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5. An integrated omics approach highlights how epigenetic events can explain and predict response to neoadjuvant chemotherapy and bevacizumab in breast cancer.

Author

Fleischer, Thomas, Haugen, Mads Haugland, Ankill, Jørgen, Silwal‐Pandit, Laxmi, Børresen‐Dale, Anne‐Lise, Hedenfalk, Ingrid, Hatschek, Thomas, Tost, Jörg, Engebraaten, Olav, and Kristensen, Vessela N.

Abstract

Treatment with the anti‐angiogenic drug bevacizumab in addition to chemotherapy has shown efficacy for breast cancer in some clinical trials, but better biomarkers are needed to optimally select patients for treatment. Here, we present an omics approach where DNA methylation profiles are integrated with gene expression and results from proteomic data in breast cancer patients to predict response to therapy and pinpoint response‐related epigenetic events. Fresh‐frozen tumor biopsies taken before, during, and after treatment from human epidermal growth factor receptor 2 negative non‐metastatic patients receiving neoadjuvant chemotherapy with or without bevacizumab were subjected to molecular profiling. Here, we report that DNA methylation at enhancer CpGs related to cell cycle regulation can predict response to chemotherapy and bevacizumab for the estrogen receptor positive subset of patients (AUC = 0.874), and we validated this observation in an independent patient cohort with a similar treatment regimen (AUC = 0.762). Combining the DNA methylation scores with the scores from a previously published protein signature resulted in a slight increase in the prediction performance (AUC = 0.784). We also show that tumors receiving the combination treatment underwent more extensive epigenetic alterations. Finally, we performed an integrative expression–methylation quantitative trait loci analysis on alterations in DNA methylation and gene expression levels, showing that the epigenetic alterations that occur during treatment are different between responders and non‐responders and that these differences may be explained by the proliferation–epithelial‐to‐mesenchymal transition axis through the activity of grainyhead like transcription factor 2. Using tumor purity computed from copy number data, we developed a method for estimating cancer cell‐specific methylation to confirm that the association to response reflects DNA methylation in cancer cells. Taken together, these results support the potential for clinical benefit of the addition of bevacizumab to chemotherapy when administered to the correct patients. [ABSTRACT FROM AUTHOR]

Published
2024
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6. Molecular Mechanisms of Trophoblast Dysfunction Mediated by Imbalance between STOX1 Isoforms

Author

Ducat, Aurélien, Couderc, Betty, Bouter, Anthony, Biquard, Louise, Aouache, Rajaa, Passet, Bruno, Doridot, Ludivine, Cohen, Marie-Benoîte, Ribaux, Pascale, Apicella, Clara, Gaillard, Irène, Palfray, Sophia, Chen, Yulian, Vargas, Alexandra, Julé, Amélie, Frelin, Léo, Cocquet, Julie, San Martin, Camino Ruano, Jacques, Sébastien, Busato, Florence, Tost, Jorg, Méhats, Céline, Laissue, Paul, Vilotte, Jean-Luc, Miralles, Francisco, and Vaiman, Daniel

Published
2020
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7. DNA Methylation in Newborns and Maternal Smoking in Pregnancy: Genome-wide Consortium Meta-analysis

Author

Joubert, Bonnie R, Felix, Janine F, Yousefi, Paul, Bakulski, Kelly M, Just, Allan C, Breton, Carrie, Reese, Sarah E, Markunas, Christina A, Richmond, Rebecca C, Xu, Cheng-Jian, Küpers, Leanne K, Oh, Sam S, Hoyo, Cathrine, Gruzieva, Olena, Söderhäll, Cilla, Salas, Lucas A, Baïz, Nour, Zhang, Hongmei, Lepeule, Johanna, Ruiz, Carlos, Ligthart, Symen, Wang, Tianyuan, Taylor, Jack A, Duijts, Liesbeth, Sharp, Gemma C, Jankipersadsing, Soesma A, Nilsen, Roy M, Vaez, Ahmad, Fallin, M Daniele, Hu, Donglei, Litonjua, Augusto A, Fuemmeler, Bernard F, Huen, Karen, Kere, Juha, Kull, Inger, Munthe-Kaas, Monica Cheng, Gehring, Ulrike, Bustamante, Mariona, Saurel-Coubizolles, Marie José, Quraishi, Bilal M, Ren, Jie, Tost, Jörg, Gonzalez, Juan R, Peters, Marjolein J, Håberg, Siri E, Xu, Zongli, van Meurs, Joyce B, Gaunt, Tom R, Kerkhof, Marjan, Corpeleijn, Eva, Feinberg, Andrew P, Eng, Celeste, Baccarelli, Andrea A, Neelon, Sara E Benjamin, Bradman, Asa, Merid, Simon Kebede, Bergström, Anna, Herceg, Zdenko, Hernandez-Vargas, Hector, Brunekreef, Bert, Pinart, Mariona, Heude, Barbara, Ewart, Susan, Yao, Jin, Lemonnier, Nathanaël, Franco, Oscar H, Wu, Michael C, Hofman, Albert, McArdle, Wendy, Van der Vlies, Pieter, Falahi, Fahimeh, Gillman, Matthew W, Barcellos, Lisa F, Kumar, Ashish, Wickman, Magnus, Guerra, Stefano, Charles, Marie-Aline, Holloway, John, Auffray, Charles, Tiemeier, Henning W, Smith, George Davey, Postma, Dirkje, Hivert, Marie-France, Eskenazi, Brenda, Vrijheid, Martine, Arshad, Hasan, Antó, Josep M, Dehghan, Abbas, Karmaus, Wilfried, Annesi-Maesano, Isabella, Sunyer, Jordi, Ghantous, Akram, Pershagen, Göran, Holland, Nina, Murphy, Susan K, DeMeo, Dawn L, Burchard, Esteban G, Ladd-Acosta, Christine, Snieder, Harold, and Nystad, Wenche

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Health Sciences, Genetics, Human Genome, Prevention, Tobacco Smoke and Health, Tobacco, Perinatal Period - Conditions Originating in Perinatal Period, Pediatric, Clinical Research, 2.1 Biological and endogenous factors, Reproductive health and childbirth, Respiratory, Good Health and Well Being, Asthma, Child, Child, Preschool, Chromosome Mapping, Cleft Lip, Cleft Palate, DNA Methylation, Epigenesis, Genetic, Female, Genetic Association Studies, Humans, Infant, Infant, Newborn, Pregnancy, Smoking, White People, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Epigenetic modifications, including DNA methylation, represent a potential mechanism for environmental impacts on human disease. Maternal smoking in pregnancy remains an important public health problem that impacts child health in a myriad of ways and has potential lifelong consequences. The mechanisms are largely unknown, but epigenetics most likely plays a role. We formed the Pregnancy And Childhood Epigenetics (PACE) consortium and meta-analyzed, across 13 cohorts (n = 6,685), the association between maternal smoking in pregnancy and newborn blood DNA methylation at over 450,000 CpG sites (CpGs) by using the Illumina 450K BeadChip. Over 6,000 CpGs were differentially methylated in relation to maternal smoking at genome-wide statistical significance (false discovery rate, 5%), including 2,965 CpGs corresponding to 2,017 genes not previously related to smoking and methylation in either newborns or adults. Several genes are relevant to diseases that can be caused by maternal smoking (e.g., orofacial clefts and asthma) or adult smoking (e.g., certain cancers). A number of differentially methylated CpGs were associated with gene expression. We observed enrichment in pathways and processes critical to development. In older children (5 cohorts, n = 3,187), 100% of CpGs gave at least nominal levels of significance, far more than expected by chance (p value < 2.2 × 10(-16)). Results were robust to different normalization methods used across studies and cell type adjustment. In this large scale meta-analysis of methylation data, we identified numerous loci involved in response to maternal smoking in pregnancy with persistence into later childhood and provide insights into mechanisms underlying effects of this important exposure.

Published
2016

8. DNA hypomethylation of the host tree impairs interaction with mutualistic ectomycorrhizal fungus

Author

Conseil Régional du Centre-Val de Loire, Department of Energy (US), Kohler, Annegret [0000-0002-9575-9567], Sow, Mamadou Dia [0000-0002-2815-4939], Delaunay, Alain [0000-0002-2519-5380], Fauchery, Laure [0000-0002-2571-0274], Barry, Kerrie W. [0000-0002-8999-6785], Keymanesh, Keykhosrow [0000-0001-6019-9443], Singan, Vasanth [0000-0002-9983-5707], Grigoriev, Igor [0000-0002-3136-8903], Fichot, Régis [0000-0001-5527-4103], Conde, Daniel [0000-0001-8362-4190], Perales, Mariano [0000-0002-7351-8439], Tost, Jörg [0000-0002-2683-0817], Martin, Francis M. [0000-0002-4737-3715], Allona, Isabel [0000-0002-7012-2850], Strauss, Steven H. [0000-0001-9670-3082], Veneault-Fourrey, Claire [0000-0001-9778-2659], Maury, Stéphane 0000-0003-0481-0847], Vigneaud, Julien, Kohler, Annegret, Sow, Mamadou Dia, Delaunay, Alain, Fauchery, Laure, Guinet, Frederic, Daviaud, Christian, Barry, Kerrie W., Keymanesh, Keykhosrow, Johnson, Jenifer, Singan, Vasanth, Grigoriev, Igor, Fichot, Régis, Conde, Daniel, Perales, Mariano, Tost, Jörg, Martin, Francis M., Allona, Isabel, Strauss, Steven H., Veneault-Fourrey, Claire, Maury, Stéphane, Conseil Régional du Centre-Val de Loire, Department of Energy (US), Kohler, Annegret [0000-0002-9575-9567], Sow, Mamadou Dia [0000-0002-2815-4939], Delaunay, Alain [0000-0002-2519-5380], Fauchery, Laure [0000-0002-2571-0274], Barry, Kerrie W. [0000-0002-8999-6785], Keymanesh, Keykhosrow [0000-0001-6019-9443], Singan, Vasanth [0000-0002-9983-5707], Grigoriev, Igor [0000-0002-3136-8903], Fichot, Régis [0000-0001-5527-4103], Conde, Daniel [0000-0001-8362-4190], Perales, Mariano [0000-0002-7351-8439], Tost, Jörg [0000-0002-2683-0817], Martin, Francis M. [0000-0002-4737-3715], Allona, Isabel [0000-0002-7012-2850], Strauss, Steven H. [0000-0001-9670-3082], Veneault-Fourrey, Claire [0000-0001-9778-2659], Maury, Stéphane 0000-0003-0481-0847], Vigneaud, Julien, Kohler, Annegret, Sow, Mamadou Dia, Delaunay, Alain, Fauchery, Laure, Guinet, Frederic, Daviaud, Christian, Barry, Kerrie W., Keymanesh, Keykhosrow, Johnson, Jenifer, Singan, Vasanth, Grigoriev, Igor, Fichot, Régis, Conde, Daniel, Perales, Mariano, Tost, Jörg, Martin, Francis M., Allona, Isabel, Strauss, Steven H., Veneault-Fourrey, Claire, and Maury, Stéphane

Abstract

Ectomycorrhizas are an intrinsic component of tree nutrition and responses to environmental variations. How epigenetic mechanisms might regulate these mutualistic interactions is unknown. By manipulating the level of expression of the chromatin remodeler DECREASE IN DNA METHYLATION 1 (DDM1) and two demethylases DEMETER-LIKE (DML) in Populus tremula × Populus alba lines, we examined how host DNA methylation modulates multiple parameters of the responses to root colonization with the mutualistic fungus Laccaria bicolor. We compared the ectomycorrhizas formed between transgenic and wild-type (WT) trees and analyzed their methylomes and transcriptomes. The poplar lines displaying lower mycorrhiza formation rate corresponded to hypomethylated overexpressing DML or RNAi-ddm1 lines. We found 86 genes and 288 transposable elements (TEs) differentially methylated between WT and hypomethylated lines (common to both OX-dml and RNAi-ddm1) and 120 genes/1441 TEs in the fungal genome suggesting a host-induced remodeling of the fungal methylome. Hypomethylated poplar lines displayed 205 differentially expressed genes (cis and trans effects) in common with 17 being differentially methylated (cis). Our findings suggest a central role of host and fungal DNA methylation in the ability to form ectomycorrhizas including not only poplar genes involved in root initiation, ethylene and jasmonate-mediated pathways, and immune response but also terpenoid metabolism.

Published
2023

9. A General Framework for Interrogation of mRNA Stability Programs Identifies RNA-Binding Proteins that Govern Cancer Transcriptomes

Author

Perron, Gabrielle, Jandaghi, Pouria, Solanki, Shraddha, Safisamghabadi, Maryam, Storoz, Cristina, Karimzadeh, Mehran, Papadakis, Andreas I., Arseneault, Madeleine, Scelo, Ghislaine, Banks, Rosamonde E., Tost, Jorg, Lathrop, Mark, Tanguay, Simon, Brazma, Alvis, Huang, Sidong, Brimo, Fadi, Najafabadi, Hamed S., and Riazalhosseini, Yasser

Published
2018
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11. Placental DNA methylation signatures of prenatal air pollution exposure and potential effects on birth outcomes: an analysis of three prospective cohorts

Author

Broséus, Lucile, Guilbert, Ariane, Hough, Ian, Kloog, Itai, Chauvaud, Anath, Seyve, Emie, Vaiman, Daniel, Heude, Barbara, Chevrier, Cécile, Tost, Jörg, Slama, Rémy, and Lepeule, Johanna

Abstract

Pregnancy air pollution exposure (PAPE) has been linked to a wide range of adverse birth and childhood outcomes, but there is a paucity of data on its influence on the placental epigenome, which can regulate the programming of physiological functions and affect child development. This study aimed to investigate the association between prenatal air pollutant exposure concentrations and changes in placental DNA methylation patterns, and to explore the potential windows of susceptibility and sex-specific alterations.

Published
2024
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13. Epigenome-Wide Associations of Placental DNA Methylation and Behavioral and Emotional Difficulties in Children at 3 Years of Age

Author

Nakamura, Aurélie, primary, Broséus, Lucile, additional, Tost, Jörg, additional, Vaiman, Daniel, additional, Martins, Silvia, additional, Keyes, Katherine, additional, Bonello, Kim, additional, Fekom, Mathilde, additional, Strandberg-Larsen, Katrine, additional, Sutter-Dallay, Anne-Laure, additional, Heude, Barbara, additional, Melchior, Maria, additional, and Lepeule, Johanna, additional

Published
2023
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16. Epigenome-Wide Associations of Placental DNA Methylation and Behavioral and Emotional Difficulties in Children at 3 Years of Age

Author

Nakamura, Aurélie, Broséus, Lucile, Tost, Jörg, Vaiman, Daniel, Martins, Silvia, Keyes, Katherine, Bonello, Kim, Fekom, Mathilde, Strandberg-Larsen, Katrine, Sutter-Dallay, Anne Laure, Heude, Barbara, Melchior, Maria, Lepeule, Johanna, Nakamura, Aurélie, Broséus, Lucile, Tost, Jörg, Vaiman, Daniel, Martins, Silvia, Keyes, Katherine, Bonello, Kim, Fekom, Mathilde, Strandberg-Larsen, Katrine, Sutter-Dallay, Anne Laure, Heude, Barbara, Melchior, Maria, and Lepeule, Johanna

Abstract

The placenta is a key organ for fetal and brain development. Its epigenome can be regarded as a biochemical record of the prenatal environment and a potential mechanism of its association with the future health of the fetus. We investigated associations between placental DNA methylation levels and child behavioral and emotional difficulties, assessed at 3 years of age using the Strengths and Difficulties Questionnaire (SDQ) in 441 mother–child dyads from the EDEN cohort. Hypothesis-driven and exploratory analyses (on differentially methylated probes (EWAS) and regions (DMR)) were adjusted for confounders, technical factors, and cell composition estimates, corrected for multiple comparisons, and stratified by child sex. Hypothesis-driven analyses showed an association of cg26703534 (AHRR) with emotional symptoms, and exploratory analyses identified two probes, cg09126090 (intergenic region) and cg10305789 (PPP1R16B), as negatively associated with peer relationship problems, as well as 33 DMRs, mostly positively associated with at least one of the SDQ subscales. Among girls, most associations were seen with emotional difficulties, whereas in boys, DMRs were as much associated with emotional than behavioral difficulties. This study provides the first evidence of associations between placental DNA methylation and child behavioral and emotional difficulties. Our results suggest sex-specific associations and might provide new insights into the mechanisms of neurodevelopment. Keywords: EWAS; DNA methylation; DOHAD; placenta; child behavior; pregnancy; epidemiology, The placenta is a key organ for fetal and brain development. Its epigenome can be regarded as a biochemical record of the prenatal environment and a potential mechanism of its association with the future health of the fetus. We investigated associations between placental DNA methylation levels and child behavioral and emotional difficulties, assessed at 3 years of age using the Strengths and Difficulties Questionnaire (SDQ) in 441 mother–child dyads from the EDEN cohort. Hypothesis-driven and exploratory analyses (on differentially methylated probes (EWAS) and regions (DMR)) were adjusted for confounders, technical factors, and cell composition estimates, corrected for multiple comparisons, and stratified by child sex. Hypothesis-driven analyses showed an association of cg26703534 (AHRR) with emotional symptoms, and exploratory analyses identified two probes, cg09126090 (intergenic region) and cg10305789 (PPP1R16B), as negatively associated with peer relationship problems, as well as 33 DMRs, mostly positively associated with at least one of the SDQ subscales. Among girls, most associations were seen with emotional difficulties, whereas in boys, DMRs were as much associated with emotional than behavioral difficulties. This study provides the first evidence of associations between placental DNA methylation and child behavioral and emotional difficulties. Our results suggest sex-specific associations and might provide new insights into the mechanisms of neurodevelopment.

Published
2023

17. Application of Genomic Sequencing to Refine Patient Stratification for Adjuvant Therapy in Renal Cell Carcinoma

Author

Vasudev, Naveen S., primary, Scelo, Ghislaine, additional, Glennon, Kate I., additional, Wilson, Michelle, additional, Letourneau, Louis, additional, Eveleigh, Robert, additional, Nourbehesht, Nazanin, additional, Arseneault, Madeleine, additional, Paccard, Antoine, additional, Egevad, Lars, additional, Viksna, Juris, additional, Celms, Edgars, additional, Jackson, Sharon M., additional, Abedi-Ardekani, Behnoush, additional, Warren, Anne Y., additional, Selby, Peter J., additional, Trainor, Sebastian, additional, Kimuli, Michael, additional, Cartledge, Jon, additional, Soomro, Naeem, additional, Adeyoju, Adebanji, additional, Patel, Poulam M., additional, Wozniak, Magdalena B., additional, Holcatova, Ivana, additional, Brisuda, Antonin, additional, Janout, Vladimir, additional, Chanudet, Estelle, additional, Zaridze, David, additional, Moukeria, Anush, additional, Shangina, Oxana, additional, Foretova, Lenka, additional, Navratilova, Marie, additional, Mates, Dana, additional, Jinga, Viorel, additional, Bogdanovic, Ljiljana, additional, Kovacevic, Bozidar, additional, Cambon-Thomsen, Anne, additional, Bourque, Guillaume, additional, Brazma, Alvis, additional, Tost, Jörg, additional, Brennan, Paul, additional, Lathrop, Mark, additional, Riazalhosseini, Yasser, additional, and Banks, Rosamonde E., additional

Published
2023
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18. DNA hypomethylation of the host tree impairs interaction with mutualistic ectomycorrhizal fungus

Author

Vigneaud, Julien, primary, Kohler, Annegret, additional, Sow, Mamadou Dia, additional, Delaunay, Alain, additional, Fauchery, Laure, additional, Guinet, Frederic, additional, Daviaud, Christian, additional, Barry, Kerrie W., additional, Keymanesh, Keykhosrow, additional, Johnson, Jenifer, additional, Singan, Vasanth, additional, Grigoriev, Igor, additional, Fichot, Régis, additional, Conde, Daniel, additional, Perales, Mariano, additional, Tost, Jörg, additional, Martin, Francis M., additional, Allona, Isabel, additional, Strauss, Steven H., additional, Veneault‐Fourrey, Claire, additional, and Maury, Stéphane, additional

Published
2023
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22. Germline and somatic genetic variations of TNFAIP3 in lymphoma complicating primary Sjögren's syndrome

Author

Nocturne, Gaetane, Boudaoud, Saida, Miceli-Richard, Corinne, Viengchareun, Say, Lazure, Thierry, Nititham, Joanne, Taylor, Kimberly E., Ma, Averil, Busato, Florence, Melki, Judith, Lessard, Christopher J., Sivils, Kathy L., Dubost, Jean-Jacques, Hachulla, Eric, Gottenberg, Jacques Eric, Lombès, Marc, Tost, Jorg, Criswell, Lindsey A., and Mariette, Xavier

Published
2013
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24. Abstract LB113: Genomic classification to refine prognosis in clear cell renal cell carcinoma

Author

Glennon, Kate I., primary, Vasudev, Naveen S., additional, Scelo, Ghislaine, additional, Wilson, Michelle, additional, Letourneau, Louis, additional, Eveleigh, Robert, additional, Nourbehesht, Nazanin, additional, Arseneault, Madeleine, additional, Paccard, Antoine, additional, Egevad, Lars, additional, Viksna, Juris, additional, Celms, Edgars, additional, Jackson, Sharon M., additional, Abedi-Ardekani, Behnoush, additional, Warren, Anne Y., additional, Selby, Peter J., additional, Trainor, Sebastian, additional, Kimuli, Michael, additional, Soomro, Naeem, additional, Adeyoju, Adebanji, additional, Patel, Poulam, additional, Wozniak, Magdalena B., additional, Holcatova, Ivana, additional, Brisuda, Antonin, additional, Janout, Vladimir, additional, Chanudet, Estelle, additional, Zaridze, David, additional, Moukeria, Anush, additional, Shangina, Oxana, additional, Foretova, Lenka, additional, Navratilova, Marie, additional, Mates, Dana, additional, Jinga, Viorel, additional, Bogdanovic, Ljiljana, additional, Kovacevic, Bozidar, additional, Cambon-Thomsen, Anne, additional, Bourque, Guillaume, additional, Brazma, Alvis, additional, Tost, Jörg, additional, Brennan, Paul, additional, Lathrop, Mark, additional, Riazalhosseini, Yasser, additional, and Banks, Rosamonde E., additional

Published
2022
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27. Pregnancy exposure to phthalates and DNA methylation in male placenta — An epigenome-wide association study

Author

Jedynak, Paulina, primary, Tost, Jörg, additional, Calafat, Antonia M., additional, Bourova-Flin, Ekaterina, additional, Broséus, Lucile, additional, Busato, Florence, additional, Forhan, Anne, additional, Heude, Barbara, additional, Jakobi, Milan, additional, Schwartz, Joel, additional, Slama, Rémy, additional, Vaiman, Daniel, additional, Lepeule, Johanna, additional, and Philippat, Claire, additional

Published
2022
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28. Additional file 1 of DNA methylation changes in response to neoadjuvant chemotherapy are associated with breast cancer survival

Author

Pedersen, Christine Aaserød, Cao, Maria Dung, Fleischer, Thomas, Rye, Morten B., Knappskog, Stian, Eikesdal, Hans Petter, Lønning, Per Eystein, Tost, Jörg, Kristensen, Vessela N., Tessem, May-Britt, Giskeødegård, Guro F., and Bathen, Tone F.

Subjects
Pharmacology, FOS: Biological sciences, FOS: Clinical medicine, Immunology, Genetics, Medicine, Plant Biology, Cell Biology, Molecular Biology, Cancer
Abstract

Additional file 1. A document displaying supplementary figures.

Published
2022
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29. Additional file 1 of Maternal blood pressure associates with placental DNA methylation both directly and through alterations in cell-type composition

Author

Broséus, Lucile, Vaiman, Daniel, Tost, Jörg, Martin, Camino Ruano San, Jacobi, Milan, Schwartz, Joel D., Béranger, Rémi, Slama, Rémy, Heude, Barbara, and Lepeule, Johanna

Abstract

Additional file 1: Supplementary methods and figures S1-S7. S1 - Workflow of DNA methylation data pre-processing; S2 - Overview of blood pressure data; S3 - Reference placental cell-type composition observed in the EDEN cohort; S4 - Pearson correlation between DMR effect sizes; S5.A - Sensitivity analyses for DMRs found in our main analysis; S5.B - Sensitivity analysis excluding preeclampsia cases for the DMRs found in our main analysis; S6.A - Magnitude and 95% confidence intervals of the association between each BP indicator and each reference cell-type; Figure S6.B - Compositional Principal Component Analysis performed on cell-type mixtures; S7.A - Diagnostic of the direct and indirect effect (mediated by cell-type composition) of BP on the methylation level of DMRs; S7.B - Total, direct and indirect effect of BP on the methylation level of DMRs.

Published
2022
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32. Pregnancy exposure to synthetic phenols and placental DNA methylation — An epigenome-wide association study in male infants from the EDEN cohort

Author

Jedynak, Paulina, primary, Tost, Jörg, additional, Calafat, Antonia M., additional, Bourova-Flin, Ekaterina, additional, Busato, Florence, additional, Forhan, Anne, additional, Heude, Barbara, additional, Jakobi, Milan, additional, Rousseaux, Sophie, additional, Schwartz, Joel, additional, Slama, Rémy, additional, Vaiman, Daniel, additional, Philippat, Claire, additional, and Lepeule, Johanna, additional

Published
2021
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36. Additional file 1 of Crosstalk between microRNA expression and DNA methylation drives the hormone-dependent phenotype of breast cancer

Author

Aure, Miriam Ragle, Fleischer, Thomas, Bjørklund, Sunniva, Ankill, Jørgen, Castro-Mondragon, Jaime A., Anne-Lise Børresen-Dale, Tost, Jörg, Sahlberg, Kristine K., Mathelier, Anthony, Tekpli, Xavier, and Kristensen, Vessela N.

Abstract

Additional file 1: Fig. S1. Flowchart describing data and the different steps of the analysis leading to the identification of 89,118 miRNA-methylation Quantitative Trait Loci (mimQTLs). Examples of negative and positive correlation between methylation at a CpG and expression of a miRNA are shown as scatterplots at the bottom. Fig. S2. Overview of the 89,118 miRNA-CpG associations found significant in both cohorts. The scatterplots show a) the –log10(Bonferroni-adjusted Spearman correlation p-values) of Oslo2 (x-axis) vs. TCGA (y-axis); b) Spearman correlation coefficients in Oslo2 (x-axis) vs. TCGA (y-axis). The histograms show the distribution of the correlation coefficients (Spearman’s rho) of all significant miRNA-CpG correlations in the Oslo2 (c) and TCGA (d) cohorts. Fig. S3. Number of associations and genomic positions of mimQTL miRNAs and CpGs. a) Barplot showing the number of negative (neg) and positive (pos) CpG correlations (cor) for the three different miRNA clusters. b) mimQTL Manhattan plot with genomic coordinates of CpGs (black or gray) and miRNAs (green) displayed along the x-axis, with the negative logarithm of the Bonferroni-corrected Spearman correlation p-value from Oslo2 on the y-axis. Each dot on the plot signifies a CpG or miRNA (CpGs are shown in two colors to distinguish the chromosomes more clearly). c) In cis mimQTL Manhattan plot displaying the chromosomal location (using the position of the CpG) along the x-axis of the 5125 mimQTLs found on the same chromosome (in cis). Each dot represents one mimQTL which is color-coded according to negative (black) or positive (green) miRNA-CpG correlation. The y-axis displays the negative logarithm of the Bonferroni-corrected Spearman correlation p-value from Oslo2. Fig. S4. Barplots showing the number of associations per miRNA or CpG. a) Barplot showing the number of CpG associations per miRNA (n = 119). Note that the y-axis is on log scale. b) Barplot showing the number of miRNA associations per CpG (n = 26,746). Fig. S5. Density plots showing the degree of CpG co-methylation or miRNA co-expression between cluster members (see Fig. 1 and Additional file 3 a, b) calculated by Spearman correlation. a) Correlation between CpG cluster members in the Oslo2 data. b) Correlation between CpG cluster members in the TCGA data. c) Correlation between miRNA cluster members in the Oslo2 data. d) Correlation between miRNA cluster members in the TCGA data. The dotted lines represent density plots of corresponding correlations expected by chance, i.e. correlations observed after randomly permuting the same data before performing correlation analyses. Fig. S6. Density plots showing the distribution of Spearman correlation coefficients between miRNA expression and selected variables for members of each of the miRNA clusters. a, b) miRNA expression-immune infiltration score [34] correlations for the Oslo2 (a) and TCGA (b) cohorts. c, d) miRNA expression-fibroblast infiltration score [35] correlations for the Oslo2 (c) and TCGA (d) cohorts. e, f) miRNA expression-ESR1 mRNA expression correlations for the Oslo2 (e) and TCGA (f) cohorts. Fig. S7. Heatmaps showing hierarchical clustering of miRNA expression levels (rows) from tumors (columns) of the Oslo2 (top) and TCGA (bottom) cohort. Clustering was performed using Euclidean distance and average linkage. Tumors are annotated with the following clinical/molecular classifications: PAM50 molecular subtypes (Luminal A (LumA), Luminal B (LumB), Basal-like (Basal), HER2-enriched (Her2), Normal-like (Normal); Lymphocyte infiltration (LI) group where tumors were divided into quartiles: 1 (low) – 4 (high); Fibroblast infiltration group (Fibro) where tumors were divided into quartiles: 1 (low) – 4 (high); Human epidermal growth factor receptor 2 (HER2) status; Estrogen receptor (ER) status. a, b) Clustering of miRNA cluster A expression (n = 23); c, d) Clustering of miRNA cluster B expression (n = 59); e, f) Clustering of miRNA cluster C expression (n = 37). Fig. S8. Heatmaps showing hierarchical clustering of methylation levels of CpG cluster 1 (a; n = 14,040) and CpG cluster 2 (b; n = 12,706) in the TCGA cohort (CpGs in rows and tumors in columns). Clustering was performed using Euclidean distance and average linkage. Tumors are annotated with the following clinical/molecular classifications: PAM50 molecular subtypes (Luminal A (LumA), Luminal B (LumB), Basal-like (Basal), HER2-enriched (Her2), Normal-like (Normal); Lymphocyte infiltration (LI) group where tumors were divided into quartiles: 1 (low) – 4 (high); Human epidermal growth factor receptor 2 (HER2) status; Estrogen receptor (ER) status. The CpGs are annotated according to overlap with regions annotated as “active intergenic enhancer” from ChromHMM of subtype-specific cell lines [37] with corresponding subtype colors. Fig. S9. Boxplot showing average DNA methylation of CpGs from cluster 1 in PAM50 subtypes of the Oslo2 cohort (Luminal A (LumA), Luminal B (LumB), Basal-like (Basal), HER2-enriched (Her2)). b) Boxplot showing average DNA methylation of CpGs from cluster 2 in the TCGA cohort when tumors were separated into quartile lymphocyte infiltration groups from low (1) to high (4) infiltration. c) Boxplot showing average DNA methylation of CpGs from cluster 2 in normal breast tissue (reduction mammoplasty, n = 17) or estrogen receptor (ER) positive (pos) or negative (neg) tumors of the Oslo2 cohort. d) Boxplot showing average DNA methylation of CpGs from cluster 2 in normal breast tissue (normal adjacent breast tissue, n = 97) or ER positive or negative tumors of the TCGA cohort. P-values resulting from Kruskal-Wallis tests indicated. Fig. S10. Boxplot showing DNA methylation of the hub CpG of miRNA cluster A (cg14270581; y-axis)) in ER positive (pos) and negative (neg) breast cancer cell lines and from different immune cell types (x-axis); B-cells, leukocytes (leuko), monocytes (mono) and T-cells. P-value resulting from Wilcoxon rank-sum test between cancer cell lines vs. immune cells is indicated. Fig. S11. Density plot showing the distribution of the Global Methylation Alteration (GMA) score in normal adjacent breast tissue (green), tumors (black) and tumors separated into estrogen receptor (ER) positive (pos) and negative (neg). Data from TCGA. Fig. S12. Top panel: Scatterplots showing on the x-axis mRNA expression of DNMT3A (left), DNMT3B (middle) and DNMT1 (right) vs. hsa-miR-29c-5p expression (y-axis) measured in 377 samples of the Oslo2 cohort. Bottom panel: Scatterplots showing on the x-axis protein expression of DNMT3A (left), DNMT3B (middle) and DNMT1 (right) vs. hsa-miR-29c-5p expression (y-axis) measured in 45 samples of the Oslo2 cohort. Each dot represents a tumor color-coded according to PAM50 subtype (Luminal A (LumA): dark blue; Luminal B (LumB): light blue; Basal-like (Basal): red; HER2-enriched (Her2): pink; Normal-like: green). Spearman correlation coefficient and p-value are indicated for each plot.

Published
2021
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37. Analysis and annotation of DNA methylation in two nonhuman primate species using the Infinium Human Methylation 450K and EPIC BeadChips

Author

Pichon, Fabien, Shen, Yimin, Busato, Florence, P Jochems, Simon, Jacquelin, Beatrice, Grand, Roger Le, Deleuze, Jean-Francois, Müller-Trutwin, Michaela, Tost, Jörg, Centre National de Recherche en Génomique Humaine (CNRGH), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Fondation Jean Dausset - Centre d’Etudes du Polymorphisme Humain [Paris] (CEPH), UFR Sciences du Vivant [Sciences] - Université Paris Cité (UFR SDV UPCité), Université Paris Cité (UPCité), HIV, Inflammation et persistance - HIV, Inflammation and Persistence, Institut Pasteur [Paris] (IP), Leiden University Medical Center (LUMC), Universiteit Leiden, Université Sorbonne Paris Cité (USPC), Infectious Diseases Models for Innovative Therapies (IDMIT), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, The authors would like to acknowledge grant support from ANRS and the institutional budget from the CNRGH. SPJ was recipient of a PhD fellowship from the University Paris Diderot, Sorbonne Paris Cité. The Infectious Disease Models and Innovative Therapies (IDMIT) center in Fontenay-aux-Roses, France, is funded by the French government’s Investissements d’Avenir program for infrastructures (PIA) under grant ANR-11-INBS-0008 and the PIA grant ANR-10-EQPX-02-01, ANR-11-INBS-0008,IDMIT,Infrastructure nationale pour la modélisation des maladies infectieuses humaines(2011), ANR-10-EQPX-0012,PHENOVIRT,Phénotypage humain et réalité virtuelle(2010), Université de Paris - UFR Sciences du Vivant [Sciences] (UP - UFR SDV), Université de Paris (UP), HIV, Inflammation et persistance, Institut Pasteur [Paris], Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université Paris Diderot, Sorbonne Paris Cité, Paris, France, and Université Paris Diderot - Paris 7 (UPD7)

Subjects
chlorocebus, Genome, DNA methylation, [SDV]Life Sciences [q-bio], macaca, Molecular Sequence Annotation, Macaca mulatta, 450K, African green monkey, Nucleic Acid Probes, annotation, vervet, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Chlorocebus aethiops, Animals, Humans, CpG Islands, Infinium, monkey, EPIC, microarray, Oligonucleotide Array Sequence Analysis, rhesus macaque
Abstract

International audience; Aim: Nonhuman primates are essential for research on many human diseases. The Infinium Human Methylation450/EPIC BeadChips are popular tools for the study of the methylation state across the human genome at affordable cost. Methods: We performed a precise evaluation and re-annotation of the BeadChip probes for the analysis of genome-wide DNA methylation patterns in rhesus macaques and African green monkeys through in silico analyses combined with functional validation by pyrosequencing. Results: Up to 165,847 of the 450K and 261,545 probes of the EPIC BeadChip can be reliably used. The annotation files are provided in a format compatible with a variety of standard bioinformatic pipelines. Conclusion: Our study will facilitate high-throughput DNA methylation analyses in Macaca mulatta and Chlorocebus sabaeus.

Published
2021
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38. RNAi suppression of DNA methylation affects the drought stress response and genome integrity in transgenic poplar

Author

Sow, Mamadou D., primary, Le Gac, Anne‐Laure, additional, Fichot, Régis, additional, Lanciano, Sophie, additional, Delaunay, Alain, additional, Le Jan, Isabelle, additional, Lesage‐Descauses, Marie‐Claude, additional, Citerne, Sylvie, additional, Caius, Jose, additional, Brunaud, Véronique, additional, Soubigou‐Taconnat, Ludivine, additional, Cochard, Hervé, additional, Segura, Vincent, additional, Chaparro, Cristian, additional, Grunau, Christoph, additional, Daviaud, Christian, additional, Tost, Jörg, additional, Brignolas, Franck, additional, Strauss, Steven H., additional, Mirouze, Marie, additional, and Maury, Stéphane, additional

Published
2021
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39. Developmental Methylome of the Medicinal Plant Catharanthus roseus Unravels the Tissue-Specific Control of the Monoterpene Indole Alkaloid Pathway by DNA Methylation

Author

Bernonville, Thomas Dugé de, Maury, Stéphane, Delaunay, Alain, Daviaud, Christian, Chaparro, Cristian, Tost, Jörg, O’Connor, Sarah Ellen, Courdavault, Vincent, Biomolécules et biotechnologies végétales (BBV EA 2106), Université de Tours, Laboratoire de Biologie des Ligneux et des Grandes Cultures (LBLGC), Université d'Orléans (UO)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire d'Epigénétique et d'Environnement [Evry] (CNG - CEA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de Genotypage-Institut de Génomique [Evry], Interactions Hôtes-Pathogènes-Environnements (IHPE), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Perpignan Via Domitia (UPVD), Max Planck Institute for Chemical Ecology, Max-Planck-Gesellschaft, Université de Tours (UT), and Université de Perpignan Via Domitia (UPVD)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)

Subjects
plant specialized metabolism, Plants, Medicinal, DNA methylation, Whole Genome Sequencing, epigenetics, Catharanthus, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], folivory, alkaloids, Article, Enzymes, Indole Alkaloids, lcsh:Chemistry, Epigenome, lcsh:Biology (General), lcsh:QD1-999, Gene Expression Regulation, Plant, Plant Cells, Monoterpenes, Photosynthesis, organs, lcsh:QH301-705.5, Plant Proteins, Signal Transduction, Transcription Factors
Abstract

International audience; Catharanthus roseus produces a wide spectrum of monoterpene indole alkaloids (MIAs). MIA biosynthesis requires a tightly coordinated pathway involving more than 30 enzymatic steps that are spatio-temporally and environmentally regulated so that some MIAs specifically accumulate in restricted plant parts. The first regulatory layer involves a complex network of transcription factors from the basic Helix Loop Helix (bHLH) or AP2 families. In the present manuscript, we investigated whether an additional epigenetic layer could control the organ-, developmental-and environmental-specificity of MIA accumulation. We used Whole-Genome Bisulfite Sequencing (WGBS) together with RNA-seq to identify differentially methylated and expressed genes among nine samples reflecting different plant organs and experimental conditions. Tissue specific gene expression was associated with specific methylation signatures depending on cytosine contexts and gene parts. Some genes encoding key enzymatic steps from the MIA pathway were found to be simultaneously differentially expressed and methylated in agreement with the corresponding MIA accumulation. In addition, we found that transcription factors were strikingly concerned by DNA methylation variations. Altogether, our integrative analysis supports an epigenetic regulation of specialized metabolisms in plants and more likely targeting transcription factors which in turn may control the expression of enzyme-encoding genes.

Published
2020
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40. RNAi suppression of DNA methylation affects the drought stress response and genome integrity in transgenic poplar

Author

Sow, Mamadou D., Le Gac, Anne‐laure, Fichot, Régis, Lanciano, Sophie, Delaunay, Alain, Le Jan, Isabelle, Lesage‐descauses, Marie‐claude, Citerne, Sylvie, Caius, Jose, Brunaud, Véronique, Soubigou‐taconnat, Ludivine, Cochard, Hervé, Segura, Vincent, Chaparro, Cristian, Grunau, Christoph, Daviaud, Christian, Tost, Jörg, Brignolas, Franck, Strauss, Steven H., Mirouze, Marie, Maury, Stéphane, Sow, Mamadou D., Le Gac, Anne‐laure, Fichot, Régis, Lanciano, Sophie, Delaunay, Alain, Le Jan, Isabelle, Lesage‐descauses, Marie‐claude, Citerne, Sylvie, Caius, Jose, Brunaud, Véronique, Soubigou‐taconnat, Ludivine, Cochard, Hervé, Segura, Vincent, Chaparro, Cristian, Grunau, Christoph, Daviaud, Christian, Tost, Jörg, Brignolas, Franck, Strauss, Steven H., Mirouze, Marie, and Maury, Stéphane

Abstract

rees are long-lived organisms that continuously adapt to their environments, a process in which epigenetic mechanisms are likely to play a key role. Via downregulation of the chromatin remodeler DECREASED IN DNA METHYLATION 1 (DDM1) in poplar (Populus tremula × Populus alba) RNAi lines, we examined how DNA methylation coordinates genomic and physiological responses to moderate water deficit. We compared the growth and drought response of two RNAi-ddm1 lines to wild-type (WT) trees under well-watered and water deficit/rewatering conditions, and analyzed their methylomes, transcriptomes, mobilomes and phytohormone contents in the shoot apical meristem. The RNAi-ddm1 lines were more tolerant to drought-induced cavitation but did not differ in height or stem diameter growth. About 5000 differentially methylated regions were consistently detected in both RNAi-ddm1 lines, colocalizing with 910 genes and 89 active transposable elements. Under water deficit conditions, 136 differentially expressed genes were found, including many involved in phytohormone pathways; changes in phytohormone concentrations were also detected. Finally, the combination of hypomethylation and drought led to the mobility of two transposable elements. Our findings suggest major roles for DNA methylation in regulation of genes involved in hormone-related stress responses, and the maintenance of genome integrity through repression of transposable elements.

Published
2021
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41. Comprehensive miRNome-Wide Profiling in a Neuronal Cell Model of Synucleinopathy Implies Involvement of Cell Cycle Genes

Author

Findeiss, Elisabeth, primary, Schwarz, Sigrid C., additional, Evsyukov, Valentin, additional, Rösler, Thomas W., additional, Höllerhage, Matthias, additional, Chakroun, Tasnim, additional, Nykänen, Niko-Petteri, additional, Shen, Yimin, additional, Wurst, Wolfgang, additional, Kohl, Michael, additional, Tost, Jörg, additional, and Höglinger, Günter U., additional

Published
2021
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44. Association between dietary patterns reflecting one-carbon metabolism nutrients intake before pregnancy and placental DNA methylation.

Author

Lecorguillé, Marion, Charles, Marie-Aline, Lepeule, Johanna, Lioret, Sandrine, de Lauzon-Guillain, Blandine, Forhan, Anne, Tost, Jörg, Suderman, Matthew, and Heude, Barbara

Subjects
DNA methylation, NUTRITIONAL status, PLACENTA, VITAMIN B complex, FOOD consumption
Abstract

The preconception period represents an important window for foetal and epigenetic programming. Some micronutrients (B vitamins, choline, betaine, methionine) implicated in one-carbon metabolism (OCM) are essential for major epigenetic processes that take place in early pregnancy. However, few studies have evaluated the implication of the micronutrients in placental DNA methylation. We investigated whether intake of OCM nutrients in the year before pregnancy was associated with placental DNA methylation in the EDEN mother–child cohort. Maternal dietary intake was assessed with a food-frequency questionnaire. Three dietary patterns, 'varied and balanced diet,' 'vegetarian tendency,' and 'bread and starchy food,' were used to characterize maternal OCM dietary intake. The Illumina Infinium HumanMethylation450 BeadChip was used to measure placental DNA methylation of 573 women included in the analyses. We evaluated the association of dietary patterns with global DNA methylation. Then, we conducted an agnostic epigenome-wide association study (EWAS) and investigated differentially methylated regions (DMRs) associated with each dietary pattern. We found no significant association between the three dietary patterns and global DNA methylation or individual CpG sites. DMR analyses highlighted associations between the 'varied and balanced' or 'vegetarian tendency' pattern and DMRs located at genes previously implicated in functions essential for embryonic development, such as neurodevelopment. The 'bread and starchy food' pattern was associated with regions related to genes whose functions involve various metabolic and cell synthesis-related processes. In mainly well-nourished French women without major deficiencies, OCM intake before pregnancy was not associated with major variation in DNA methylation. [ABSTRACT FROM AUTHOR]

Published
2022
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50. International network of cancer genome projects

Author

Hudson, Thomas J., Anderson, Warwick, Aretz, Axel, Bell, Cindy, Bernabé, Rosa R., Bhan, M. K., Calvo, Fabien, Eerola, Iiro, Gerhard, Daniela S., Guttmacher, Alan, Guyer, Mark, Hemsley, Fiona M., Jennings, Jennifer L., Kerr, David, Klatt, Peter, Kolar, Patrik, Lane, David P., Laplace, Frank, Nettekoven, Gerd, Ozenberger, Brad, Peterson, Jane, Rao, T. S., Remacle, Jacques, Schafer, Alan J., Shibata, Tatsuhiro, Stratton, Michael R., Watanabe, Koichi, Yuen, Matthew M. F., Cambon-Thomsen, Anne, Dressler, Lynn G., Joly, Yann, Kennedy, Karen L., Parker, Michael J., Romeo-Casabona, Carlos M., Wallace, Susan, Wiesner, Georgia L., Zeps, Nikolajs, Biankin, Andrew V., Chabannon, Christian, de Alava, Enrique, Ferguson, Martin L., Geary, Peter, Hayes, Neil D., Johns, Amber L., Kasprzyk, Arek, Nakagawa, Hidewaki, Piris, Miguel A., van de Vijver, Marc, Aburatani, Hiroyuki, Bayés, Mónica, Bowtell, David D.L., Campbell, Peter J., Hirst, Martin, López-Otín, Carlos, Marra, Marco, Ning, Zemin, Puente, Xose S., Ruan, Yijun, Stunnenberg, Hendrik G., Swerdlow, Harold, Velculescu, Victor E., Xue, Hong H., Yang, Liu, Spellman, Paul T., Bader, Gary D., Boutros, Paul C., Flicek, Paul, Getz, Gad, Guigó, Roderic, Guo, Guangwu, Haussler, David, Hubbard, Tim J., Jiang, Tao, Jones, Steven M., Li, Qibin, López-Bigas, Nuria, Luo, Ruibang, Muthuswamy, Lakshmi, Ouellette, Francis B. F., Pearson, John V., Quesada, Victor, Raphael, Benjamin J., Sander, Chris, Stein, Lincoln D., Stuart, Joshua M., Teague, Jon W., Totoki, Yasushi, Tsunoda, Tatsuhiko, Valencia, Alfonso, Wheeler, David A., Wu, Honglong, Zhao, Shancen, Zhou, Guangyu, Lathrop, Mark, Axton, Myles, Dyke, Stephanie O. M., Gunter, Chris, McPherson, John D., Miller, Linda J., Zhang, Junjun, Haider, Syed A., Wang, Jianxin, Yung, Christina K., Cross, Anthony, Liang, Yong, Gnaneshan, Saravanamuttu, Guberman, Jonathan, Hsu, Jack, Bobrow, Martin, Chalmers, Don R. C., Hasel, Karl W., Kaan, Terry S. H., Knoppers, Bartha M., Lowrance, William W., Masui, Tohru, Nicolás, Pilar, Rial-Sebbag, Emmanuelle, Rodriguez, Laura Lyman, Vergely, Catherine, Grimmond, Sean M., Bowtell, David D. L., Cloonan, Nicole, deFazio, Anna, Eshleman, James R., Etemadmoghadam, Dariush, Gardiner, Brooke A., Kench, James G., Scarpa, Aldo, Sutherland, Robert L., Tempero, Margaret A., Waddell, Nicola J., Wilson, Peter J., Gallinger, Steve, Tsao, Ming-Sound, Shaw, Patricia A., Petersen, Gloria M., Mukhopadhyay, Debabrata, Chin, Lynda, DePinho, Ronald A., Thayer, Sarah, Shazand, Kamran, Beck, Timothy, Sam, Michelle, Timms, Lee, Ballin, Vanessa, Ji, Jiafu, Zhang, Xiuqing, Chen, Feng, Hu, Xueda, Yang, Qi, Tian, Geng, Zhang, Lianhai, Xing, Xiaofang, Li, Xianghong, Zhu, Zhenggang, Yu, Yingyan, Yu, Jun, Yang, Huanming, Tost, Jörg, Brennan, Paul, Holcatova, Ivana, Zaridze, David, Brazma, Alvis, Egevad, Lars, Prokhortchouk, Egor, Banks, Rosamonde Elizabeth, Uhlén, Mathias, Viksna, Juris, Ponten, Fredrik, Skryabin, Konstantin, Futreal, Andrew P., Birney, Ewan, Caldas, Carlos, Reis-Filho, Jorge S., Richardson, Andrea L., Sotiriou, Christos, Birnbaum, Daniel, Blanche, Hélène, Boucher, Pascal, Boyault, Sandrine, Masson-Jacquemier, Jocelyne D., Pauporté, Iris, Pivot, Xavier, Vincent-Salomon, Anne, Tabone, Eric, Theillet, Charles, Treilleux, Isabelle, Bioulac-Sage, Paulette, Clément, Bruno, Decaens, Thomas, Degos, Françoise, Franco, Dominique, Gut, Ivo, Gut, Marta, Heath, Simon, Samuel, Didier, Thomas, Gilles, Zucman-Rossi, Jessica, Eils, Roland, Brors, Benedikt, Korbel, Jan O., Korshunov, Andrey, Landgraf, Pablo, Lehrach, Hans, Pfister, Stefan, Radlwimmer, Bernhard, Reifenberger, Guido, Taylor, Michael D., von Kalle, Christof, Majumder, Partha P., Sarin, Rajiv, Pederzoli, Paolo, Lawlor, Rita T., Delledonne, Massimo, Bardelli, Alberto, Gress, Thomas, Klimstra, David, Zamboni, Giuseppe, Nakamura, Yusuke, Kusuda, Jun, Miyano, Satoru, Kato, Kazuto, Fujimoto, Akihiro, Yoshida, Teruhiko, Campo, Elias, Estivill, Xavier, de Sanjosé, Silvia, Montserrat, Emili, González-Díaz, Marcos, Jares, Pedro, Himmelbaue, Heinz, Bea, Silvia, Aparicio, Samuel, Borg, Ake, Børresen-Dale, Anne-Lise, Foekens, John A., vanʼt Veer, Laura, Easton, Douglas F., Martin, Sancha, Compton, Carolyn C., Lander, Eric S., Penny, Robert, Shaw, Kenna M., Speed, Terence P., Vockley, Joseph G., Lichter, Peter, Barker, Anna D., Burke, Wylie, Collins, Francis S., Green, Anthony R., Hamilton, Stanley R., Kallioniemi, Olli P., Ley, Timothy J., Liu, Edison T., Lu, Youyong, Majumder, Partha, Wainwright, Brandon J., and Wilson, Richard K.

Published
2010
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