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1. AI Competitions and Benchmarks, Practical issues: Proposals, grant money, sponsors, prizes, dissemination, publicity

Author

Richard, Magali, Blum, Yuna, Guinney, Justin, Stolovitzky, Gustavo, and Pavão, Adrien

Subjects
Computer Science - Machine Learning
Abstract

This chapter provides a comprehensive overview of the pragmatic aspects involved in organizing AI competitions. We begin by discussing strategies to incentivize participation, touching upon effective communication techniques, aligning with trending topics in the field, structuring awards, potential recruitment opportunities, and more. We then shift to the essence of community engagement, and into organizational best practices and effective means of disseminating challenge outputs. Lastly, the chapter addresses the logistics, exposing on costs, required manpower, and resource allocation for effectively managing and executing a challenge. By examining these practical problems, readers will gain actionable insights to navigate the multifaceted landscape of AI competition organization, from inception to completion.

Published
2024

3. Pacpaint: a histology-based deep learning model uncovers the extensive intratumor molecular heterogeneity of pancreatic adenocarcinoma

Author

Saillard, Charlie, Delecourt, Flore, Schmauch, Benoit, Moindrot, Olivier, Svrcek, Magali, Bardier-Dupas, Armelle, Emile, Jean Francois, Ayadi, Mira, Rebours, Vinciane, de Mestier, Louis, Hammel, Pascal, Neuzillet, Cindy, Bachet, Jean Baptiste, Iovanna, Juan, Dusetti, Nelson, Blum, Yuna, Richard, Magali, Kermezli, Yasmina, Paradis, Valerie, Zaslavskiy, Mikhail, Courtiol, Pierre, Kamoun, Aurelie, Nicolle, Remy, and Cros, Jerome

Published
2023
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5. Relationships between gut microbiota, plasma metabolites, and metabolic syndrome traits in the METSIM cohort

Author

Org, Elin, Blum, Yuna, Kasela, Silva, Mehrabian, Margarete, Kuusisto, Johanna, Kangas, Antti J, Soininen, Pasi, Wang, Zeneng, Ala-Korpela, Mika, Hazen, Stanley L, Laakso, Markku, and Lusis, Aldons J

Subjects
Medical Biochemistry and Metabolomics, Biological Sciences, Biomedical and Clinical Sciences, Microbiology, Nutrition, Clinical Research, Diabetes, 2.1 Biological and endogenous factors, Aetiology, Metabolic and endocrine, Aged, Amino Acids, Bacteria, Blood Glucose, Body Mass Index, Cohort Studies, Diabetes Mellitus, Type 2, Fatty Acids, Gastrointestinal Microbiome, Glucose Tolerance Test, Humans, Lipids, Male, Metabolic Syndrome, Methylamines, Microbiota, Middle Aged, Phenotype, Host-microbiota interactions, TMAO, Metabolic traits, Serum metabolites, Type 2 diabetes, Environmental Sciences, Information and Computing Sciences, Bioinformatics
Abstract

BackgroundThe gut microbiome is a complex and metabolically active community that directly influences host phenotypes. In this study, we profile gut microbiota using 16S rRNA gene sequencing in 531 well-phenotyped Finnish men from the Metabolic Syndrome In Men (METSIM) study.ResultsWe investigate gut microbiota relationships with a variety of factors that have an impact on the development of metabolic and cardiovascular traits. We identify novel associations between gut microbiota and fasting serum levels of a number of metabolites, including fatty acids, amino acids, lipids, and glucose. In particular, we detect associations with fasting plasma trimethylamine N-oxide (TMAO) levels, a gut microbiota-dependent metabolite associated with coronary artery disease and stroke. We further investigate the gut microbiota composition and microbiota-metabolite relationships in subjects with different body mass index and individuals with normal or altered oral glucose tolerance. Finally, we perform microbiota co-occurrence network analysis, which shows that certain metabolites strongly correlate with microbial community structure and that some of these correlations are specific for the pre-diabetic state.ConclusionsOur study identifies novel relationships between the composition of the gut microbiota and circulating metabolites and provides a resource for future studies to understand host-gut microbiota relationships.

Published
2017

6. Abstract B064: Redefining phenotypic heterogeneity of pancreatic ductal adenocarcinoma: A bottom-up approach

Author

Hilmi, Marc, primary, Delecourt, Flore, additional, Rafenne, Jerôme, additional, Bourega, Taib, additional, Dusetti, Nelson, additional, Iovanna, Juan, additional, Blum, Yuna, additional, Richard, Magali, additional, Neuzillet, Cindy, additional, Couvelard, Anne, additional, De Mestier, Louis, additional, Rebours, Vinciane, additional, Nicolle, Rémy, additional, and Cros, Jérôme, additional

Published
2024
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7. Preclinical evaluation of CDK4 phosphorylation predicts high sensitivity of pleural mesotheliomas to CDK4/6 inhibition.

Author

Paternot, Sabine, Raspé, Eric, Meiller, Clément, Tarabichi, Maxime, Assié, Jean‐Baptiste, Libert, Frederick, Remmelink, Myriam, Bisteau, Xavier, Pauwels, Patrick, Blum, Yuna, Le Stang, Nolwenn, Tabone‐Eglinger, Séverine, Galateau‐Sallé, Françoise, Blanquart, Christophe, Van Meerbeeck, Jan P., Berghmans, Thierry, Jean, Didier, and Roger, Pierre P.

Abstract

Malignant pleural mesothelioma (MPM) is an aggressive cancer with limited therapeutic options. We evaluated the impact of CDK4/6 inhibition by palbociclib in 28 MPM cell lines including 19 patient‐derived ones, using various approaches including RNA‐sequencing. Palbociclib strongly and durably inhibited the proliferation of 23 cell lines, indicating a unique sensitivity of MPM to CDK4/6 inhibition. When observed, insensitivity to palbociclib was mostly explained by the lack of active T172‐phosphorylated CDK4. This was associated with high p16INK4A (CDKN2A) levels that accompany RB1 defects or inactivation, or (unexpectedly) CCNE1 overexpression in the presence of wild‐type RB1. Prolonged palbociclib treatment irreversibly inhibited proliferation despite re‐induction of cell cycle genes upon drug washout. A senescence‐associated secretory phenotype including various potentially immunogenic components was irreversibly induced. Phosphorylated CDK4 was detected in 80% of 47 MPMs indicating their sensitivity to CDK4/6 inhibitors. Its absence in some highly proliferative MPMs was linked to very high p16 (CDKN2A) expression, which was also observed in public datasets in tumours from short‐survival patients. Our study supports the evaluation of CDK4/6 inhibitors for MPM treatment, in monotherapy or combination therapy. [ABSTRACT FROM AUTHOR]

Published
2024
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8. Redefining phenotypic intratumor heterogeneity of pancreatic ductal adenocarcinoma: a bottom-up approach

Author

Hilmi, Marc, primary, Delecourt, Flore, additional, Raffenne, Jérôme, additional, Bourega, Taib, additional, Dusetti, Nelson, additional, Iovanna, Juan, additional, Blum, Yuna, additional, Richard, Magali, additional, Neuzillet, Cindy, additional, Couvelard, Anne, additional, de Mestier, Louis, additional, Rebours, Vinciane, additional, Nicolle, Rémy, additional, and Cros, Jérôme, additional

Published
2023
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10. Multi-site tumor sampling highlights molecular intra-tumor heterogeneity in malignant pleural mesothelioma

Author

Meiller, Clément, Montagne, François, Hirsch, Theo Z., Caruso, Stefano, de Wolf, Julien, Bayard, Quentin, Assié, Jean-Baptiste, Meunier, Léa, Blum, Yuna, Quetel, Lisa, Gibault, Laure, Pintilie, Ecaterina, Badoual, Cécile, Humez, Sarah, Galateau-Sallé, Françoise, Copin, Marie-Christine, Letouzé, Eric, Scherpereel, Arnaud, Zucman-Rossi, Jessica, Le Pimpec-Barthes, Françoise, Jaurand, Marie-Claude, and Jean, Didier

Published
2021
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11. Stratification of Pancreatic Ductal Adenocarcinomas Based on Tumor and Microenvironment Features

Author

Puleo, Francesco, Nicolle, Rémy, Blum, Yuna, Cros, Jérôme, Marisa, Laetitia, Demetter, Pieter, Quertinmont, Eric, Svrcek, Magali, Elarouci, Nabila, Iovanna, Juan, Franchimont, Denis, Verset, Laurine, Galdon, Maria Gomez, Devière, Jacques, de Reyniès, Aurélien, Laurent-Puig, Pierre, Van Laethem, Jean-Luc, Bachet, Jean-Baptiste, and Maréchal, Raphaël

Published
2018
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12. Priming therapy by targeting enhancer-initiated pathways in patient-derived pancreatic cancer cells

Author

Fraunhoffer, Nicolas A., primary, Moreno Vega, Aura I., additional, Abuelafia, Analía Meilerman, additional, Morvan, Marie, additional, Lebarbier, Emilie, additional, Mary-Huard, Tristan, additional, Zimmermann, Michael T., additional, Lomberk, Gwen, additional, Urrutia, Raul, additional, Dusetti, Nelson, additional, Blum, Yuna, additional, Nicolle, Remy, additional, and Iovanna, Juan, additional

Published
2023
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13. Supplementary Table S4 from Genomic Instability and Protumoral Inflammation Are Associated with Primary Resistance to Anti–PD-1 + Antiangiogenesis in Malignant Pleural Mesothelioma

Author

Danlos, François-Xavier, primary, Texier, Matthieu, primary, Job, Bastien, primary, Mouraud, Severine, primary, Cassard, Lydie, primary, Baldini, Capucine, primary, Varga, Andrea, primary, Yurchenko, Andrey A., primary, Rabeau, Audrey, primary, Champiat, Stéphane, primary, Letourneur, Diane, primary, Bredel, Delphine, primary, Susini, Sandrine, primary, Blum, Yuna, primary, Parpaleix, Aurelien, primary, Parlavecchio, Cedric, primary, Tselikas, Lambros, primary, Fahrner, Jean-Eudes, primary, Goubet, Anne-Gaelle, primary, Rouanne, Mathieu, primary, Rafie, Saloomeh, primary, Abbassi, Alae, primary, Kasraoui, Ines, primary, Breckler, Marie, primary, Farhane, Siham, primary, Ammari, Samy, primary, Laghouati, Salim, primary, Gazzah, Anas, primary, Lacroix, Ludovic, primary, Besse, Benjamin, primary, Droin, Nathalie, primary, Deloger, Marc, primary, Cotteret, Sophie, primary, Adam, Julien, primary, Zitvogel, Laurence, primary, Nikolaev, Sergey I., primary, Chaput, Nathalie, primary, Massard, Christophe, primary, Soria, Jean-Charles, primary, Gomez-Roca, Carlos, primary, Zalcman, Gerard, primary, Planchard, David, primary, and Marabelle, Aurelien, primary

Published
2023
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14. Supplementary Figure S5 from Genomic Instability and Protumoral Inflammation Are Associated with Primary Resistance to Anti–PD-1 + Antiangiogenesis in Malignant Pleural Mesothelioma

Author

Danlos, François-Xavier, primary, Texier, Matthieu, primary, Job, Bastien, primary, Mouraud, Severine, primary, Cassard, Lydie, primary, Baldini, Capucine, primary, Varga, Andrea, primary, Yurchenko, Andrey A., primary, Rabeau, Audrey, primary, Champiat, Stéphane, primary, Letourneur, Diane, primary, Bredel, Delphine, primary, Susini, Sandrine, primary, Blum, Yuna, primary, Parpaleix, Aurelien, primary, Parlavecchio, Cedric, primary, Tselikas, Lambros, primary, Fahrner, Jean-Eudes, primary, Goubet, Anne-Gaelle, primary, Rouanne, Mathieu, primary, Rafie, Saloomeh, primary, Abbassi, Alae, primary, Kasraoui, Ines, primary, Breckler, Marie, primary, Farhane, Siham, primary, Ammari, Samy, primary, Laghouati, Salim, primary, Gazzah, Anas, primary, Lacroix, Ludovic, primary, Besse, Benjamin, primary, Droin, Nathalie, primary, Deloger, Marc, primary, Cotteret, Sophie, primary, Adam, Julien, primary, Zitvogel, Laurence, primary, Nikolaev, Sergey I., primary, Chaput, Nathalie, primary, Massard, Christophe, primary, Soria, Jean-Charles, primary, Gomez-Roca, Carlos, primary, Zalcman, Gerard, primary, Planchard, David, primary, and Marabelle, Aurelien, primary

Published
2023
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15. Data from Genomic Instability and Protumoral Inflammation Are Associated with Primary Resistance to Anti–PD-1 + Antiangiogenesis in Malignant Pleural Mesothelioma

Author

Danlos, François-Xavier, primary, Texier, Matthieu, primary, Job, Bastien, primary, Mouraud, Severine, primary, Cassard, Lydie, primary, Baldini, Capucine, primary, Varga, Andrea, primary, Yurchenko, Andrey A., primary, Rabeau, Audrey, primary, Champiat, Stéphane, primary, Letourneur, Diane, primary, Bredel, Delphine, primary, Susini, Sandrine, primary, Blum, Yuna, primary, Parpaleix, Aurelien, primary, Parlavecchio, Cedric, primary, Tselikas, Lambros, primary, Fahrner, Jean-Eudes, primary, Goubet, Anne-Gaelle, primary, Rouanne, Mathieu, primary, Rafie, Saloomeh, primary, Abbassi, Alae, primary, Kasraoui, Ines, primary, Breckler, Marie, primary, Farhane, Siham, primary, Ammari, Samy, primary, Laghouati, Salim, primary, Gazzah, Anas, primary, Lacroix, Ludovic, primary, Besse, Benjamin, primary, Droin, Nathalie, primary, Deloger, Marc, primary, Cotteret, Sophie, primary, Adam, Julien, primary, Zitvogel, Laurence, primary, Nikolaev, Sergey I., primary, Chaput, Nathalie, primary, Massard, Christophe, primary, Soria, Jean-Charles, primary, Gomez-Roca, Carlos, primary, Zalcman, Gerard, primary, Planchard, David, primary, and Marabelle, Aurelien, primary

Published
2023
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17. Data from Combined MEK and PI3K/p110β Inhibition as a Novel Targeted Therapy for Malignant Mesothelioma Displaying Sarcomatoid Features

Author

Marqués, Miriam, primary, Tranchant, Robin, primary, Risa-Ebrí, Blanca, primary, Suárez-Solís, María L., primary, Fernández, Luis C., primary, Carrillo-de-Santa-Pau, Enrique, primary, del Pozo, Natalia, primary, Martínez de Villarreal, Jaime, primary, Meiller, Clément, primary, Allory, Yves, primary, Blum, Yuna, primary, Pirker, Christine, primary, Hegedus, Balazs, primary, Barry, Simon T., primary, Carnero, Amancio, primary, Berger, Walter, primary, Jean, Didier, primary, and Real, Francisco X., primary

Published
2023
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18. Data from Intratumor CMS Heterogeneity Impacts Patient Prognosis in Localized Colon Cancer

Author

Marisa, Laetitia, primary, Blum, Yuna, primary, Taieb, Julien, primary, Ayadi, Mira, primary, Pilati, Camilla, primary, Le Malicot, Karine, primary, Lepage, Côme, primary, Salazar, Ramon, primary, Aust, Daniela, primary, Duval, Alex, primary, Blons, Hélène, primary, Taly, Valérie, primary, Gentien, David, primary, Rapinat, Audrey, primary, Selves, Janick, primary, Mouillet-Richard, Sophie, primary, Boige, Valérie, primary, Emile, Jean-François, primary, de Reyniès, Aurélien, primary, and Laurent-Puig, Pierre, primary

Published
2023
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19. Supplementary Data from Combined MEK and PI3K/p110β Inhibition as a Novel Targeted Therapy for Malignant Mesothelioma Displaying Sarcomatoid Features

Author

Marqués, Miriam, primary, Tranchant, Robin, primary, Risa-Ebrí, Blanca, primary, Suárez-Solís, María L., primary, Fernández, Luis C., primary, Carrillo-de-Santa-Pau, Enrique, primary, del Pozo, Natalia, primary, Martínez de Villarreal, Jaime, primary, Meiller, Clément, primary, Allory, Yves, primary, Blum, Yuna, primary, Pirker, Christine, primary, Hegedus, Balazs, primary, Barry, Simon T., primary, Carnero, Amancio, primary, Berger, Walter, primary, Jean, Didier, primary, and Real, Francisco X., primary

Published
2023
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20. Supplementary Data from Intratumor CMS Heterogeneity Impacts Patient Prognosis in Localized Colon Cancer

Author

Marisa, Laetitia, primary, Blum, Yuna, primary, Taieb, Julien, primary, Ayadi, Mira, primary, Pilati, Camilla, primary, Le Malicot, Karine, primary, Lepage, Côme, primary, Salazar, Ramon, primary, Aust, Daniela, primary, Duval, Alex, primary, Blons, Hélène, primary, Taly, Valérie, primary, Gentien, David, primary, Rapinat, Audrey, primary, Selves, Janick, primary, Mouillet-Richard, Sophie, primary, Boige, Valérie, primary, Emile, Jean-François, primary, de Reyniès, Aurélien, primary, and Laurent-Puig, Pierre, primary

Published
2023
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21. Genomic Instability and Protumoral Inflammation Are Associated with Primary Resistance to Anti–PD-1 + Antiangiogenesis in Malignant Pleural Mesothelioma

Author

Danlos, François-Xavier, primary, Texier, Matthieu, additional, Job, Bastien, additional, Mouraud, Severine, additional, Cassard, Lydie, additional, Baldini, Capucine, additional, Varga, Andrea, additional, Yurchenko, Andrey A., additional, Rabeau, Audrey, additional, Champiat, Stéphane, additional, Letourneur, Diane, additional, Bredel, Delphine, additional, Susini, Sandrine, additional, Blum, Yuna, additional, Parpaleix, Aurelien, additional, Parlavecchio, Cedric, additional, Tselikas, Lambros, additional, Fahrner, Jean-Eudes, additional, Goubet, Anne-Gaelle, additional, Rouanne, Mathieu, additional, Rafie, Saloomeh, additional, Abbassi, Alae, additional, Kasraoui, Ines, additional, Breckler, Marie, additional, Farhane, Siham, additional, Ammari, Samy, additional, Laghouati, Salim, additional, Gazzah, Anas, additional, Lacroix, Ludovic, additional, Besse, Benjamin, additional, Droin, Nathalie, additional, Deloger, Marc, additional, Cotteret, Sophie, additional, Adam, Julien, additional, Zitvogel, Laurence, additional, Nikolaev, Sergey I., additional, Chaput, Nathalie, additional, Massard, Christophe, additional, Soria, Jean-Charles, additional, Gomez-Roca, Carlos, additional, Zalcman, Gerard, additional, Planchard, David, additional, and Marabelle, Aurelien, additional

Published
2023
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22. Ephrin-B1 regulates the adult diastolic function through a late postnatal maturation of cardiomyocyte surface crests

Author

Karsenty, Clement, primary, Guilbeau-Frugier, Celine, additional, Genet, Gaël, additional, Seguelas, Marie-Helene, additional, Alzieu, Philippe, additional, Cazorla, Olivier, additional, Montagner, Alexandra, additional, Blum, Yuna, additional, Dubroca, Caroline, additional, Maupoint, Julile, additional, Tramunt, Blandine, additional, Cauquil, Marie, additional, Sulpice, Thierry, additional, Richard, Sylvain, additional, Arcucci, Silvia, additional, Flores-Flores, Remy, additional, Pataluch, Nicolas, additional, Montoriol, Romain, additional, Sicard, Pierre, additional, Deney, Antoine, additional, Couffinhal, Thierry, additional, Senard, Jean-Michel, additional, and Galés, Celine, additional

Published
2023
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23. Dissecting heterogeneity in malignant pleural mesothelioma through histo-molecular gradients for clinical applications

Author

Blum, Yuna, Meiller, Clément, Quetel, Lisa, Elarouci, Nabila, Ayadi, Mira, Tashtanbaeva, Danisa, Armenoult, Lucile, Montagne, François, Tranchant, Robin, Renier, Annie, de Koning, Leanne, Copin, Marie-Christine, Hofman, Paul, Hofman, Véronique, Porte, Henri, Le Pimpec-Barthes, Françoise, Zucman-Rossi, Jessica, Jaurand, Marie-Claude, de Reyniès, Aurélien, and Jean, Didier

Published
2019
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24. Author response: Ephrin-B1 regulates the adult diastolic function through a late postnatal maturation of cardiomyocyte surface crests

Author

Karsenty, Clement, primary, Guilbeau-Frugier, Celine, additional, Genet, Gaël, additional, Seguelas, Marie-Helene, additional, Alzieu, Philippe, additional, Cazorla, Olivier, additional, Montagner, Alexandra, additional, Blum, Yuna, additional, Dubroca, Caroline, additional, Maupoint, Julile, additional, Tramunt, Blandine, additional, Cauquil, Marie, additional, Sulpice, Thierry, additional, Richard, Sylvain, additional, Arcucci, Silvia, additional, Flores-Flores, Remy, additional, Pataluch, Nicolas, additional, Montoriol, Romain, additional, Sicard, Pierre, additional, Deney, Antoine, additional, Couffinhal, Thierry, additional, Senard, Jean-Michel, additional, and Galés, Celine, additional

Published
2022
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25. Preclinical evaluation of CDK4 phosphorylation predicts high sensitivity of pleural mesotheliomas to CDK4 /6 inhibition

Author

Paternot, Sabine, primary, Raspé, Eric, additional, Meiller, Clément, additional, Tarabichi, Maxime, additional, Assié, Jean‐Baptiste, additional, Libert, Frederick, additional, Remmelink, Myriam, additional, Bisteau, Xavier, additional, Pauwels, Patrick, additional, Blum, Yuna, additional, Le Stang, Nolwenn, additional, Tabone‐Eglinger, Séverine, additional, Galateau‐Sallé, Françoise, additional, Blanquart, Christophe, additional, Van Meerbeeck, Jan P., additional, Berghmans, Thierry, additional, Jean, Didier, additional, and Roger, Pierre P., additional

Published
2022
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26. Preclinical evaluation of CDK4 phosphorylation predicts high sensitivity of malignant pleural mesotheliomas to CDK4/6 inhibition

Author

Paternot, Sabine, primary, Raspe, Eric, additional, Meiller, Clement, additional, Tarabichi, Maxime, additional, Assie, Jean-Baptiste, additional, Libert, Frederick, additional, Remmelink, Myriam, additional, Bisteau, Xavier, additional, Pauwels, Patrick, additional, Blum, Yuna, additional, Le Stang, Nolwenn, additional, Tabone-Eglinger, Severine, additional, Galateau-Salle, Francoise, additional, Blanquart, Christophe, additional, Van Meerbeeck, Jan P., additional, Berghmans, Thierry, additional, Jean, Didier, additional, and Roger, Pierre P., additional

Published
2022
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27. Crest maturation at the cardiomyocyte surface contributes to a new late postnatal development stage that controls the diastolic function of the adult heart

Author

Karsenty, Clément, primary, Guilbeau-Frugier, Céline, additional, Genet, Gaël, additional, Seguelas, Marie-Hélène, additional, Alzieu, Philippe, additional, Cazorla, Olivier, additional, Montagner, Alexandra, additional, Blum, Yuna, additional, Dubroca, Caroline, additional, Maupoint, Julie, additional, Tramunt, Blandine, additional, Cauquil, Marie, additional, Sulpice, Thierry, additional, Richard, Sylvain, additional, Arcucci, Silvia, additional, Flores-Flores, Remy, additional, Pataluch, Nicolas, additional, Montoriol, Romain, additional, Sicard, Pierre, additional, Deney, Antoine, additional, Couffinhal, Thierry, additional, Sénard, Jean-Michel, additional, and Galés, Céline, additional

Published
2022
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28. PACpAInt: a deep learning approach to identify molecular subtypes of pancreatic adenocarcinoma on histology slides

Author

Saillard, Charlie, primary, Delecourt, Flore, additional, Schmauch, Benoit, additional, Moindrot, Olivier, additional, Svrcek, Magali, additional, Bardier-Dupas, Armelle, additional, Emile, Jean-Francois, additional, Ayadi, Mira, additional, Rebours, Vinciane, additional, de Mestier, Louis, additional, Hammel, Pascal, additional, Neuzillet, Cindy, additional, Bachet, Jean-Baptiste, additional, Iovanna, Juan, additional, Dusetti, Nelson, additional, Blum, Yuna, additional, Richard, Magalie, additional, Kermezli, Yasmina, additional, Paradis, Valerie, additional, Zaslavskiy, Mikhail, additional, Courtiol, Pierre, additional, Kamoun, Aurelie, additional, Nicolle, Remy, additional, and Cros, Jerome, additional

Published
2022
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29. Abstract 3128: Spatial intra-tumor molecular heterogeneity in malignant pleural mesothelioma

Author

Meiller, Clément, primary, Montagne, François, additional, Hirsch, Théo Z., additional, Caruso, Stefano, additional, de Wolf, Julien, additional, Bayard, Quentin, additional, Assié, Jean-Baptiste, additional, Meunier, Léa, additional, Blum, Yuna, additional, Quetel, Lisa, additional, Gibault, Laure, additional, Pintilie, Ecaterina, additional, Badoual, Cécile, additional, Copin, Marie-Christine, additional, Letouzé, Eric, additional, Scherpereel, Arnaud, additional, Zucman-Rossi, Jessica, additional, Pimpec-Barthes, Françoise Le, additional, Jaurand, Marie-Claude, additional, and Jean, Didier, additional

Published
2021
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30. Additional file 1 of DECONbench: a benchmarking platform dedicated to deconvolution methods for tumor heterogeneity quantification

Author

Decamps, Clémentine, Arnaud, Alexis, Petitprez, Florent, Ayadi, Mira, Baurès, Aurélia, Armenoult, Lucile, Escalera, Sergio, Guyon, Isabelle, Nicolle, Rémy, Tomasini, Richard, de Reyniès, Aurélien, Cros, Jérôme, Blum, Yuna, and Richard, Magali

Subjects
FOS: Computer and information sciences, FOS: Biological sciences, Genetics, FOS: Mathematics, 19999 Mathematical Sciences not elsewhere classified, 80699 Information Systems not elsewhere classified, 69999 Biological Sciences not elsewhere classified, Cancer
Abstract

Additional file 1: Figure S1: DECONbench benchmark of OLS and RLR methods: an example of graphical outputs of new contributions to the benchmark. Source code.

Published
2021
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31. Additional file 2 of Multi-site tumor sampling highlights molecular intra-tumor heterogeneity in malignant pleural mesothelioma

Author

Meiller, Clément, Montagne, François, Hirsch, Theo Z., Caruso, Stefano, de Wolf, Julien, Bayard, Quentin, Assié, Jean-Baptiste, Meunier, Léa, Blum, Yuna, Quetel, Lisa, Gibault, Laure, Pintilie, Ecaterina, Badoual, Cécile, Humez, Sarah, Galateau-Sallé, Françoise, Copin, Marie-Christine, Letouzé, Eric, Scherpereel, Arnaud, Zucman-Rossi, Jessica, Le Pimpec-Barthes, Françoise, Jaurand, Marie-Claude, and Jean, Didier

Abstract

Additional file 2: Figure S1. Positron emission tomography (PET) scans of the two patients with biopsies performed on highest metabolite sites. Figure S2. Frequencies of BAP1 and NF2 variants in the fresh tumor sample used to generate the MPM_83 primary cell line. Figure S3. Cancer cell fraction in paired MPM samples. Figure S4. Pangenomic copy number variation profile determined by DNAcopy. Figure S5. Pangenomic copy number variation profile determined by FACET. Figure S6. Fusion transcripts identified by RNA-seq. Figure S7. Unsupervised clustering of MPM tumor samples based on gene expression profiles. Figure S8. Differentially expressed genes between paired tumor samples. Figure S9. Single sample Gene Set Enrichment Analysis (ssGSEA) for pathways related to cell adhesion and extracellular matrix. Figure S10. Epigenetic intra-tumor heterogeneity. Figure S11. Differential infiltration of stromal and immune cell populations. Figure S12. Distribution of immune and stromal populations among paired tumor samples. Figure S13. Single sample Gene Set Enrichment Analysis (ssGSEA) for pathways related to immune cell infiltration. Figure S14. Immunohistochemical staining of tumor-infiltrating T and B cells in patients with paired tumor samples switching from a cold to a hot immune profile.

Published
2021
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32. Intratumor CMS Heterogeneity Impacts Patient Prognosis in Localized Colon Cancer

Author

Marisa, Laetitia, primary, Blum, Yuna, additional, Taieb, Julien, additional, Ayadi, Mira, additional, Pilati, Camilla, additional, Le Malicot, Karine, additional, Lepage, Côme, additional, Salazar, Ramon, additional, Aust, Daniela, additional, Duval, Alex, additional, Blons, Hélène, additional, Taly, Valérie, additional, Gentien, David, additional, Rapinat, Audrey, additional, Selves, Janick, additional, Mouillet-Richard, Sophie, additional, Boige, Valérie, additional, Emile, Jean-François, additional, de Reyniès, Aurélien, additional, and Laurent-Puig, Pierre, additional

Published
2021
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33. Integrative study of diet-induced mouse models of NAFLD identifies PPARα as a sexually dimorphic drug target

Author

Smati, Sarra, primary, Polizzi, Arnaud, additional, Fougerat, Anne, additional, Ellero-Simatos, Sandrine, additional, Blum, Yuna, additional, Lippi, Yannick, additional, Régnier, Marion, additional, Laroyenne, Alexia, additional, Huillet, Marine, additional, Arif, Muhammad, additional, Zhang, Cheng, additional, Lasserre, Frederic, additional, Marrot, Alain, additional, Al Saati, Talal, additional, Wan, JingHong, additional, Sommer, Caroline, additional, Naylies, Claire, additional, Batut, Aurelie, additional, Lukowicz, Celine, additional, Fougeray, Tiffany, additional, Tramunt, Blandine, additional, Dubot, Patricia, additional, Smith, Lorraine, additional, Bertrand-Michel, Justine, additional, Hennuyer, Nathalie, additional, Pradere, Jean-Philippe, additional, Staels, Bart, additional, Burcelin, Remy, additional, Lenfant, Françoise, additional, Arnal, Jean-François, additional, Levade, Thierry, additional, Gamet-Payrastre, Laurence, additional, Lagarrigue, Sandrine, additional, Loiseau, Nicolas, additional, Lotersztajn, Sophie, additional, Postic, Catherine, additional, Wahli, Walter, additional, Bureau, Christophe, additional, Guillaume, Maeva, additional, Mardinoglu, Adil, additional, Montagner, Alexandra, additional, Gourdy, Pierre, additional, and Guillou, Hervé, additional

Published
2021
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34. Integrative study of diet-induced mouse models of NAFLD identifies PPARα as a sexually dimorphic drug target.

Author

Smati, Sarra, Polizzi, Arnaud, Fougerat, Anne, Ellero-Simatos, Sandrine, Blum, Yuna, Lippi, Yannick, Régnier, Marion, Laroyenne, Alexia, Huillet, Marine, Arif, Muhammad, Cheng Zhang, Lasserre, Frederic, Marrot, Alain, Al Saati, Talal, JingHong Wan, Sommer, Caroline, Naylies, Claire, Batut, Aurelie, Lukowicz, Celine, and Fougeray, Tiffany

Subjects
FATTY liver, CHOLESTEROL content of food, NON-alcoholic fatty liver disease, ELLAGIC acid, DRUG target, SEXUAL dimorphism, LABORATORY mice, NF-kappa B
Published
2022
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35. Pancreatic Ductal Adenocarcinoma Arising in Young and Old Patients Displays Similar Molecular Features

Author

Raffenne, Jérôme, primary, Martin, Fernando A., additional, Nicolle, Rémy, additional, Konta, Marina, additional, Blum, Yuna, additional, Torrisani, Jérôme, additional, Puleo, Francesco, additional, Bachet, Jean Baptiste, additional, Svrcek, Magali, additional, Bardier-Dupas, Armel, additional, Emile, Jean Francois, additional, Demetter, Peter, additional, Radman, Miroslav, additional, Van Laethem, Jean Luc, additional, Hammel, Pascal, additional, Rebours, Vinciane, additional, Paradis, Valérie, additional, Couvelard, Anne, additional, and Cros, Jérôme, additional

Published
2021
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36. A transcriptomic signature to predict adjuvant gemcitabine sensitivity in pancreatic adenocarcinoma

Author

Nicolle, R, Gayet, O, Duconseil, P, Vanbrugghe, C, Roques, Julie, Bigonnet, M, Blum, Yuna, Elarouci, Nabila, Armenoult, L, Ayadi, M, de Reyniès, Aurélien, Puleo, Francesco, Augustin, J, Emile, J F, Svrcek, Magali, Arsenijevic, Tatjana, Hammel, P, Giovannini, M, Grandval, P, Dahan, Laeticia, Moutardier, V, Gilabert, M, Van Laethem, Jean-Luc, Bachet, J B, Cros, Jérôme, Iovanna, J, and Dusetti, N J

Subjects
Chemosensitivity Prediction, Precision medicine, Sciences bio-médicales et agricoles, Adenocarcinoma, Deoxycytidine, Gemcitabine, digestive system diseases, Pancreatic Neoplasms, Pancreatic Cancer, Chemotherapy, Adjuvant, Transcriptomic Signature, Humans, Transcriptome, Carcinoma, Pancreatic Ductal, Retrospective Studies
Abstract

Chemotherapy is the only systemic treatment approved for pancreatic ductal adenocarcinoma (PDAC), with a selection of regimens based on patients' performance status and expected efficacy. The establishment of a potent stratification associated with chemotherapeutic efficacy could potentially improve prognosis by tailoring treatments., info:eu-repo/semantics/published

Published
2020

37. Establishment of a pancreatic adenocarcinoma molecular gradient (PAMG) that predicts the clinical outcome of pancreatic cancer

Author

Nicolle, Rémy, Blum, Yuna, Duconseil, Pauline, Vanbrugghe, Charles, Brandone, Nicolas, Poizat, Flora, Roques, Julie, Bigonnet, Martin, Gayet, Odile, Rubis, Marion, Dou, Samir, Elarouci, Nabila, Armenoult, Lucile, Ayadi, Mira, de Reyniès, Aurélien, Giovannini, Marc, Grandval, Philippe, Garcia, Stephane, Canivet, Cindy, Cros, Jérôme, Bournet, Barbara, Buscail, Louis, Moutardier, Vincent, Gilabert, Marine, Iovanna, Juan, and Dusetti, Nelson

Subjects
Oncology, Male, Research paper, endocrine system diseases, Personalized treatment, Leucovorin, lcsh:Medicine, Tumor response, Mice, Antineoplastic Combined Chemotherapy Protocols, Neoplasm Metastasis, Precision Medicine, lcsh:R5-920, Clinical Trials as Topic, medicine.diagnostic_test, Middle Aged, Prognosis, Predictive value, Well differentiated, Neoplasm Proteins, Gene Expression Regulation, Neoplastic, Oxaliplatin, Adenocarcinoma, Heterografts, Female, Translational medicine, Fluorouracil, lcsh:Medicine (General), Adult, medicine.medical_specialty, Adolescent, Transcriptomic signature, Irinotecan, Prognostic, Disease-Free Survival, Young Adult, Chemosensitivity prediction, Internal medicine, Pancreatic cancer, Cell Line, Tumor, Biopsy, medicine, Biomarkers, Tumor, Animals, Humans, Endoscopic Ultrasound-Guided Fine Needle Aspiration, Aged, business.industry, lcsh:R, Histology, medicine.disease, Pancreatic Neoplasms, Drug Resistance, Neoplasm, business, Transcriptome
Abstract

BACKGROUNDA significant gap in pancreatic ductal adenocarcinoma (PDAC) patient’s care is the lack of molecular parameters characterizing tumors and allowing a personalized treatment. The goal of this study was to examine whole PDAC transcriptomic profiles to define a signature that would predict aggressiveness and treatment responsiveness better than done until now.METHODS AND PATIENTSTumors were obtained from 76 consecutive resectable (n=40) or unresectable (n=36) tumors. PDAC were transplanted in mice to produce patient-drived xenografts (PDX). PDX were classified according to their histology into five groups, from highly undifferentiated to well differentiated. This classification resulted strongly associated with tumors aggressiveness. A PDAC molecular gradient (PAMG) was constructed from PDX transcriptomes recapitulating the five histological groups along a continuous gradient. The prognostic and predictive value for PMAG was evaluated in: i/ two independent series (n=598) of resected tumors; ii/ 60 advanced tumors obtained by diagnostic EUS-guided biopsy needle flushing and iii/ on 28 biopsies from mFOLFIRINOX treated metastatic tumors.RESULTSA unique transcriptomic signature (PAGM) was generated with significant and independent prognostic value. PAMG significantly improves the characterization of PDAC heterogeneity compared to non-overlapping classifications as validated in 4 independent series of tumors (e.g. 308 consecutive resected PDAC, HR=0.321 95% CI [0.207;0.5] and 60 locally-advanced or metastatic PDAC, HR=0.308 95% CI [0.113;0.836]). The PAMG signature is also associated with progression under mFOLFIRINOX treatment (Pearson correlation to tumor response: -0.67, p-value < 0.001).CONCLUSIONWe identified a transcriptomic signature (PAMG) that, unlike all other stratification schemas already proposed, classifies PDAC along a continuous gradient. It can be performed on formalin-fixed paraffin-embedded samples and EUS-guided biopsies showing a strong prognostic value and predicting mFOLFIRINOX responsiveness. We think that PAMG could unify all PDAC preexisting classifications inducing a shift in the actual paradigm of binary classifications towards a better characterization in a gradient.Trial RegistrationThe PaCaOmics study is registered atwww.clinicaltrials.govwith registration numberNCT01692873. The validation BACAP study is registered atwww.clinicaltrials.govwith registration numberNCT02818829.

Published
2020

38. Genetic alterations of malignant pleural mesothelioma: association to tumor heterogeneity and overall survival Author names

Author

Quetel, Lisa, Meiller, Clément, Assié, Jean-Baptiste, Blum, Yuna, Imbeaud, Sandrine, Montagne, François, Tranchant, Robin, de Wolf, Julien, Caruso, Stefano, Copin, Marie-Christine, Hofman, Véronique, Gibault, Laure, Badoual, Cecile, Pintilie, Ecaterina, Hofman, Paul, Monnet, Isabelle, Scherpereel, Arnaud, Le Pimpec-Barthes, Françoise, Zucman-Rossi, Jessica, Jaurand, Marie-Claude, Jean, Didier, Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), (le programme) Cartes d'identité des tumeurs (CIT), Ligue Nationales Contre le Cancer (LNCC), Genexpress, Génomique Fonctionnelle et Biologie Systémique pour la Santé, Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Institut de Pathologie [CHU Lille], Pôle de Biologie Pathologie Génétique [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Lille, Laboratoire de Pathologie Clinique et Expérimentale. Hôpital Pasteur [Nice], Hôpital Pasteur [Nice] (CHU), FHU OncoAge - Pathologies liées à l’âge [CHU Nice] (OncoAge), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Institut de Pharmacologie Moléculaire et Cellulaire [UNIV Côte d'Azur] (UPMC), Service d'Anatomo-cytopathologie [Hôpital Européen Georges Pompidou - APHP], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de Chirurgie Thoracique [CHRU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Pneumologie et de Pathologie Professionnelle [CHI Créteil], CHI Créteil, Réseau National Expert pour le Mésothéliome Pleural Malin [Lille] (MESOCLIN), Pneumologie et Oncologie Thoracique [CHRU de Lille], PRES Université Lille Nord de France-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Hôpital Albert Calmette-Faculté de Médecine Henri Warembourg, Service de Chirurgie Thoracique (Hôpital Européen Georges Pompidou [APHP] HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), This work was supported by Inserm, the Ligue Contre le Cancer (Ile de France committee and national program Cartes d’Identité des Tumeurs (CIT)), the Fondation ARC pour la recherche sur le cancer, Hadassah France, and the Chancellerie des Universités de Paris (Legs POIX). LQ, JBA, FM and JdW were supported by grants from Cancéropôle Région Île-de France, from Fondation pour la Recherche Médicale (FRM), from the Institut thématique multi-organismes (ITMO) Cancer (Plan Cancer 2014-2019) and from the Fondation ARC, respectively. JdW and FM were also supported by grant of the Société Française de Chirurgie Thoracique et Cardio-Vasculaire (SFCTCV). The Inserm research unit is supported by the Labex OncoImmunology (investissement d’avenir), Coup d’Elan de la Fondation Bettencourt-Shueller, the SIRIC CARPEM, the Institut thématique multi-organismes (ITMO) Cancer (Plan Cancer 2014-2019) and Cancéropôle Île-de-France., École Pratique des Hautes Études (EPHE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Pharmacologie Moléculaire et Cellulaire [UNIV Côte d'Azur] (UPMC)-Université Côte d'Azur (UCA), PRES Université Lille Nord de France-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Faculté de Médecine Henri Warembourg - Université de Lille-Hôpital Albert Calmette, and Jean, Didier

Subjects
tumor molecular classification, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Thoracic cancer, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], tumor heterogeneity, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], prognosis, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, gene mutations
Abstract

International audience; Development of precision medicine for malignant pleural mesothelioma (MPM) requires a deep knowledge of tumor heterogeneity. Histologic and molecular classifications and histo-molecular gradients have been proposed to describe heterogeneity, but a deeper understanding of gene mutations in the context of MPM heterogeneity is required and the associations between mutations and clinical data need to be refined. We characterized genetic alterations on one of the largest MPM series (266 tumor samples), well-annotated with histologic, molecular and clinical data of patients. Targeted next generation sequencing was performed focusing on the major MPM mutated genes and the TERT promoter. Molecular heterogeneity was characterized using predictors allowing classification of each tumor into the previously described molecular subtypes and the determination of the proportion of epithelioïd-like and sarcomatoïd-like components (E/S.scores). The mutation frequencies are consistent with literature data, but this study emphasized that TERT promoter, not considered by previous large sequencing studies, was the third locus most affected by mutations in MPM. Mutations in TERT promoter, NF2 and LATS2 were more frequent in non-epithelioid MPM and positively associated to the S.score. BAP1, NF2, TERT promoter, TP53 and SETD2 mutations were enriched in some molecular subtypes. NF2 mutation rate was higher in asbestos unexposed patient. TERT promoter, NF2 and TP53 mutations were associated with a poorer overall survival. Our findings lead to a better characterization of MPM heterogeneity by identifying new significant associations between mutational status and histologic and molecular heterogeneity. Strikingly, we highlight the strong association between new mutations and overall survival.

Published
2020

40. Genetic alterations of malignant pleural mesothelioma: association with tumor heterogeneity and overall survival

Author

Quetel, Lisa, primary, Meiller, Clément, additional, Assié, Jean‐Baptiste, additional, Blum, Yuna, additional, Imbeaud, Sandrine, additional, Montagne, François, additional, Tranchant, Robin, additional, de Wolf, Julien, additional, Caruso, Stefano, additional, Copin, Marie‐Christine, additional, Hofman, Véronique, additional, Gibault, Laure, additional, Badoual, Cécile, additional, Pintilie, Ecaterina, additional, Hofman, Paul, additional, Monnet, Isabelle, additional, Scherpereel, Arnaud, additional, Le Pimpec‐Barthes, Françoise, additional, Zucman‐Rossi, Jessica, additional, Jaurand, Marie‐Claude, additional, and Jean, Didier, additional

Published
2020
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41. Combined MEK and PI3K/p110β Inhibition as a Novel Targeted Therapy for Malignant Mesothelioma Displaying Sarcomatoid Features

Author

Marqués, Miriam, primary, Tranchant, Robin, additional, Risa-Ebrí, Blanca, additional, Suárez-Solís, María L., additional, Fernández, Luis C., additional, Carrillo-de-Santa-Pau, Enrique, additional, del Pozo, Natalia, additional, Martínez de Villarreal, Jaime, additional, Meiller, Clément, additional, Allory, Yves, additional, Blum, Yuna, additional, Pirker, Christine, additional, Hegedus, Balazs, additional, Barry, Simon T., additional, Carnero, Amancio, additional, Berger, Walter, additional, Jean, Didier, additional, and Real, Francisco X., additional

Published
2020
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42. PDAC Arising in Young and Old Patients Display Similar Molecular Features

Author

Raffenne, Jerome, primary, Martin, Fernando Ariel, additional, Nicolle, Rémy, additional, Konta, Marina, additional, Blum, Yuna, additional, Torrisani, Jerome, additional, Puleo, Francesco, additional, Bachet, Jean Baptiste, additional, Svrcek, Magali, additional, Bardier-Dupas, Armel, additional, Emile, Jean-François, additional, Demetter, Peter, additional, Radman, Miroslav, additional, Van Laethem, Jean Luc, additional, Hammel, Pascal, additional, Rebours, Vinciane, additional, Paradis, Valérie, additional, Couvelard, Anne, additional, and Cros, Jerome, additional

Published
2020
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43. Chicken adaptive response to low energy diet: main role of the hypothalamic lipid metabolism revealed by a phenotypic and multi-tissue transcriptomic approach

Author

Jehl, Frédéric, primary, Désert, Colette, additional, Klopp, Christophe, additional, Brenet, Marine, additional, Rau, Andrea, additional, Leroux, Sophie, additional, Boutin, Morgane, additional, Lagoutte, Laetitia, additional, Muret, Kévin, additional, Blum, Yuna, additional, Esqu, Diane, additional, Gourichon, David, additional, Burlot, Thierry, additional, Collin, Anne, additional, Pitel, Frédérique, additional, Benani, Alexandre, additional, Zerjal, Tatiana, additional, and Lagarrigue, Sandrine, additional

Published
2019
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44. Multi-omic approaches unveil new therapeutic targets for the treatment of pancreatic cancer

Author

Nicolle, Remy, Blum, Yuna, Marisa, Laetitia, Dusetti, Nelson, Iovanna, Juan, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-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)-Institut Paoli-Calmettes, and Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU)

Subjects
[SDV]Life Sciences [q-bio]
Published
2018

47. Complex trait subtypes identification using transcriptome profiling reveals an interaction between two QTL affecting adiposity in chicken

Author

Blum Yuna, Le Mignon Guillaume, Causeur David, Filangi Olivier, Désert Colette, Demeure Olivier, Le Roy Pascale, and Lagarrigue Sandrine

Subjects
Biotechnology, TP248.13-248.65, Genetics, QH426-470
Abstract

Abstract Background Integrative genomics approaches that combine genotyping and transcriptome profiling in segregating populations have been developed to dissect complex traits. The most common approach is to identify genes whose eQTL colocalize with QTL of interest, providing new functional hypothesis about the causative mutation. Another approach includes defining subtypes for a complex trait using transcriptome profiles and then performing QTL mapping using some of these subtypes. This approach can refine some QTL and reveal new ones. In this paper we introduce Factor Analysis for Multiple Testing (FAMT) to define subtypes more accurately and reveal interaction between QTL affecting the same trait. The data used concern hepatic transcriptome profiles for 45 half sib male chicken of a sire known to be heterozygous for a QTL affecting abdominal fatness (AF) on chromosome 5 distal region around 168 cM. Results Using this methodology which accounts for hidden dependence structure among phenotypes, we identified 688 genes that are significantly correlated to the AF trait and we distinguished 5 subtypes for AF trait, which are not observed with gene lists obtained by classical approaches. After exclusion of one of the two lean bird subtypes, linkage analysis revealed a previously undetected QTL on chromosome 5 around 100 cM. Interestingly, the animals of this subtype presented the same q paternal haplotype at the 168 cM QTL. This result strongly suggests that the two QTL are in interaction. In other words, the "q configuration" at the 168 cM QTL could hide the QTL existence in the proximal region at 100 cM. We further show that the proximal QTL interacts with the previous one detected on the chromosome 5 distal region. Conclusion Our results demonstrate that stratifying genetic population by molecular phenotypes followed by QTL analysis on various subtypes can lead to identification of novel and interacting QTL.

Published
2011
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49. A factor model to analyze heterogeneity in gene expression

Author

Le Mignon Guillaume, Blum Yuna, Lagarrigue Sandrine, and Causeur David

Subjects
Computer applications to medicine. Medical informatics, R858-859.7, Biology (General), QH301-705.5
Abstract

Abstract Background Microarray technology allows the simultaneous analysis of thousands of genes within a single experiment. Significance analyses of transcriptomic data ignore the gene dependence structure. This leads to correlation among test statistics which affects a strong control of the false discovery proportion. A recent method called FAMT allows capturing the gene dependence into factors in order to improve high-dimensional multiple testing procedures. In the subsequent analyses aiming at a functional characterization of the differentially expressed genes, our study shows how these factors can be used both to identify the components of expression heterogeneity and to give more insight into the underlying biological processes. Results The use of factors to characterize simple patterns of heterogeneity is first demonstrated on illustrative gene expression data sets. An expression data set primarily generated to map QTL for fatness in chickens is then analyzed. Contrarily to the analysis based on the raw data, a relevant functional information about a QTL region is revealed by factor-adjustment of the gene expressions. Additionally, the interpretation of the independent factors regarding known information about both experimental design and genes shows that some factors may have different and complex origins. Conclusions As biological information and technological biases are identified in what was before simply considered as statistical noise, analyzing heterogeneity in gene expression yields a new point of view on transcriptomic data.

Published
2010
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50. Additional file 2: Figure S1. of Relationships between gut microbiota, plasma metabolites, and metabolic syndrome traits in the METSIM cohort

Author

Org, Elin, Blum, Yuna, Kasela, Silva, Mehrabian, Margarete, Kuusisto, Johanna, Kangas, Antti, Soininen, Pasi, Zeneng Wang, Ala-Korpela, Mika, Hazen, Stanley, Laakso, Markku, and Aldons Lusis

Abstract

Variability of gut microbiota composition in METSIM samples. Figure S2. Association of bacterial diversity and richness measures with traits. Figure S3. Associations of OTUs with fasting blood levels of metabolites. Figure S4. Glutamine and branched chain amino acid (BCAA) levels. Figure S5. Correlation heatmap demonstrating the association between the metabolic traits and fasting TMAO concentrations. Figure S6. Gut microbiota profile in obese and T2D. Figure S7. Comparison between pre-T2D and NGS OTU networks. (PDF 3209 kb)

Published
2017
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