de Recherche et Innovation Technologique (CITECH), Stanford University [Stanford], University of Birmingham [Birmingham], Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Génomique métabolique (UMR 8030), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université d'Évry-Val-d'Essonne (UEVE), Public Health England [London], University of Delhi, Peking University [Beijing], Chonnam National University [Gwangju], Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), University of Messina, Centro Neurolesi Bonino Pulejo Messina (IRCCS Messina), Centro de Regulación Genómica (CRG), ICREA Infection Biology Laboratory (Department of Experimental and Health Sciences), Université Paris Descartes - Paris 5 (UPD5), CHU Necker - Enfants Malades [AP-HP], the Genoscope (projet #15 AP2008/2009 SNP C. albicans) and the Swiss National Science Foundation (Sinergia CRSII5_173863/1) to C.E., J.R. was supported by a Pasteur-Roux fellowship from Institut Pasteur. D.D. was the recipient of a PhD fellowship from Institut National de la Recherche Agronomique. E.P. was the recipient of a post-doctoral fellowship from the Wellcome Trust (WT088858MA). M.M.-H. and T.G. were supported by a grant from the Spanish Ministry of Economy and Competitiveness, BFU2015–67107 cofunded by the European Regional Development Fund (ERDF). C.E., M.-E.B., S.H.K., and J.H.S. were supported by a grant from the French and Korean Ministries for Foreign Affairs (PHC STAR 2011 25841YA). R.C.M. was supported by project MitoFun, funded by the European Research Council under the European Union’s Seventh Framework Programme (FP/2007–2013)/ERC Grant Agreement No. 614562 and by a Wolfson Research Merit Award from the Royal Society. R.C.M. and K.V. were funded by the Surgical Reconstruction and Microbiology Research Centre, which is supported by the National Institute of Health Research, UK. G.S. was supported by the NIH grants R01-HG003468 and RO1-DE015873. C.E. and T.G. are members of the CNRS GDRI 0814 iGenolevures consortium. High-throughput sequencing has been performed on the Genomics Platform, member of France Génomique consortium (ANR10-INBS-09-08)., We thank Bernard Dujon and Tatiana Giraud for providing insights on an earlier version of this manuscript., ANR-10-LABX-62-IBEID,IBEID,Laboratoire d'Excellence 'Integrative Biology of Emerging Infectious Diseases'(2010), ANR-10-INBS-09-01/10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), European Project: 614562,EC:FP7:ERC,ERC-2013-CoG,MITOFUN(2014), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Biologie et Pathogénicité fongiques (BPF), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Universitat Pompeu Fabra [Barcelona] (UPF), Génomique (Plate-Forme) - Genomics Platform, Institut Pasteur [Paris] (IP), Stanford University, Cibles et Médicaments des Infections et de l'Immunité (IICiMed), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), and Institut Pasteur [Paris]-Institut National de la Recherche Agronomique (INRA)
Subjects: 0301 basic medicine, Gene Flow, Lineage (genetic), Population genetics, Science, [SDV]Life Sciences [q-bio], Genes, Fungal, education, General Physics and Astronomy, Virulence, Loss of Heterozygosity, Polymorphism, Single Nucleotide, General Biochemistry, Genetics and Molecular Biology, Article, Linkage Disequilibrium, Gene flow, 03 medical and health sciences, Gene Frequency, Species Specificity, Candida albicans, Humans, lcsh:Science, Phylogeny, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Genetics, Genetic diversity, Multidisciplinary, biology, Whole Genome Sequencing, Candidiasis, Genetic Variation, General Chemistry, biology.organism_classification, Corpus albicans, 3. Good health, 030104 developmental biology, GENERATION SEQUENCING DATA, VULVO-VAGINAL CANDIDIASIS, PARASEXUAL CYCLE, MOLECULAR PHYLOGENETICS, CLINICAL STRAINS, DUBLINIENSIS, AFRICANA, REVEALS, YEAST, DNA, Microbial genetics, lcsh:Q, Pathogens
Abstract: Elucidating population structure and levels of genetic diversity and recombination is necessary to understand the evolution and adaptation of species. Candida albicans is the second most frequent agent of human fungal infections worldwide, causing high-mortality rates. Here we present the genomic sequences of 182 C. albicans isolates collected worldwide, including commensal isolates, as well as ones responsible for superficial and invasive infections, constituting the largest dataset to date for this major fungal pathogen. Although, C. albicans shows a predominantly clonal population structure, we find evidence of gene flow between previously known and newly identified genetic clusters, supporting the occurrence of (para)sexuality in nature. A highly clonal lineage, which experimentally shows reduced fitness, has undergone pseudogenization in genes required for virulence and morphogenesis, which may explain its niche restriction. Candida albicans thus takes advantage of both clonality and gene flow to diversify., The fungal pathogen Candida albicans can undergo a parasexual process that may contribute to genetic diversity, but its actual relevance is unclear. Here, Ropars et al. analyse the genomic sequences of 182 C. albicans isolates collected worldwide and find evidence of gene flow and thus parasexuality in nature.
Published: 2018
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138. Cracking the wheat code – one giant leap for science, one small step for agriculture

Author: Paux, Etienne, Génétique Diversité et Ecophysiologie des Céréales (GDEC), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Institut National de la Recherche Agronomique (INRA), ProdInra, Archive Ouverte, Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Recherche Agronomique (INRA), France Génomique., Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), ProdInra, Migration, and Institut National de la Recherche Agronomique (INRA)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)
Subjects: [SDE] Environmental Sciences, [SDV] Life Sciences [q-bio], blé, wheat, [SDV]Life Sciences [q-bio], [SDE]Environmental Sciences, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, [SDV.BV] Life Sciences [q-bio]/Vegetal Biology, génomique végétale, ComputingMilieux_MISCELLANEOUS, agriculture
Abstract: Cracking the wheat code – one giant leap for science, one small step for agriculture. International Symposium on Environmental and Agronomical Genomics
Published: 2018

139. Sequana Coverage: Detection and Characterization of Genomic Variations using Running Median and Mixture Models

Author: Christiane Bouchier, Sean Kennedy, Dimitri Desvillechabrol, Thomas Cokelaer, Pôle Biomics (C2RT), Centre de Ressources et de Recherche Technologique - Center for Technological Resources and Research (C2RT), Institut Pasteur [Paris]-Institut Pasteur [Paris], Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), This work has been supported by the France Génomique Consortium (ANR 10-INBS-09-08)., We are grateful to Nicolas Escriou (Institut Pasteur) for providing the FastQ and reference of the virus test case. We are also grateful to Benoit Arcangioli (Institut Pasteur) and Serge Gangloff (Institut Pasteur) for providing the FastQ files and reference of the S. pombe test case. We thank Juliana Pipoli da Fonseca for her various comments on the manuscript. We are also grateful to the reviewers who suggested the CNV studies, ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), Institut Pasteur [Paris] (IP)-Institut Pasteur [Paris] (IP), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, DNA Copy Number Variations, Computer science, CNV, Sequencing data, Robust statistics, Health Informatics, Computational biology, Disease cluster, Genome, 03 medical and health sciences, sequencing depth, mental disorders, Technical Note, Copy-number variation, Statistic, Snakemake, running median, Bacteria, Fungi, Genetic Variation, High-Throughput Nucleotide Sequencing, Sequana, Repetitive Regions, Mixture model, Computer Science Applications, 030104 developmental biology, genome coverage, NGS, Viruses, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Algorithms, Python
Abstract: International audience; Background:In addition to mapping quality information, the Genome coverage contains valuable biological information such as the presence of repetitive regions, deleted genes, or copy number variations (CNVs). It is essential to take into consideration atypical regions, trends (e.g., origin of replication), or known and unknown biases that influence coverage. It is also important that reported events have robust statistics (e.g. z-score) associated with their detections as well as precise location.Results:We provide a stand-alone application, sequana_coverage, that reports genomic regions of interest (ROIs) that are significantly over- or underrepresented in high-throughput sequencing data. Significance is associated with the events as well as characteristics such as length of the regions. The algorithm first detrends the data using an efficient running median algorithm. It then estimates the distribution of the normalized genome coverage with a Gaussian mixture model. Finally, a z-score statistic is assigned to each base position and used to separate the central distribution from the ROIs (i.e., under- and overcovered regions). A double thresholds mechanism is used to cluster the genomic ROIs. HTML reports provide a summary with interactive visual representations of the genomic ROIs with standard plots and metrics. Genomic variations such as single-nucleotide variants or CNVs can be effectively identified at the same time.
Published: 2018
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140. Unexpected Genomic and Phenotypic Diversity of Mycobacterium africanum Lineage 5 Affects Drug Resistance, Protein Secretion, and Immunogenicity

Author: Wladimir Sougakoff, Roland Brosch, Florence Brossier, Anzaan Dippenaar, Alexandre Pawlik, Fadel Sayes, Laleh Majlessi, Jeroen W. J. van Heijst, Robin M. Warren, Laurence Ma, Christiane Bouchier, Louis S. Ates, Pathogénomique mycobactérienne intégrée - Integrated Mycobacterial Pathogenomics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Stellenbosch University, Génomique (Plate-Forme) - Genomics Platform, Institut Pasteur [Paris] (IP), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), This work was supported in part by the French National Research Council ANR (ANR-14-JAMR-001-02, ANR-10-LABX-62-IBEID, ANR-16-CE35-0009, ANR-16-CE15-0003), the Fondation pour la Recherche Médicale (DEQ20130326471) and the European Union’s Horizon 2020 Research and Innovation Program (643381). LSA and JWJvH are supported by the Netherlands Organisation for Scientific Research (Vidi grant 91717305 to JWJvH). The Genomics Platform of the Institut Pasteur is a member of 'France Génomique' consortium (ANR10-INBS-09-08). This study was supported in part by the South African Medical Research Council., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-14-JAMR-0001,noTBsec,New intervention strategy for tuberculosis: blocking multiple essential targets(2014), ANR-16-CE35-0009,TBemerg,Naissance d'un tueur: facteurs génétiques et adaptations métaboliques impliquées dans l'émergence des bacilles tuberculeux épidémiques(2016), ANR-16-CE15-0003,MTBLipVir,Analyse multi-échelle et multidisciplinaire des mécanismes intimes d'action des lipides de virulence de l'enveloppe de Mycobacterium tuberculosis(2016), European Project: 643381,H2020,H2020-PHC-2014-single-stage,TBVAC2020(2015), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris], Centre d'Immunologie et de Maladies Infectieuses (CIMI), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), HAL UPMC, Gestionnaire, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, programmation conjointe européenne sur la résistance antimicrobienne - New intervention strategy for tuberculosis: blocking multiple essential targets - - noTBsec2014 - ANR-14-JAMR-0001 - JPI AMR - VALID, Naissance d'un tueur: facteurs génétiques et adaptations métaboliques impliquées dans l'émergence des bacilles tuberculeux épidémiques - - TBemerg2016 - ANR-16-CE35-0009 - AAPG2016 - VALID, Analyse multi-échelle et multidisciplinaire des mécanismes intimes d'action des lipides de virulence de l'enveloppe de Mycobacterium tuberculosis - - MTBLipVir2016 - ANR-16-CE15-0003 - AAPG2016 - VALID, TBVAC2020, Advancing novel and promising TB vaccine candidates from discovery to preclinical and early clinical development - TBVAC2020 - - H20202015-01-01 - 2018-12-31 - 643381 - VALID, Experimental Immunology, and AII - Infectious diseases
Subjects: Adult, Genetic Markers, Male, 0301 basic medicine, Genotype, Antibiotic resistance, T-Lymphocytes, [SDV]Life Sciences [q-bio], 030106 microbiology, Genomics, Genome, Mycobacterium, Mycobacterium tuberculosis, 03 medical and health sciences, Bacterial Proteins, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Drug Resistance, Bacterial, Isoniazid, Genetics, Tuberculosis, Animals, Humans, Base Pairing, Phylogeny, Ecology, Evolution, Behavior and Systematics, Sequence Deletion, Mycobacterium africanum, biology, Immunogenicity, Computational Biology, Phenotypic trait, Middle Aged, biology.organism_classification, 3. Good health, Mice, Inbred C57BL, [SDV] Life Sciences [q-bio], Phenotype, Mycobacterium tuberculosis complex, PhoPR, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, Lineage 5, PPE38, Research Article
Abstract: International audience; Mycobacterium africanum consists of Lineages L5 and L6 of the Mycobacterium tuberculosis complex (MTBC) and causes human tuberculosis in specific regions of Western Africa, but is generally not transmitted in other parts of the world. Since M. africanum is evolutionarily closely placed between the globally dispersed Mycobacterium tuberculosis and animal-adapted MTBC-members, these lineages provide valuable insight into M. tuberculosis evolution. Here, we have collected 15 M. africanum L5 strains isolated in France over 4 decades. Illumina sequencing and phylogenomic analysis revealed a previously underappreciated diversity within L5, which consists of distinct sublineages. L5 strains caused relatively high levels of extrapulmonary tuberculosis and included multi- and extensively drug-resistant isolates, especially in the newly defined sublineage L5.2. The specific L5 sublineages also exhibit distinct phenotypic characteristics related to in vitro growth, protein secretion and in vivo immunogenicity. In particular, we identified a PE_PGRS and PPE-MPTR secretion defect specific for sublineage L5.2, which was independent of PPE38. Furthermore, L5 isolates were able to efficiently secrete and induce immune responses against ESX-1 substrates contrary to previous predictions. These phenotypes of Type VII protein secretion and immunogenicity provide valuable information to better link genome sequences to phenotypic traits and thereby understand the evolution of the MTBC.
Published: 2018
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141. Enteric bacteria boost defences against oxidative stress in Entamoeba histolytica

Author: Hugo Varet, Yana Shaulov, Odile Sismeiro, Meirav Trebicz-Geffen, Rachel Legendre, Jean-Yves Coppée, Serge Ankri, Nancy Guillen, Transcriptome et Epigénome (PF2), Institut Pasteur [Paris], Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Technion - Israel Institute of Technology [Haifa], Centre National de la Recherche Scientifique (CNRS), The project has received funding from the European ERA-NET Infect-ERA program AMOEBAC (Israel Ministry of Health Grant 031L000 and the French National Agency for Research (ANR) grants ANR-14-IFEC-0001-01 and ANR-14-IFEC-0001-02) and the French Parasitology consortium Labex ParaFrap (through the grant ANR-11-LABX0024). The Transcriptome and Epigenome Platform is a member of the France Génomique consortium (ANR10‐NBS‐09‐08)., ANR-14-IFEC-0001,AMOEBAC,Entamoeba histolytica-bacterium interaction and the role of this interaction in intestinal pathogenesis.(2014), ANR-11-LABX-0024,ParaFrap,Alliance française contre les maladies parasitaires(2011), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), Institut Pasteur [Paris] (IP), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
Subjects: lcsh:R, Entamoeba histolytica, Protozoan Proteins, lcsh:Medicine, Immunity, Innate, Article, Gastrointestinal Microbiome, Intestines, Oxidative Stress, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Enterobacteriaceae, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], parasitic diseases, Escherichia coli, Homeostasis, Humans, lcsh:Q, lcsh:Science, Transcriptome
Abstract: International audience; Oxidative stress is one of the strongest toxic factors in nature: it can harm or even kill cells. Cellular means of subverting the toxicity of oxidative stress are important for the success of infectious diseases. Many types of bacterium inhabit the intestine, where they can encounter pathogens. During oxidative stress, we analyzed the interplay between an intestinal parasite (the pathogenic amoeba Entamoeba histolytica - the agent of amoebiasis) and enteric bacteria (microbiome residents, pathogens and probiotics). We found that live enteric bacteria protected E. histolytica against oxidative stress. By high-throughput RNA sequencing, two amoebic regulatory modes were observed with enteric bacteria but not with probiotics. The first controls essential elements of homeostasis, and the second the levels of factors required for amoeba survival. Characteristic genes of both modes have been acquired by the amoebic genome through lateral transfer from the bacterial kingdom (e.g. glycolytic enzymes and leucine-rich proteins). Members of the leucine-rich are homologous to proteins from anti-bacterial innate immune such as Toll-like receptors. The factors identified here suggest that despite its old age in evolutionary terms, the protozoan E. histolytica displays key characteristics of higher eukaryotes' innate immune systems indicating that components of innate immunity existed in the common ancestor of plants and animals.
Published: 2018
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142. Expansion of the SOS regulon of Vibrio cholerae through extensive transcriptome analysis and experimental validation

Author: Jean-Yves Coppée, Bernd Jagla, Zoé Rouy, Hugo Varet, Didier Mazel, Claudine Médigue, Oihane Irazoki, Evelyne Krin, Stéphane Cruveiller, Sebastian Aguilar Pierlé, Odile Sismeiro, Susana Campoy, Marie-Agnès Dillies, Plasticité du Génome Bactérien - Bacterial Genome Plasticity (PGB), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Transcriptome et Epigénome (PF2), Institut Pasteur [Paris] (IP), Universitat Autònoma de Barcelona (UAB), Génomique métabolique (UMR 8030), Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), This study was funded by the Institut Pasteur, the Centre National de la Recherche Scientifique (CNRS-UMR3525), the French National Research Agency (ANR-2012-Blanc SVSE3-DynamINT), the French Government’s Investissement d’Avenir program, Laboratoire d’Excellence 'Integrative Biology of Emerging Infectious Diseases' (grant n°ANR-10-LABX-62-IBEID), the Spanish the Ministerio de Economía y Competitividad (BIO2016–77011-R), Generalitat de Catalunya (2014SGR 572), and the European Union Seventh Framework Programme (FP7-HEALTH-2011-single-stage) 'Evolution and Transfer of Antibiotic Resistance' (EvoTAR). The Transcriptome and EpiGenome Platform is a member of the France Génomique consortium (ANR10-NBS-09-08)., ANR-12-BSV3-0015,DynamINT,Recombination des cassettes d'intégron: dynamique in vivo et in vitro(2012), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), European Project: 282004,EC:FP7:HEALTH,FP7-HEALTH-2011-single-stage,EVOTAR(2011), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris], and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université d'Évry-Val-d'Essonne (UEVE)
Subjects: NcRNA, 0301 basic medicine, SOS response, lcsh:QH426-470, lcsh:Biotechnology, [SDV]Life Sciences [q-bio], Mitomycin, genetic processes, 030106 microbiology, DNA repair, Biology, medicine.disease_cause, Regulon, Transcriptome, 03 medical and health sciences, SOS Response (Genetics), lcsh:TP248.13-248.65, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Genetics, medicine, SOS Response, Genetics, Vibrio cholerae, Gene, Gene Expression Profiling, Promoter, biochemical phenomena, metabolism, and nutrition, ncRNA, nrdB, nrdA, lcsh:Genetics, enzymes and coenzymes (carbohydrates), Phenotype, bacteria, Repressor lexA, Transcription Initiation Site, NrdB, 5' Untranslated Regions, NrdA, Research Article, Biotechnology
Abstract: Background The SOS response is an almost ubiquitous response of cells to genotoxic stresses. The full complement of genes in the SOS regulon for Vibrio species has only been addressed through bioinformatic analyses predicting LexA binding box consensus and in vitro validation. Here, we perform whole transcriptome sequencing from Vibrio cholerae treated with mitomycin C as an SOS inducer to characterize the SOS regulon and other pathways affected by this treatment. Results Comprehensive transcriptional profiling allowed us to define the full landscape of promoters and transcripts active in V. cholerae. We performed extensive transcription start site (TSS) mapping as well as detection/quantification of the coding and non-coding RNA (ncRNA) repertoire in strain N16961. To improve TSS detection, we developed a new technique to treat RNA extracted from cells grown in various conditions. This allowed for identification of 3078 TSSs with an average 5’UTR of 116 nucleotides, and peak distribution between 16 and 64 nucleotides; as well as 629 ncRNAs. Mitomycin C treatment induced transcription of 737 genes and 28 ncRNAs at least 2 fold, while it repressed 231 genes and 17 ncRNAs. Data analysis revealed that in addition to the core genes known to integrate the SOS regulon, several metabolic pathways were induced. This study allowed for expansion of the Vibrio SOS regulon, as twelve genes (ubiEJB, tatABC, smpA, cep, VC0091, VC1190, VC1369–1370) were found to be co-induced with their adjacent canonical SOS regulon gene(s), through transcriptional read-through. Characterization of UV and mitomycin C susceptibility for mutants of these newly identified SOS regulon genes and other highly induced genes and ncRNAs confirmed their role in DNA damage rescue and protection. Conclusions We show that genotoxic stress induces a pervasive transcriptional response, affecting almost 20% of the V. cholerae genes. We also demonstrate that the SOS regulon is larger than previously known, and its syntenic organization is conserved among Vibrio species. Furthermore, this specific co-localization is found in other γ-proteobacteria for genes recN-smpA and rmuC-tatABC, suggesting SOS regulon conservation in this phylum. Finally, we comment on the limitations of widespread NGS approaches for identification of all RNA species in bacteria. Electronic supplementary material The online version of this article (10.1186/s12864-018-4716-8) contains supplementary material, which is available to authorized users.
Published: 2018
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143. In cell mutational interference mapping experiment (in cell MIME) identifies the 5′ polyadenylation signal as a dual regulator of HIV-1 genomic RNA production and packaging

Author: Redmond P. Smyth, Maureen R. Smith, Laurence Despons, Anne-Caroline Jousset, Pierre B. Cattenoz, Roland Marquet, Thomas Decoville, Marylène Mougel, Fabrice Jossinet, Jean-Christophe Paillart, Géraldine Laumond, Christiane Moog, Max von Kleist, Architecture et Réactivité de l'ARN (ARN), Institut de biologie moléculaire et cellulaire (IBMC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Department of Mathematics and Computer Science (Freie Universität Berlin), Freie Universität Berlin, Immuno-Rhumatologie Moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Institut de Recherche en Infectiologie de Montpellier (IRIM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Sidaction and ANRS (Agence Nationale de Recherches sur le SIDA et les Hépatites Virales) to R.M., ANRS [ECTZ35556 to R.P.S.] and IDEX: Par delà les frontières, l’Université de Strasbourg to R.P.S., German Ministry for Education & Science (BMBF) [031A307 to M.S. and M.v.K.], Partenariat Hubert Curien (PHC) programme franco-allemand PROCOPE [37709NJ to R.P.S. and M.v.K.], IGBMC Microarray and Sequencing platform, a member of the ‘France Génomique’ consortium [ANR-10-INBS-0009]. Funding for open access charge: CNRS., ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), Mougel, Marylene, Organisation et montée en puissance d'une Infrastructure Nationale de Génomique - - France-Génomique2010 - ANR-10-INBS-0009 - INBS - VALID, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), and ANR-10-INBS-09-01/10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010)
Subjects: 0301 basic medicine, Polyadenylation, [SDV]Life Sciences [q-bio], Regulator, Aucun, Genome, Viral, Computational biology, Regulatory Sequences, Ribonucleic Acid, Biology, Virus Replication, Genome, 03 medical and health sciences, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Genetics, Humans, Nucleotide, Guide RNA, Nucleotide Motifs, chemistry.chemical_classification, Virus Assembly, RNA, HEK293 Cells, 030104 developmental biology, chemistry, Viral replication, Mutation, HIV-1, Methods Online, RNA, Viral, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], RNA characterisation and manipulation, 5' Untranslated Regions, Poly A, Intracellular
Abstract: International audience; Non-coding RNA regulatory elements are important for viral replication, making them promising targets for therapeutic intervention. However, regulatory RNA is challenging to detect and characterise using classical structure-function assays. Here, we present in cell Mutational Interference Mapping Experiment (in cell MIME) as a way to define RNA regulatory landscapes at single nucleotide resolution under native conditions. In cell MIME is based on (i) random mutation of an RNA target, (ii) expression of mutated RNA in cells, (iii) physical separation of RNA into functional and non-functional populations, and (iv) high-throughput sequencing to identify mutations affecting function. We used in cell MIME to define RNA elements within the 5' region of the HIV-1 genomic RNA (gRNA) that are important for viral replication in cells. We identified three distinct RNA motifs controlling intracellular gRNA production, and two distinct motifs required for gRNA packaging into virions. Our analysis reveals the 73AAUAAA78 polyadenylation motif within the 5' PolyA domain as a dual regulator of gRNA production and gRNA packaging, and demonstrates that a functional polyadenylation signal is required for viral packaging even though it negatively affects gRNA production.
Published: 2018
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144. Cell-Cycle-Dependent Reconfiguration of the DNA Methylome during Terminal Differentiation of Human B Cells into Plasma Cells

Author: Mourad Hussein, Céline Delaloy, Ana C. Queirós, Elise A. Mahé, Fabrice Chatonnet, José I. Martín-Subero, Maud Lemarié, Gilles Salbert, Marta Kulis, Thierry Fest, Stéphane Avner, Amandine Pignarre, Núria Verdaguer-Dot, Karin Tarte, Gersende Caron, Universitat de Barcelona, Pôle biologie, Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Etablissement français du sang [Rennes] (EFS Bretagne), Microenvironnement et cancer (MiCa), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Universitat de Barcelona (UB), Etablissement Français du Sang Bretagne, EFS, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), This work was supported by an internal grant from the Hematology laboratory, Pôle de biologie, CHU de Rennes, France, the Ligue Nationale contre le Cancer (Equipe labellisée), and the European Union’s Seventh Framework Program through the Blueprint Consortium. M.H. was supported by a research grant from La Ligue contre le Cancer/Région Bretagne. G.S. was supported by the CNRS and the University of Rennes 1 and by grants from La Ligue contre le Cancer and Cancéropole Grand Ouest. E.A.M. was supported by a Ph.D. fellowship from the Ministère de l’enseignement supérieur et de la recherche. Sequencing was performed by the IGBMC Microarray and Sequencing platform, a member of the France Génomique consortium (ANR-10-INBS-0009), and the Biogenouest Genomics/Human & Environmental Genomics core facility of Rennes (Biosit/OSUR). Cell sorting was performed at the Biosit Flow Cytometry and CellSorting Facility (University of Rennes 1, France)., ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), Jonchère, Laurent, Organisation et montée en puissance d'une Infrastructure Nationale de Génomique - - France-Génomique2010 - ANR-10-INBS-0009 - INBS - VALID, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: Cèl·lules B, Cellular differentiation, Plasma Cells, ADN, Naive B cell, [SDV.CAN]Life Sciences [q-bio]/Cancer, plasma cell differentiation, Plasma cell, Cell fate determination, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Transforming Growth Factor beta, Plasma cell differentiation, medicine, Humans, Smad3 Protein, B cell differentiation, lcsh:QH301-705.5, Cells, Cultured, 030304 developmental biology, B cells, 0303 health sciences, DNA methylation, CD40, biology, Receptors, IgE, Lymphopoiesis, Cell Cycle, DNA, Cell cycle, Molecular biology, Repressor Proteins, medicine.anatomical_structure, lcsh:Biology (General), 030220 oncology & carcinogenesis, plasmablast, biology.protein, 5hmC, Positive Regulatory Domain I-Binding Factor 1, Tumor Suppressor Protein p53
Abstract: International audience; Molecular mechanisms underlying terminal differentiation of B cells into plasma cells are major determinants of adaptive immunity but remain only partially understood. Here we present the transcriptional and epigenomic landscapes of cell subsets arising from activation of human naive B cells and differentiation into plasmablasts. Cell proliferation of activated B cells was linked to a slight decrease in DNA methylation levels, but followed by a committal step in which an S phase-synchronized differentiation switch was associated with an extensive DNA demethylation and local acquisition of 5-hydroxymethylcytosine at enhancers and genes related to plasma cell identity. Downregulation of both TGFβ1/SMAD3 signaling and p53 pathway supported this final step, allowing the emergence of a CD23-negative subpopulation in transition from B cells to plasma cells. Remarkably, hydroxymethylation of PRDM1, a gene essential for plasma cell fate, was coupled to progression in S phase, revealing an intricate connection among cell cycle, DNA (hydroxy) methylation, and cell fate determination.
Published: 2015
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145. A novel species of the marine cyanobacterium Acaryochloris with a unique pigment content and lifestyle

Author: Morgane Ratin, Christiane Bouchier, Laurence Garczarek, Dominique Marie, Francisco Rodríguez, José L. Garrido, Christophe Six, Alexandra Calteau, Ian Probert, Sophie Le Panse, Frédéric Partensky, Martin Gachenot, Daniel Vaulot, Priscillia Gourvil, Théophile Grébert, Station biologique de Roscoff (SBR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Fédération de recherche de Roscoff (FR2424), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Procaryotes Phototrophes Marins = MArine Phototrophic Prokaryotes (MAPP), Adaptation et diversité en milieu marin (ADMM), Institut national des sciences de l'Univers (INSU - CNRS)-Station biologique de Roscoff (SBR), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Station biologique de Roscoff (SBR), Génomique (Plate-Forme) - Genomics Platform, Institut Pasteur [Paris] (IP), Instituto Espanol de Oceanografia, Instituto Español de Oceanografía, Instituto de Investigaciones Marinas de Vigo, Instituto de Investigaciones Marinas, This work is a contribution of Microalgas Nocivas, IEO, Unidad Asociada al IIM (CSIC). We thank Pascal Morin for providing in situ temperature and salinity data for the RCC1774 isolation site, Laurence Ma (Genomics Platform) for technical help and Gregory K. Farrant for assistance with phylogenetic analyses. The Genomics Platform of the Pasteur Institute is a member of the 'France Génomique' consortium (ANR10-INBS-09-08)., ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), Station biologique de Roscoff [Roscoff] ( SBR ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ), Genoscope - Centre national de séquençage [Evry] ( GENOSCOPE ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), MArine Phototrophic Prokaryotes ( MAPP ), Adaptation et diversité en milieu marin ( ADMM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ), Génomique (Plate-Forme), Institut Pasteur [Paris], Universidad de Alicante, MArine Phototrophic Prokaryotes (MAPP), Adaptation et diversité en milieu marin (AD2M), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Station biologique de Roscoff (SBR), and Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Cyanobacteria, Chlorophyll, Medio Marino y Protección Ambiental, Prochloron, lcsh:Medicine, macromolecular substances, Article, [ SDE ] Environmental Sciences, 03 medical and health sciences, Centro Oceanográfico de Vigo, Phycocyanin, polycyclic compounds, Prochlorothrix, 14. Life underwater, lcsh:Science, ComputingMilieux_MISCELLANEOUS, [ SDE.BE ] Environmental Sciences/Biodiversity and Ecology, Multidisciplinary, Allophycocyanin, biology, Chemistry, Phycobiliprotein, Chlorophyll A, lcsh:R, food and beverages, biology.organism_classification, 030104 developmental biology, Biochemistry, Phytoplankton, [SDE]Environmental Sciences, Phycobilisome, lcsh:Q, Prochlorococcus, [SDE.BE]Environmental Sciences/Biodiversity and Ecology
Abstract: 13 pages, 7 figures.-- Frédéric Partensky ... et al.-- This article is licensed under a Creative Commons Attribution 4.0 International License, All characterized members of the ubiquitous genus Acaryochloris share the unique property of containing large amounts of chlorophyll (Chl) d, a pigment exhibiting a red absorption maximum strongly shifted towards infrared compared to Chl a. Chl d is the major pigment in these organisms and is notably bound to antenna proteins structurally similar to those of Prochloron, Prochlorothrix and Prochlorococcus, the only three cyanobacteria known so far to contain mono- or divinyl-Chl a and b as major pigments and to lack phycobilisomes. Here, we describe RCC1774, a strain isolated from the foreshore near Roscoff (France). It is phylogenetically related to members of the Acaryochloris genus but completely lacks Chl d. Instead, it possesses monovinyl-Chl a and b at a b/a molar ratio of 0.16, similar to that in Prochloron and Prochlorothrix. It differs from the latter by the presence of phycocyanin and a vestigial allophycocyanin energetically coupled to photosystems. Genome sequencing confirmed the presence of phycobiliprotein and Chl b synthesis genes. Based on its phylogeny, ultrastructural characteristics and unique pigment suite, we describe RCC1774 as a novel species that we name Acaryochloris thomasi. Its very unusual pigment content compared to other Acaryochloris spp. is likely related to its specific lifestyle
Published: 2018
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146. Whole-genome landscape of Medicago truncatula symbiotic genes

Author: David Latrasse, Christine Lelandais-Brière, William Marande, Hélène Bergès, Frédéric Debellé, Stéphane Muños, Julia Buitink, Sébastien Carrère, Andreas Niebel, Mohamed Zouine, Pascal Gamas, Jonathan Kreplak, Moussa Benhamed, Olivier Bouchez, Sandra Moreau, Marie-Françoise Jardinaud, Stéphane Cauet, Thomas Blein, Jérôme Gouzy, Carine Satgé, Erika Sallet, Yann Pecrix, Céline Lopez-Roques, Margot Zahm, Baptiste Mayjonade, Aurélie Bérard, Florian Frugier, S. Evan Staton, Martin Crespi, Abdelhafid Bendahmane, Céline Chantry-Darmon, Magali Perez, Laboratoire des interactions plantes micro-organismes (LIPM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), University of British Columbia, Institut des Sciences des Plantes de Paris-Saclay (IPS2 (UMR_9213 / UMR_1403)), Institut National de la Recherche Agronomique (INRA)-Université Paris-Sud - Paris 11 (UP11)-Université Paris Diderot - Paris 7 (UPD7)-Université d'Évry-Val-d'Essonne (UEVE)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Agroécologie [Dijon], Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre National de Ressources Génomiques Végétales (CNRGV), Institut National de la Recherche Agronomique (INRA), GeT PlaGe, Genotoul, Etude du Polymorphisme des Génomes Végétaux (EPGV), Institut de Recherche en Horticulture et Semences (IRHS), Université d'Angers (UA)-Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST, ANR grants EPISYM (grant no. ANR-15-CE20-0002), NODCCAAT (no. ANR-15-CE20-0012), REGULEG (no. ANR-15-CE20-0001), the ‘Laboratoire d’Excellence (LABEX)’ TULIP (no. ANR-10-LABX-41), the LABEX Saclay Plant Sciences (SPS, no. ANR-10-LABX-40) and the European Research Council (no. ERC-SEXYPARTH), and we made use of data previously generated in the ANR SYMbiMICS (ANR-08-GENO-106) and the INRA SPE EPINOD projects. The sequencing platform was supported by France Génomique National infrastructure (grant no. ANR-10-INBS-09) and by the GET-PACBIO programme (Programme opérationnel FEDER-FSE MIDI-PYRENEES ET GARONNE 2014-2020)., Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Interactions plantes-microorganismes et santé végétale, Institut National de la Recherche Agronomique (INRA)-Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Université Paris-Sud - Paris 11 (UP11)-Université Paris Diderot - Paris 7 (UPD7)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Département de chirurgie, CRLCC Val d'Aurelle - Paul Lamarque, Génomique et Biotechnologie des Fruits (GBF), Institut National de la Recherche Agronomique (INRA)-École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Génétique Animale et Biologie Intégrative (GABI), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Génome et Transcriptome - Plateforme Génomique (GeT-PlaGe), Institut National de la Recherche Agronomique (INRA)-Plateforme Génome & Transcriptome (GET), Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire de Génétique Cellulaire (LGC), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), INRA - Mathématiques et Informatique Appliquées (Unité MIAJ), Université d'Angers (UA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-INSTITUT AGRO Agrocampus Ouest, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), ANR-15-CE20-0002,EPISYM,Régulations épigénétiques dans le développement de nodules symbiotiques racinaires chez les légumineuses(2015), ANR-15-CE20-0012,NODCCAAT,Comprendre le mode d'action du facteur de transcription NF-YA1 spécifique de l'intearction symbiotique rhizobium-légumineuses chez Medicago truncatula(2015), ANR-15-CE20-0001,REGULEG,Identification des régulateurs participant à la plasticité d'adaptation des graines de légumineuses aux changements environnementaux(2015), ANR-11-IDEX-0002,UNITI,Université Fédérale de Toulouse(2011), ANR-10-LABX-0044,CEMAM,Center of Excellence in Multifunctional Architectured Materials(2010), ANR-08-GENM-0015,SYMbiMICS,Dissection moléculaire de l'interaction symbiotique rhizobium-légumineuse : une approche combinée de micro-dissection laser et de séquençage massif d?ESTs(2008), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Institut National de la Recherche Agronomique (INRA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris-Saclay-Université Paris-Sud - Paris 11 (UP11), AGROCAMPUS OUEST-Institut National de la Recherche Agronomique (INRA)-Université d'Angers (UA), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Université de Bourgogne (UB)-Institut National de la Recherche Agronomique (INRA)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, AgroParisTech-Institut National de la Recherche Agronomique (INRA), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université d'Angers (UA)-AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut National de la Recherche Agronomique (INRA)-Université Nice Sophia Antipolis (... - 2019) (UNS), Institut National de la Recherche Agronomique (INRA)-École nationale supérieure agronomique de Toulouse (ENSAT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Institut des sciences du végétal (ISV), Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Supérieure Agronomique de Toulouse-Institut National Polytechnique (Toulouse) (Toulouse INP), Laboratoire des Interactions Plantes Micro organismes, Université Fédérale Toulouse Midi-Pyrénées, Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), UR Etude du Polymorphisme des Génomes végétaux, Centre National de Génotypage (CNG), Université Paris-Sud - Paris 11 (UP11)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Recherche Agronomique (INRA), and Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0106 biological sciences, 0301 basic medicine, Transposable element, [SDV.SA]Life Sciences [q-bio]/Agricultural sciences, [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], RNA, Untranslated, [SDV]Life Sciences [q-bio], Symbiose, Sequence assembly, Genomics, Plant Science, Computational biology, 01 natural sciences, Genome, DNA sequencing, Epigenesis, Genetic, F30 - Génétique et amélioration des plantes, 03 medical and health sciences, Genome-wide analysis of gene expression, Gene Expression Regulation, Plant, Medicago truncatula, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, Symbiosis, Gene, ComputingMilieux_MISCELLANEOUS, Plant Proteins, Rhizobial symbiosis, Whole genome sequencing, Symbiote, Génome, biology, phytogénétique, DNA Methylation, biology.organism_classification, 030104 developmental biology, RNA, Plant, Multigene Family, Next-generation sequencing, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Root Nodules, Plant, Genome, Plant, 010606 plant biology & botany
Abstract: This Whole Genome Shotgun project has been deposited at DDBJ/ENA/GenBank under the accession PSQE00000000.; Advances in deciphering the functional architecture of eukaryotic genomes have been facilitated by recent breakthroughs in sequencing technologies, enabling a more comprehensive representation of genes and repeat elements in genome sequence assemblies, as well as more sensitive and tissue-specific analyses of gene expression. Here we show that PacBio sequencing has led to a substantially improved genome assembly of Medicago truncatula A17, a legume model species notable for endosymbiosis studies1, and has enabled the identification of genome rearrangements between genotypes at a near-base-pair resolution. Annotation of the new M. truncatula genome sequence has allowed for a thorough analysis of transposable elements and their dynamics, as well as the identification of new players involved in symbiotic nodule development, in particular 1,037 upregulated long non-coding RNAs (lncRNAs). We have also discovered that a substantial proportion (~35% and 38%, respectively) of the genes upregulated in nodules or expressed in the nodule differentiation zone colocalize in genomic clusters (270 and 211, respectively), here termed symbiotic islands. These islands contain numerous expressed lncRNA genes and display differentially both DNA methylation and histone marks. Epigenetic regulations and lncRNAs are therefore attractive candidate elements for the orchestration of symbiotic gene expression in the M. truncatula genome.
Published: 2018
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147. Integrative visual omics of the white-rot fungus Polyporus brumalis exposes the biotechnological potential of its oxidative enzymes for delignifying raw plant biomass

Author: Drula, Elodie, Miyauchi, Shingo, Rancon, Anaïs, Henrissat, Bernard, Hainaut, Matthieu, Ruiz-Dueñas, F. J., Herpoël-Gimbert, Isabelle, Navarro, David, Grigoriev, Igor V., Zhou, Simeng, Raouche, Sana, Rosso, Marie-Noëlle, Alliance Nationale pour les Sciences de la Vie et de la Santé (France), European Molecular Biology Laboratory, Fondation ARC pour la Recherche sur le Cancer, France Génomique, GenoScreen, Grand Luminy Technopôle, Institut National de la Recherche Agronomique (France), Institut Paoli-Calmettes, omicX, Conseil Régional Provence-Alpes-Côte d'Azur, Département des Bouches-du-Rhône, Ville de Marseille, Drula, Elodie [0000-0002-9168-5214], Rancon, Anaïs [0000-0002-6258-0755], Henrissat, Bernard [0000-0002-3434-8588], Hainaut, Matthieu [0000-0002-7567-657X], Ruiz-Dueñas, F. J. [0000-0002-9837-5665], Herpoël-Gimbert, Isabelle [0000-0001-5518-8969], Navarro, David [0000-0002-3266-8270], Grigoriev, Igor V. [0000-0002-3136-8903], Raouche, Sana [0000-0001-5937-4902], Rosso, Marie-Noëlle https://orcid.org/0000-0001-8317-7220, Drula, Elodie, Rancon, Anaïs, Henrissat, Bernard, Hainaut, Matthieu, Ruiz-Dueñas, F. J., Herpoël-Gimbert, Isabelle, Navarro, David, Grigoriev, Igor V., and Raouche, Sana
Subjects: Fungal adaptive response to lignocellulose
Abstract: 3 p. Jérémy Tournayre, Laurent Parry, Anne-Catherine Maurin, Julien Averous, Alain Bruhat, et al.. Identification de marques épigénétiques marqueurs de prédisposition aux maladies métaboliques. JOBIM 2018 Journées Ouvertes Biologie, Informatique et Mathématiques, Jul 2018, Marseille, France. ffhal-01930383f
Published: 2018

148. Diversification of human plasmacytoid predendritic cells in response to a single stimulus

Author: Solana G. Alculumbre, Michel Gilliet, Mathieu Maurin, Mabel San Roman, Benjamin Terrier, Pablo Vargas, Paolo Maiuri, Vassili Soumelis, Curdin Conrad, Pierre Bost, David Saadoun, Philémon Sirven, Jeremy Di Domizio, Antonin Morillon, Léa Savey, Maxime Wery, Maxime Touzot, Violaine Saint-André, Alculumbre, Sg, Saint-Andre, V, Di Domizio, J, Vargas, P, Sirven, P, Bost, P, Maurin, M, Maiuri, P, Wery, M, San Roman, M, Savey, L, Touzot, M, Terrier, B, Saadoun, D, Conrad, C, Gilliet, M, Morillon, A, Soumelis, V, Immunité et cancer (U932), Institut Curie-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Dynamique de l'information génétique : bases fondamentales et cancer (DIG CANCER), Institut Curie-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunité et cancer, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie, Laboratory of Molecular Virology, International Centre for Genetic Engineering and Biotechnology (ICGEB), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie-Centre National de la Recherche Scientifique (CNRS), Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], AURA Paris - Plaisance, CHU Cochin [AP-HP], Immunologie - Immunopathologie - Immunothérapie (I3), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Immunologie Clinique, Institut Curie, Institut Curie-Institut Curie, Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Sorbonne Université (SU), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Biologie Cellulaire et Cancer, Institut Curie [Paris]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL), Institut Curie [Paris], IFOM, Istituto FIRC di Oncologia Molecolare (IFOM), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Université Pierre et Marie Curie - Paris 6 (UPMC), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] (DHU - I2B), Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre National de Référence Maladies Systémiques et Autoimmunes Rares, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CIC1428 IGR-CURIE, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by funding from INSERM (BIO2014-08), FRM, ANR-13-BSV1-0024-02, ANR-10-IDEX-0001-02 PSL* and ANR-11-LABX-0043, ERC (IT-DC 281987, HEALTH 2011-261366 and 2013/COG/616180 DARK) and CIC IGR-Curie 1428. S.G.A. was supported by an IC fellowship and LabEx DCbiol. V.S-A. is supported as a Fondation pour la Recherche Médicale fellow (ARF20150934193). High-throughput sequencing was performed by the ICGex NGS platform of the Institut Curie, supported by grants ANR-10-EQPX-03 (Equipex) and ANR-10-INBS-09-08 (France Génomique Consortium) from the Agence Nationale de la Recherche (‘Investissements d’Avenir’ program), by the Canceropole Ile-de-France and by the SiRIC-Curie program, SiRIC Grant INCa-DGOS-4654., We thank the Cytometry Core facility of IC for cell sorting. We thank INSERM U932, particularly P. Michea, for frequent discussions. We thank S. Amigorena, N. Manel and L. Pattarini for critical reading of the manuscript., ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), ANR-10-EQPX-0003,ICGex,Equipement de biologie intégrative du cancer pour une médecine personnalisée(2010), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Université Paris Descartes - Paris 5 (UPD5)-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, medicine.medical_treatment, Immunology, Gene Expression, Adaptive Immunity, Biology, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, B7-H1 Antigen, 03 medical and health sciences, 0302 clinical medicine, Immune system, Microscopy, Electron, Transmission, medicine, Humans, Lupus Erythematosus, Systemic, Psoriasis, Immunology and Allergy, Autocrine signalling, Cells, Cultured, ComputingMilieux_MISCELLANEOUS, Innate immune system, Gene Expression Profiling, hemic and immune systems, Dendritic Cells, Orthomyxoviridae, Acquired immune system, Type I interferon production, Immunity, Innate, Cell biology, 030104 developmental biology, Cytokine, Interferon Type I, B7-1 Antigen, Cytokines, Interferon type I, CD80, 030215 immunology, medicine.drug
Abstract: Comment in : Plasmacytoid dendritic cells: Division of labour./ Bird L. Nat Rev Immunol. 2017 Dec 22;18(1):2-3. doi: 10.1038/nri.2017.153. PMID: 29269763; International audience; Innate immune cells adjust to microbial and inflammatory stimuli through a process termed environmental plasticity, which links a given individual stimulus to a unique activated state. Here, we report that activation of human plasmacytoid predendritic cells (pDCs) with a single microbial or cytokine stimulus triggers cell diversification into three stable subpopulations (P1-P3). P1-pDCs (PD-L1+CD80-) displayed a plasmacytoid morphology and specialization for type I interferon production. P3-pDCs (PD-L1-CD80+) adopted a dendritic morphology and adaptive immune functions. P2-pDCs (PD-L1+CD80+) displayed both innate and adaptive functions. Each subpopulation expressed a specific coding- and long-noncoding-RNA signature and was stable after secondary stimulation. P1-pDCs were detected in samples from patients with lupus or psoriasis. pDC diversification was independent of cell divisions or preexisting heterogeneity within steady-state pDCs but was controlled by a TNF autocrine and/or paracrine communication loop. Our findings reveal a novel mechanism for diversity and division of labor in innate immune cells.
Published: 2018
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149. Virome analysis of two sympatric bat species (Desmodus rotundus and Molossus molossus) in French Guiana

Author: LACOSTE, Vincent, SALMIER, Arielle, TIRERA, Sourakhata, FRANC, Alain, DARCISSAC, Edith, DONATO, Damien, BOUCHIER, Christiane, LAVERGNE, Anne, DE THOISY, Benoit, FORRESTER, Naomi, Laboratoire des Interactions Virus-Hôtes [Cayenne, Guyane Française], Institut Pasteur de la Guyane, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Biodiversité, Gènes & Communautés (BioGeCo), Institut National de la Recherche Agronomique (INRA)-Université de Bordeaux (UB), from patterns to models in computational biodiversity and biotechnology (PLEIADE), Laboratoire Bordelais de Recherche en Informatique (LaBRI), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Biodiversité, Gènes & Communautés (BioGeCo), Institut National de la Recherche Agronomique (INRA)-Université de Bordeaux (UB)-Institut National de la Recherche Agronomique (INRA), Génomique (Plate-Forme) - Genomics Platform, Institut Pasteur [Paris], A. Salmier was funded by a grant from European funds (PO FSE 2007-2013) and 'Investissement d’Avenir' managed by Agence Nationale de la Recherche (CEBA, Ref. ANR-10-LABEX-25-01). This study was conducted within the CAROLIA program supported by European funds (ERDF/FEDER) and assistance from Région Guyane and Direction Régionale pour la Recherche et la Technologie. It also received a European Commission 'REGPOT-CT-2011-285837-STRonGer' grant within the FP7 and 'Investissement d’Avenir' grants managed by the Agence Nationale de la Recherche (CEBA, Ref. ANR-10-LABEX-25-01). The Genomics Platform is a member of the France Génomique consortium (ANR10-INBS-09-08)., We acknowledge François Catzeflis and Marguerite Delaval for useful discussions on the biology, ecology and dynamics of bats. All field volunteers and owners and/or managers of capture sites are warmly acknowledged for their assistance in captures. We thank the INDA and C3BI teams at the Institut Pasteur and UMR BIOGECO for their technical support and access to the clusters. We thank L. Ma and M. Tichit for technical assistance., ANR-10-LABX-0025,CEBA,CEnter of the study of Biodiversity in Amazonia(2010), Université de Bordeaux (UB)-Institut National de la Recherche Agronomique (INRA), Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Université Sciences et Technologies - Bordeaux 1-Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Université Sciences et Technologies - Bordeaux 1-Université Bordeaux Segalen - Bordeaux 2-Inria Bordeaux - Sud-Ouest, Université de Bordeaux (UB)-Institut National de la Recherche Agronomique (INRA)-Université de Bordeaux (UB)-Institut National de la Recherche Agronomique (INRA), Génomique (Plate-Forme), ANR-10-LABX-25-01/10-LABX-0025,CEBA,CEnter of the study of Biodiversity in Amazonia(2010), Université de Bordeaux (UB)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Centre National de la Recherche Scientifique (CNRS)-Inria Bordeaux - Sud-Ouest, and Institut Pasteur [Paris] (IP)
Subjects: Topography, Molossus molossus, Forests, [SDV.BID.SPT]Life Sciences [q-bio]/Biodiversity/Systematics, Phylogenetics and taxonomy, Pathology and Laboratory Medicine, amazonie, Chiroptera, Bats, MESH: Animals, MESH: Ecosystem, lcsh:Science, MESH: Phylogeny, Phylogeny, Mammals, Fruit Bats, Eukaryota, Phylogenetic Analysis, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Terrestrial Environments, French Guiana, Sympatric speciation, Medical Microbiology, Viral Pathogens, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: Viruses/genetics, MESH: Metagenomics, Bioinformatics, 030106 microbiology, Zoology, Sequence Databases, hématophage, Microbiology, 03 medical and health sciences, Phylogenetics, MESH: Sympatry/genetics, forêt primaire, espèce réservoir, Evolutionary Systematics, Saliva, Microbial Pathogens, Ecosystem, Host (biology), lcsh:R, Ecology and Environmental Sciences, Organisms, Biology and Life Sciences, 15. Life on land, 030104 developmental biology, desmodus rotundus, lcsh:Q, Metagenomics, 0301 basic medicine, MESH: Genome, Viral/genetics, Insecta, Range (biology), Physiology, viruses, MESH: Insecta/virology, lcsh:Medicine, Database and Informatics Methods, Medicine and Health Sciences, MESH: Chiroptera/virology, Data Management, Multidisciplinary, Ecology, MESH: Insect Viruses/genetics, Body Fluids, Sympatry, Caves, Viruses, Vertebrates, Anatomy, Pathogens, épidémie, Sequence Analysis, Research Article, Computer and Information Sciences, Herpesviruses, Insect Viruses, Genome, Viral, Biology, Research and Analysis Methods, Ecosystems, néotropique, chauve souris, MESH: Chiroptera/genetics, MESH: French Guiana, Animals, Human virome, population virale, Taxonomy, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, Evolutionary Biology, Landforms, insectivore, Insectivore, Geomorphology, biology.organism_classification, MESH: Sympatry/physiology, Biological Databases, Amniotes, Desmodus rotundus, Earth Sciences, DNA viruses
Abstract: International audience; Environmental disturbances in the Neotropics (e.g., deforestation, agriculture intensifica-tion, urbanization) contribute to an increasing risk of cross-species transmission of microorganisms and to disease outbreaks due to changing ecosystems of reservoir hosts. Although Amazonia encompasses the greatest diversity of reservoir species, the outsized viral population diversity (virome) has yet to be investigated. Here, through a metagenomic approach, we identified 10,991 viral sequences in the saliva and feces of two bat species, Desmodus rotundus (hematophagous), trapped in two different caves surrounded by primary lowland forest, and Molossus molossus (insectivorous), trapped in forest and urban habitats. These sequences are related to 51 viral families known to infect a wide range of hosts (i.e., bacteria , plants, insects and vertebrates). Most viruses detected reflected the diet of bat species, with a high proportion of plant and insect-related viral families for M. molossus and a high proportion of vertebrate-related viral families for D. rotundus, highlighting its influence in shaping the viral diversity of bats. Lastly, we reconstructed the phylogenetic relationships for five vertebrate-related viral families (Nairoviridae, Circoviridae, Retroviridae, Herpesviri-dae, Papillomaviridae). The results showed highly supported clustering with other viral sequences of the same viral family hosted by other bat species, highlighting the potential association of viral diversity with the host's diet. These findings provide significant insight into viral bat diversity in French Guiana belonging to the Amazonian biome and emphasize that habitats and the host's dietary ecology may drive the viral diversity in the bat communities investigated.
Published: 2017
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150. Diverse laboratory colonies ofAedes aegyptiharbor the same adult midgut bacterial microbiome

Author: Anubis Vega-Rúa, Martin N. Mayanja, Isabelle Dusfour, Veasna Duong, Alain Kohl, Christophe Paupy, Christiane Bouchier, Amine Ghozlane, Laura B. Dickson, Stevenn Volant, Louis Lambrechts, Julius J. Lutwama, Laurence Ma, Davy Jiolle, Interactions Virus-Insectes - Insect-Virus Interactions (IVI), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Centre de Recherche et Innovation Technologique (CITECH), Institut Pasteur [Paris] (IP), Institut Pasteur de la Guadeloupe, Réseau International des Instituts Pasteur (RIIP), Institut Pasteur de la Guyane, Diversity, ecology, evolution & Adaptation of arthropod vectors (MIVEGEC-DEEVA), Evolution des Systèmes Vectoriels (ESV), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Centre International de Recherches Médicales de Franceville (CIRMF), Uganda Virus Research Institute, Entebbe, Uganda, MRC - University of Glasgow Centre for Virus Research, Institut Pasteur du Cambodge, This work was supported by Agence Nationale de la Recherche (grants ANR-16-CE35-0004-01 and ANR-17-ERC2-0016-01 to LL), the French Government’s Investissement d’Avenir program Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases (grant ANR-10-LABX-62-IBEID to LL), the City of Paris Emergence(s) program in Biomedical Research (to LL), the European Union’s Horizon 2020 research and innovation programme under ZikaPLAN grant agreement No 734584 (to LL), the European Union and Guadeloupe Region (Programme Opérationnel FEDER-Guadeloupe-Conseil Régional 2014-2020, grant 2015-FED-192 to AVR) and the United Kingdom Medical Research Council (grant MC_UU_12014 to AK). The Genomics Facility is a member of the 'France Génomique' consortium (grant ANR10-INBS-09-08 to CB). The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication., We are grateful to Gordana Rašić and Ary Hoffmann for providing the mosquito colony from Cairns and to Borin Peng for the mosquito collection in Phnom Penh. We thank Claire Valiente Moro, Guillaume Minard and the Lambrechts lab members for their insights., ANR-16-CE35-0004,MOSQUIBIOTA,Contribution de la diversité bactérienne intestinale à la capacité vectorielle d'Aedes aegypti(2016), ANR-17-ERC2-0016,GxG,Base génétique de la spécificité génotype-génotype dans l'interaction naturelle entre un virus et son insecte vecteur(2017), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 734584,ZikaPLAN, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris]
Subjects: 0301 basic medicine, 0106 biological sciences, Range (biology), [SDV]Life Sciences [q-bio], 030106 microbiology, Zoology, Human pathogen, Aedes aegypti, Gut flora, DNA, Ribosomal, digestive system, 010603 evolutionary biology, 01 natural sciences, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, Mosquito, Aedes, RNA, Ribosomal, 16S, Animals, Cluster Analysis, lcsh:RC109-216, Microbiome, Phylogeny, 030304 developmental biology, 0303 health sciences, Genetic diversity, Bacteria, biology, Ecology, Research, Microbiota, fungi, Midgut, Sequence Analysis, DNA, biology.organism_classification, Vectorial capacity, Gastrointestinal Microbiome, Gastrointestinal Tract, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, 030104 developmental biology, Infectious Diseases, Parasitology, Metagenomics
Abstract: BackgroundHost-associated microbes, collectively known as the microbiota, play an important role in the biology of multicellular organisms. In mosquito vectors of human pathogens, the gut bacterial microbiota influences vectorial capacity and has become the subject of intense study. In laboratory studies of vector biology, genetic effects are often inferred from differences between geographically and genetically diverse colonies of mosquitoes that are reared in the same insectary. It is unclear, however, to what extent genetic effects can be confounded by uncontrolled differences in the microbiota composition among mosquito colonies. To address this question, we used 16S metagenomics to compare the midgut bacterial microbiome of six recent laboratory colonies ofAedes aegyptirepresenting the geographical range and genetic diversity of the species.ResultsWe found that the diversity, abundance, and community structure of the midgut bacterial microbiome was remarkably similar among the six different colonies ofAe. aegypti, regardless of their geographic origin. We also confirmed the relatively low complexity of bacterial communities inhabiting the mosquito midgut.ConclusionsOur finding that geographically diverse colonies ofAe. aegyptireared in the same insectary harbor a similar gut bacterial microbiome supports the conclusion that the gut microbiota of adult mosquitoes is environmentally determined regardless of the host genotype. Thus, uncontrolled differences in microbiota composition are unlikely to represent a significant confounding factor in genetic studies of vector biology.
Published: 2017
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