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5 results on '"SIRIC OncoLille (Grant INCa-DGOS-Inserm) [6041]"'

1. The out-of-field dose in radiation therapy induces delayed tumorigenesis by senescence evasion

Author

Erwan Goy, Maxime Tomezak, Caterina Facchin, Nathalie Martin, Emmanuel Bouchaert, Jerome Benoit, Clementine de Schutter, Joe Nassour, Laure Saas, Claire Drullion, Priscille M Brodin, Alexandre Vandeputte, Olivier Molendi-Coste, Laurent Pineau, Gautier Goormachtigh, Olivier Pluquet, Albin Pourtier, Fabrizio Cleri, Eric Lartigau, Nicolas Penel, Corinne Abbadie, Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), 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), Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520 (IEMN), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-JUNIA (JUNIA), Université catholique de Lille (UCL)-Université catholique de Lille (UCL), Oncovet Clinical Research [Loos] (Eurasanté - OCR), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Réseau International des Instituts Pasteur (RIIP), Physique - IEMN (PHYSIQUE - IEMN), Université catholique de Lille (UCL)-Université catholique de Lille (UCL)-Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-JUNIA (JUNIA), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, This work was supported by the Centre National de la Recherche Scientifique, the Université de Lille, the Ligue contre le Cancer (Comité du Pas-de-Calais, Comité de la Somme, Comité du Nord), the Cancéropole Nord-Ouest, the Institut Pasteur de Lille, the SIRIC OncoLille (Grant INCa-DGOS-Inserm 6041), the Agence Nationale de Recherche (ANR-10-EQPX-04-01), the Feder (12001407 [D-AL]), and the Contrat de Plan Etat Région CPER Cancer 2015-2020. EG had a fellowship from the Institut Pasteur de Lille and the Région Hauts-de-France. MT had a fellowship from the Université de Lille. CF had a fellowship from the European Erasmus program. JN had fellowships from the Université de Lille and from the Association pour la Recherche sur le Cancer. LS and CD had fellowships from the Région Hauts-de-France. We thank Thomas Lacornerie for giving access to the Varian CLINAC and for performing dose profiles. We thank the Bioimaging Center Lille-Nord de France (Campus Calmette), especially Antonino Bongiovanni and Hélène Bauderlique, for imaging and cytometry facilities. We thank the PLETHA animal facility, especially Thierry Chassat and David Hannebique. We thank David Dombrowicz for giving access to the BD Influx (Becton Dickinson). We thank Benoit Vatrinet, Anaïs Engrand, and Olivier Samyn for technical help. The authors have no conflicting financial interests., FundingLigue Contre le CancerCorinne AbbadieSIRIC Oncolille (INCa-DGOS-Inserm 6041)Corinne AbbadieAgence Nationale de la Recherche (ANR-10-EQPX-04-01)Priscille M BrodinFeder (12001407 (D-AL))Priscille M BrodinInstitut Pasteur de Lille, France (PhD student Fellowship)Erwan GoyRegion des Hauts-de-France, France (PhD student Fellowship)Erwan GoyEuropean Erasmus Program (Graduate student Fellowship)Caterina FacchinFondation ARC pour la Recherche sur le Cancer (PhD student Fellowship)Joe NassourRegion des Hauts-de-France (Engineer Fellowship)Laure SaasRegion des Hauts-de-France (Post-doctoral Fellowship)Claire Drullion, and CLERI, FABRIZIO

Subjects
DNA Repair, General Immunology and Microbiology, Carcinogenesis, General Neuroscience, Neoplasms, Second Primary, [SDV.CAN]Life Sciences [q-bio]/Cancer, General Medicine, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, General Biochemistry, Genetics and Molecular Biology, [SDV.IB.MN] Life Sciences [q-bio]/Bioengineering/Nuclear medicine, Mice, Cell Transformation, Neoplastic, [SDV.CAN] Life Sciences [q-bio]/Cancer, Animals, DNA Breaks, Single-Stranded, Cellular Senescence, DNA Damage
Abstract

International audience; A rare but severe complication of curative-intent radiation therapy is the induction of second primary cancers. These cancers preferentially develop not inside the planning target volume (PTV) but around, over several centimeters, after a latency period of 1–40 years. We show here that normal human or mouse dermal fibroblasts submitted to the out-of-field dose scattering at the margin of a PTV receiving a mimicked patient’s treatment do not die but enter in a long-lived senescent state resulting from the accumulation of unrepaired DNA single-strand breaks, in the almost absence of double-strand breaks. Importantly, a few of these senescent cells systematically and spontaneously escape from the cell cycle arrest after a while to generate daughter cells harboring mutations and invasive capacities. These findings highlight single-strand break-induced senescence as the mechanism of second primary cancer initiation, with clinically relevant spatiotemporal specificities. Senescence being pharmacologically targetable, they open the avenue for second primary cancer prevention.

Published
2022

2. The Profile of Emotional Competence (PEC): A French short version for cancer patients

Author

Anne-Sophie Baudry, Veronique Christophe, Emilie Constant, Guillaume Piessen, Amelie Anota, FREGAT Working Group, Pôle Cancérologie et Spécialités Médicales [Valenciennes], Centre hospitalier [Valenciennes, Nord], Sciences Cognitives et Sciences Affectives (SCALab) - UMR 9193 (SCALab), Université de Lille-Centre National de la Recherche Scientifique (CNRS), French National Platform Quality of Life and Cancer, Human and Social Sciences Department [Lyon], Centre Léon Bérard [Lyon], Department of Digestive and Oncological Surgery [Lille], Hôpital Claude Huriez [Lille], CHU Lille-CHU Lille-Université de Lille, Unité de Méthodologie et de Qualité de Vie en Cancérologie (UMQVC), Institut Régional Fédératif du Cancer (IRFC)-Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Pôle cancérologie (CHRU Besançon), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), This work was supported by the SIRIC ONCOLille (Grant INCa-DGOS Inserm 6041) to VC and the 'Region Hauts-de-France.' FREGAT was funded with support from the French National Cancer Institute (INCa) and the CHU de Lille is the sponsor of the FREGAT study., FREGAT Working Group, Laboratoire Sciences Cognitives et Sciences Affectives - UMR 9193 (SCALab), Plateforme nationale qualité de vie et cancer, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Institut Régional Fédératif du Cancer (IRFC), and Bodescot, Myriam

Subjects
Questionnaires, Male, Psychometrics, Emotions, [SDV.NEU.PC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Social Sciences, 050109 social psychology, Anxiety, Emotional competence, Mathematical and Statistical Techniques, 0302 clinical medicine, Neoplasms, Item response theory, Medicine and Health Sciences, Psychology, Aged, 80 and over, Multidisciplinary, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, Depression, Statistics, 05 social sciences, Middle Aged, Prognosis, 3. Good health, Research Design, 030220 oncology & carcinogenesis, Physical Sciences, Medicine, Female, medicine.symptom, Factor Analysis, Research Article, Clinical psychology, Intrapersonal communication, Adult, Psychological Adjustment, Science, [SDV.CAN]Life Sciences [q-bio]/Cancer, Emotional Adjustment, Research and Analysis Methods, 03 medical and health sciences, Quality of life (healthcare), [SDV.CAN] Life Sciences [q-bio]/Cancer, Mental Health and Psychiatry, medicine, Humans, Interpersonal Relations, 0501 psychology and cognitive sciences, Statistical Methods, Aged, Survey Research, Mood Disorders, Biology and Life Sciences, Polytomous Rasch model, Confidence interval, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Quality of Life, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Self Report, Mathematics
Abstract

BackgroundIntrapersonal and interpersonal Emotional Competence (EC) predicts better health and disease adjustment. This study aimed to validate a short version of the Profile of Emotional Competence (PEC) scale for cancer patients.MethodsFive hundred and thirty-five patients with cancer completed a self-reported questionnaire assessing their intra- and interpersonal EC (PEC), their anxiety and depression symptoms (HADS), and their health-related quality of life (QLQ-C30). Confirmatory factor analyses and Item Response Theory models with the Partial Credit Model were performed to validate and reduce the scale.FindingsThe Short-PEC (13 items), composed of 2 sub-scores of intra- (6 items) and interpersonal (7 items) EC, showed an improved factorial structure (Root Mean Square Error of Approximation (RMSEA) = 0.075 (90% confidence interval 0.066-0.085), comparative fit index = 0.915) with good psychometric properties.DiscussionFuture studies should use the Short-PEC to explain and predict the adjustment of cancer patients. The short-PEC could be also used in clinical routine to assess the level of EC of patients and to adapt psychosocial intervention.

Published
2020

3. Vidjil: A Web Platform for Analysis of High-Throughput Repertoire Sequencing

Author

Mikaël Salson, Ryan Herbert, Marc Duez, Mathieu Giraud, Florian Thonier, Tatiana Rocher, Site de Recherche Intégrée en Cancérologie ( SIRIC-ONCOLille ), Université de Lille, Sciences et Technologies-Université de Lille, Sciences Humaines et Sociales-CRLCC Oscar Lambret-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), School of Social and Community Medicine [Bristol], University of Bristol [Bristol], Centre de Recherche en Informatique, Signal et Automatique de Lille (CRIStAL) - UMR 9189 ( CRIStAL ), Institut National de Recherche en Informatique et en Automatique ( Inria ) -Ecole Centrale de Lille-Institut Mines-Télécom [Paris]-Université de Lille-Centre National de la Recherche Scientifique ( CNRS ), 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 (CRIStAL) - UMR 9189 ( CRIStAL ), Institut National de Recherche en Informatique et en Automatique ( Inria ) -Ecole Centrale de Lille-Institut Mines-Télécom [Paris]-Université de Lille-Centre National de la Recherche Scientifique ( CNRS ) -Ecole Centrale de Lille-Institut Mines-Télécom [Paris]-Université de Lille-Centre National de la Recherche Scientifique ( CNRS ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Necker Enfants-Malades (INEM) ( INEM - UM 111 (UMR 8253 / U1151) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), SIRIC ONCOLille, Grant INCa-DGOS-Inserm 6041, Fondation EDF, Site de Recherche Intégrée en Cancérologie (SIRIC-ONCOLille), Université de Lille, Sciences et Technologies-Université de Lille, Sciences Humaines et Sociales-Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), 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), Bioinformatics and Sequence Analysis (BONSAI), Centre National de la Recherche Scientifique (CNRS)-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)-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), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), 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 de Lille-UNICANCER-Université de Lille-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), 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), and Salson, Mikaël

Subjects
0301 basic medicine, lymphocytes, Source code, [INFO.INFO-DS] Computer Science [cs]/Data Structures and Algorithms [cs.DS], Repertoire sequencing RepSeq, computer.software_genre, Computer Applications, Software-aided sequence analysis, Hematologic Cancers and Related Disorders, Database and Informatics Methods, White Blood Cells, 0302 clinical medicine, Animal Cells, Medicine and Health Sciences, VDJ recombinations, computer.programming_language, media_common, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], Genetics, education.field_of_study, Multidisciplinary, Applied Mathematics, Simulation and Modeling, Acute lymphoblastic leukaemia, Hematology, Acute Lymphoblastic Leukemia, 3. Good health, Physical sciences, Oncology, Web-Based Applications, Lymphoblastic Leukemia, computer software, Medicine, The Internet, Cellular Types, Sequence Analysis, Algorithms, Research Article, FASTQ format, Computer and Information Sciences, Web server, Bioinformatics, Immune Cells, media_common.quotation_subject, Science, Immunology, Population, [INFO.INFO-DS]Computer Science [cs]/Data Structures and Algorithms [cs.DS], Sequence Databases, Biology, Research and Analysis Methods, JavaScript, 03 medical and health sciences, [ INFO.INFO-BI ] Computer Science [cs]/Bioinformatics [q-bio.QM], Leukemias, Web application, Molecular Biology Techniques, Sequencing Techniques, education, Molecular Biology, web-based application, BLAST algorithm, [ INFO.INFO-DS ] Computer Science [cs]/Data Structures and Algorithms [cs.DS], Blood Cells, business.industry, Biology and Life Sciences, Cancers and Neoplasms, Cell Biology, Python (programming language), Biological Databases, 030104 developmental biology, Operating system, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], business, Sequence Alignment, computer, Mathematics, 030215 immunology
Abstract

International audience; BackgroundThe B and T lymphocytes are white blood cells playing a key role in the adaptive immunity. A part of their DNA, called the V(D)J recombinations, is specific to each lymphocyte, and enables recognition of specific antigenes. Today, with new sequencing techniques, one can get billions of DNA sequences from these regions. With dedicated Repertoire Sequencing (RepSeq) methods, it is now possible to picture population of lymphocytes, and to monitor more accurately the immune response as well as pathologies such as leukemia.Methods and ResultsVidjil is an open-source platform for the interactive analysis of high-throughput sequencing data from lymphocyte recombinations. It contains an algorithm gathering reads into clonotypes according to their V(D)J junctions, a web application made of a sample, experiment and patient database and a visualization for the analysis of clonotypes along the time. Vidjil is implemented in C++, Python and Javascript and licensed under the GPLv3 open-source license. Source code, binaries and a public web server are available at http://www.vidjil.org and at http://bioinfo.lille.inria.fr/vidjil. Using the Vidjil web application consists of four steps: 1. uploading a raw sequence file (typically a FASTQ); 2. running RepSeq analysis software; 3. visualizing the results; 4. annotating the results and saving them for future use. For the end-user, the Vidjil web application needs no specific installation and just requires a connection and a modern web browser. Vidjil is used by labs in hematology or immunology for research and clinical applications.

Published
2016

4. ATF6 alpha regulates morphological changes associated with senescence in human fibroblasts

Author

Christian Slomianny, Ludovic Huot, Chantal Vercamer, Nathalie Martin, David Hot, Albin Pourtier, Julie Desle, Laure Saas, Olivier Pluquet, Clémentine Druelle, Eric Chevet, Nicolas Malaquin, Johanna Cormenier, Corinne Abbadie, Claire Drullion, Fatima Bouali, Institut de biologie de Lille - IBL (IBLI), Université de Lille, Sciences et Technologies-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), 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), Laboratoire de Physiologie Cellulaire : Canaux ioniques, inflammation et cancer - U 1003 (PHYCELL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Plateforme d'expertises génomiques appliquées aux sciences expérimentales [Lille] (PEGASE-Biosciences), Institut Pasteur de Lille, Oncogenesis Stress Signaling (OSS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CRLCC Eugène Marquis (CRLCC), CRLCC Eugène Marquis (CRLCC), Université de Lille, Droit et Santé, Centre National de la Recherche Scientifique, Universite Lille 1, Ligue Nationale contre le Cancer, Association pour la Recherche sur le Cancer, Universite Lille 2, Ligue contre le Cancer, SIRIC OncoLille (Grant INCa-DGOS-Inserm) [6041], fellowship 'Accueil Jeune chercheur' from Region Nord-Pas-de-Calais, fellowship from 'Relations Internationales' of University Lille 1, fellowship from Region Nord-Pas-de-Calais/CNRS, 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), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC), and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Droit et Santé

Subjects
0301 basic medicine, Senescence, Adult, Male, endoplasmic-reticulum stress, senescence, Cellular senescence, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, er stress, medicine.disease_cause, Endoplasmic Reticulum, Dermal fibroblast, 03 medical and health sciences, Research Paper: Gerotarget (Focus on Aging), Microscopy, Electron, Transmission, medicine, Humans, cellular senescence, Cell shape, normal human dermal fibroblast, Child, membrane, Cells, Cultured, disease, Gerotarget, pathway, Gene Expression Profiling, Infant, cytoskeleton, Dermis, unfolded protein response, Fibroblasts, ATF6α, Endoplasmic Reticulum Stress, gene-expression, 3. Good health, Cell biology, Activating Transcription Factor 6, 030104 developmental biology, Oncology, Unfolded protein response, cells, Female, RNA Interference, Carcinogenesis, Signal Transduction
Abstract

// Clementine Druelle 1,6,* , Claire Drullion 1,* , Julie Desle 1,* , Nathalie Martin 1 , Laure Saas 1 , Johanna Cormenier 1 , Nicolas Malaquin 1,7 , Ludovic Huot 2 , Christian Slomianny 3 , Fatima Bouali 1 , Chantal Vercamer 1 , David Hot 2 , Albin Pourtier 1 , Eric Chevet 4,5 , Corinne Abbadie 1 and Olivier Pluquet 1 1 Universite de Lille, Institut Pasteur de Lille, CNRS UMR8161, Mechanisms of Tumourigenesis and Targeted Therapies, Lille, France 2 Universite de Lille, Institut Pasteur de Lille, INSERM, CNRS UMR8204, Centre d’Infection et d’Immunite de Lille, Lille, France 3 Universite de Lille, INSERM U1003, Villeneuve d’Ascq, France 4 Oncogenesis, Stress, Signaling, INSERM ER-440 Universite de Rennes, Rennes, France 5 Centre de Lutte Contre le Cancer Eugene Marquis, Rennes, France 6 Department of Anatomy and Neuroscience, Biosciences Institute, University College Cork, Cork, Ireland 7 Institut du Cancer de Montreal, Montreal, QC, Canada * These authors have contributed equally to this work Correspondence to: Olivier Pluquet, email: // Keywords : senescence, unfolded protein response, ATF6α, endoplasmic reticulum, normal human dermal fibroblast, Gerotarget Received : June 22, 2016 Accepted : August 02, 2016 Published : August 22, 2016 Abstract Cellular senescence is known as an anti-tumor barrier and is characterized by a number of determinants including cell cycle arrest, senescence associated β-galactosidase activity and secretion of pro-inflammatory mediators. Senescent cells are also subjected to enlargement, cytoskeleton-mediated shape changes and organelle alterations. However, the underlying molecular mechanisms responsible for these last changes remain still uncharacterized. Herein, we have identified the Unfolded Protein Response (UPR) as a player controlling some morphological aspects of the senescent phenotype. We show that senescent fibroblasts exhibit ER expansion and mild UPR activation, but conserve an ER stress adaptive capacity similar to that of exponentially growing cells. By genetically invalidating the three UPR sensors in senescent fibroblasts, we demonstrated that ATF6α signaling dictates senescence-associated cell shape modifications. We also show that ER expansion and increased secretion of the pro-inflammatory mediator IL6 were partly reversed by silencing ATF6α in senescent cells. Moreover, ATF6α drives the increase of senescence associated-β-galactosidase activity. Collectively, these findings unveil a novel and central role for ATF6α in the establishment of morphological features of senescence in normal human primary fibroblasts.

Published
2016

5. Fast multiclonal clusterization of V(D)J recombinations from high-throughput sequencing

Author

Céline Villenet, Mikaël Salson, Mathieu Giraud, Nathalie Grardel, Christophe Roumier, Marc Duez, Martin Figeac, Sabine Quief, Aurélie Caillault, Claude Preudhomme, Giraud, Mathieu, Laboratoire d'Informatique Fondamentale de Lille (LIFL), Université de Lille, Sciences et Technologies-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lille, Sciences Humaines et Sociales-Centre National de la Recherche Scientifique (CNRS), Bioinformatics and Sequence Analysis (BONSAI), Université de Lille, Sciences et Technologies-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lille, Sciences Humaines et Sociales-Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Sciences et Technologies-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lille, Sciences Humaines et Sociales-Centre National de la Recherche Scientifique (CNRS)-Inria Lille - Nord Europe, Institut National de Recherche en Informatique et en Automatique (Inria), Site de Recherche Intégrée en Cancérologie (SIRIC-ONCOLille), Université de Lille, Sciences et Technologies-Université de Lille, Sciences Humaines et Sociales-Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER-Université de Lille-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Plateforme de génomique fonctionnelle et structurelle [Lille], Institut pour la recherche sur le cancer de Lille [Lille] (IRCL)-Université de Lille, Droit et Santé, Institut pour la recherche sur le cancer de Lille [Lille] (IRCL), Service d'Hématologie Cellulaire [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut de recherche sur le cancer, Institut National de la Santé et de la Recherche Médicale (INSERM), Research supported by SIRIC ONCOLille (Grant INCa-DGOS-Inserm 6041) and by Région Nord-Pas-de-Calais (ABILES), Vidjil - http://www.vidjil.org, and Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER-Cancéropole Nord-Ouest-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)

Subjects
clone (Java method), Neoplasm, Residual, [SDV.IMM] Life Sciences [q-bio]/Immunology, Sequence analysis, Repertoire sequencing (Rep-Seq), Immunology, [SDV.GEN] Life Sciences [q-bio]/Genetics, Biology, Germline, DNA sequencing, 03 medical and health sciences, 0302 clinical medicine, medicine, Genetics, Humans, Repertoire sequencing, [INFO.INFO-DL]Computer Science [cs]/Digital Libraries [cs.DL], V(D)J recombinations, 030304 developmental biology, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], 0303 health sciences, [SDV.GEN]Life Sciences [q-bio]/Genetics, High-throughput sequencing, Leukemia, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Methodology Article, V(D)J recombination, Minimal residual disease follow-up, High-Throughput Nucleotide Sequencing, Sequence Analysis, DNA, Precursor Cell Lymphoblastic Leukemia-Lymphoma, medicine.disease, Minimal residual disease, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], V(D)J Recombination, [SDV.IMM]Life Sciences [q-bio]/Immunology, DNA microarray, [INFO.INFO-DL] Computer Science [cs]/Digital Libraries [cs.DL], [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Algorithms, Software, 030215 immunology, Biotechnology
Abstract

Background V(D)J recombinations in lymphocytes are essential for immunological diversity. They are also useful markers of pathologies. In leukemia, they are used to quantify the minimal residual disease during patient follow-up. However, the full breadth of lymphocyte diversity is not fully understood. Results We propose new algorithms that process high-throughput sequencing (HTS) data to extract unnamed V(D)J junctions and gather them into clones for quantification. This analysis is based on a seed heuristic and is fast and scalable because in the first phase, no alignment is performed with germline database sequences. The algorithms were applied to TR γ HTS data from a patient with acute lymphoblastic leukemia, and also on data simulating hypermutations. Our methods identified the main clone, as well as additional clones that were not identified with standard protocols. Conclusions The proposed algorithms provide new insight into the analysis of high-throughput sequencing data for leukemia, and also to the quantitative assessment of any immunological profile. The methods described here are implemented in a C++ open-source program called Vidjil. Electronic supplementary material The online version of this article (doi:10.1186/1471-2164-15-409) contains supplementary material, which is available to authorized users.

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