800 results on '"Beck, Stephan"'
Search Results
2. Universal penalized regression (Elastic-net) model with differentially methylated promoters for oral cancer prediction
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Das, Shantanab, Karuri, Saikat, Chakraborty, Joyeeta, Basu, Baidehi, Chandra, Aditi, Aravindan, S., Chakraborty, Anirvan, Paul, Debashis, Ray, Jay Gopal, Lechner, Matt, Beck, Stephan, Teschendorff, E. Andrew, and Chatterjee, Raghunath
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- 2024
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3. An expedited screening platform for the discovery of anti-ageing compounds in vitro and in vivo
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Lujan, Celia, Tyler, Eleanor Jane, Ecker, Simone, Webster, Amy Philomena, Stead, Eleanor Rachel, Martinez-Miguel, Victoria Eugenia, Milligan, Deborah, Garbe, James Charles, Stampfer, Martha Ruskin, Beck, Stephan, Lowe, Robert, Bishop, Cleo Lucinda, and Bjedov, Ivana
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- 2024
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4. An improved epigenetic counter to track mitotic age in normal and precancerous tissues
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Zhu, Tianyu, Tong, Huige, Du, Zhaozhen, Beck, Stephan, and Teschendorff, Andrew E.
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- 2024
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5. FORGEdb: a tool for identifying candidate functional variants and uncovering target genes and mechanisms for complex diseases
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Breeze, Charles E., Haugen, Eric, Gutierrez-Arcelus, María, Yao, Xiaozheng, Teschendorff, Andrew, Beck, Stephan, Dunham, Ian, Stamatoyannopoulos, John, Franceschini, Nora, Machiela, Mitchell J., and Berndt, Sonja I.
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- 2024
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6. Academic co-authorship is a risky game
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Lazebnik, Teddy, Beck, Stephan, and Shami, Labib
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- 2023
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7. Concepts and applications of digital twins in healthcare and medicine
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Zhang, Kang, Zhou, Hong-Yu, Baptista-Hon, Daniel T., Gao, Yuanxu, Liu, Xiaohong, Oermann, Eric, Xu, Sheng, Jin, Shengwei, Zhang, Jian, Sun, Zhuo, Yin, Yun, Razmi, Ronald M., Loupy, Alexandre, Beck, Stephan, Qu, Jia, and Wu, Joseph
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- 2024
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8. Individualized dynamic methylation-based analysis of cell-free DNA in postoperative monitoring of lung cancer
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Chen, Kezhong, Kang, Guannan, Zhang, Zhihong, Lizaso, Analyn, Beck, Stephan, Lyskjær, Iben, Chervova, Olga, Li, Bingsi, Shen, Haifeng, Wang, Chenyang, Li, Bing, Zhao, Heng, Li, Xi, Yang, Fan, Kanu, Nnennaya, and Wang, Jun
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- 2023
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9. Genomic–transcriptomic evolution in lung cancer and metastasis
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Martínez-Ruiz, Carlos, Black, James R. M., Puttick, Clare, Hill, Mark S., Demeulemeester, Jonas, Larose Cadieux, Elizabeth, Thol, Kerstin, Jones, Thomas P., Veeriah, Selvaraju, Naceur-Lombardelli, Cristina, Toncheva, Antonia, Prymas, Paulina, Rowan, Andrew, Ward, Sophia, Cubitt, Laura, Athanasopoulou, Foteini, Pich, Oriol, Karasaki, Takahiro, Moore, David A., Salgado, Roberto, Colliver, Emma, Castignani, Carla, Dietzen, Michelle, Huebner, Ariana, Al Bakir, Maise, Tanić, Miljana, Watkins, Thomas B. K., Lim, Emilia L., Al-Rashed, Ali M., Lang, Danny, Clements, James, Cook, Daniel E., Rosenthal, Rachel, Wilson, Gareth A., Frankell, Alexander M., de Carné Trécesson, Sophie, East, Philip, Kanu, Nnennaya, Litchfield, Kevin, Birkbak, Nicolai J., Hackshaw, Allan, Beck, Stephan, Van Loo, Peter, Jamal-Hanjani, Mariam, Swanton, Charles, and McGranahan, Nicholas
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- 2023
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10. Comparison and imputation-aided integration of five commercial platforms for targeted DNA methylome analysis
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Tanić, Miljana, Moghul, Ismail, Rodney, Simon, Dhami, Pawan, Vaikkinen, Heli, Ambrose, John, Barrett, James, Feber, Andrew, and Beck, Stephan
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- 2022
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11. SynthEye: Investigating the Impact of Synthetic Data on Artificial Intelligence-assisted Gene Diagnosis of Inherited Retinal Disease
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Veturi, Yoga Advaith, Woof, William, Lazebnik, Teddy, Moghul, Ismail, Woodward-Court, Peter, Wagner, Siegfried K., Cabral de Guimarães, Thales Antonio, Daich Varela, Malena, Liefers, Bart, Patel, Praveen J., Beck, Stephan, Webster, Andrew R., Mahroo, Omar, Keane, Pearse A., Michaelides, Michel, Balaskas, Konstantinos, and Pontikos, Nikolas
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- 2023
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12. Individualized tumor-informed circulating tumor DNA analysis for postoperative monitoring of non-small cell lung cancer
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Chen, Kezhong, Yang, Fan, Shen, Haifeng, Wang, Chenyang, Li, Xi, Chervova, Olga, Wu, Shuailai, Qiu, Fujun, Peng, Di, Zhu, Xin, Chuai, Shannon, Beck, Stephan, Kanu, Nnennaya, Carbone, David, Zhang, Zhihong, and Wang, Jun
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- 2023
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13. Osteosarcoma: Novel prognostic biomarkers using circulating and cell-free tumour DNA
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Lyskjær, Iben, Kara, Neesha, De Noon, Solange, Davies, Christopher, Rocha, Ana Maia, Strobl, Anna-Christina, Usher, Inga, Gerrand, Craig, Strauss, Sandra J., Schrimpf, Daniel, von Deimling, Andreas, Beck, Stephan, and Flanagan, Adrienne M.
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- 2022
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14. A pan-tissue DNA methylation atlas enables in silico decomposition of human tissue methylomes at cell-type resolution
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Zhu, Tianyu, Liu, Jacklyn, Beck, Stephan, Pan, Sun, Capper, David, Lechner, Matt, Thirlwell, Chrissie, Breeze, Charles E., and Teschendorff, Andrew E.
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- 2022
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15. Diversity in EWAS: current state, challenges, and solutions
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Breeze, Charles E., Wong, Jason Y. Y., Beck, Stephan, Berndt, Sonja I., and Franceschini, Nora
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- 2022
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16. Researcher perspectives on ethics considerations in epigenetics: an international survey
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Dupras, Charles, Knoppers, Terese, Palmour, Nicole, Beauchamp, Elisabeth, Liosi, Stamatina, Siebert, Reiner, Berner, Alison May, Beck, Stephan, Charest, Ian, and Joly, Yann
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- 2022
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17. Novel epigenetic network biomarkers for early detection of esophageal cancer
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Maity, Alok K., Stone, Timothy C., Ward, Vanessa, Webster, Amy P., Yang, Zhen, Hogan, Aine, McBain, Hazel, Duku, Margaraet, Ho, Kai Man Alexander, Wolfson, Paul, Graham, David G., Beck, Stephan, Teschendorff, Andrew E., and Lovat, Laurence B.
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- 2022
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18. Integrative analysis of 3604 GWAS reveals multiple novel cell type-specific regulatory associations
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Breeze, Charles E., Haugen, Eric, Reynolds, Alex, Teschendorff, Andrew, van Dongen, Jenny, Lan, Qing, Rothman, Nathaniel, Bourque, Guillaume, Dunham, Ian, Beck, Stephan, Stamatoyannopoulos, John, Franceschini, Nora, and Berndt, Sonja I.
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- 2022
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19. The missing diversity in human epigenomic studies
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Breeze, Charles E., Beck, Stephan, Berndt, Sonja I., and Franceschini, Nora
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- 2022
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20. The role of epigenetics in psychological resilience
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Smeeth, Demelza, Beck, Stephan, Karam, Elie G, and Pluess, Michael
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- 2021
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21. Chemotherapy induces canalization of cell state in childhood B-cell precursor acute lymphoblastic leukemia
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Turati, Virginia A., Guerra-Assunção, José Afonso, Potter, Nicola E., Gupta, Rajeev, Ecker, Simone, Daneviciute, Agne, Tarabichi, Maxime, Webster, Amy P., Ding, Chuling, May, Gillian, James, Chela, Brown, John, Conde, Lucia, Russell, Lisa J., Ancliff, Phil, Inglott, Sarah, Cazzaniga, Giovanni, Biondi, Andrea, Hall, Georgina W., Lynch, Mark, Hubank, Mike, Macaulay, Iain, Beck, Stephan, Van Loo, Peter, Jacobsen, Sten E., Greaves, Mel, Herrero, Javier, and Enver, Tariq
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- 2021
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22. South America holds the greatest diversity of native daisies (Asteraceae) in the world: an updated catalogue supporting continental-scale conservation.
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Moreira-Muñoz, Andres, Monge, Marcelo, Grossi, Mariana A., Ávila, Fabio Andrés, Morales-Fierro, Vanezza, Heiden, Gustavo, Britto, Berni, Beck, Stephan, Nakajima, Jimi N., Salgado, Vanina G., Rodrıguez-Cravero, Juan Facundo, and Gutiérrez, Diego G.
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DAISIES ,NUMBERS of species ,SPECIES diversity ,CATALOGS ,CATALOGING ,CONTINENTS ,ASTERACEAE - Abstract
Asteraceae is the world's richest plant family and is found on all continents, in environments ranging from the coast to the highest mountains. The family shows all growth forms and, as in other angiosperm families, species richness is concentrated in tropical regions. South America has the highest diversity of Asteraceae in the world, yet taxonomic and distributional knowledge gaps remain. This study compiles an updated catalog of Asteraceae native to South America, based on national and regional checklists and ongoing large-scale flora projects. The resulting checklist includes a total of 6,940 species and 564 genera native to South America to date, which represent about a quarter of the family's global diversity. Countries already considered to be megadiverse show the greatest diversity, such as Brazil with 2,095 species, followed by Peru (1,588), Argentina (1,377), and Colombia (1,244), with this diversity mainly focused on the Brazilian Highlands and the Andes. Species endemism also peaks in Brazil, but Sørensen distances reveal the Chilean flora to be eminently different from the rest of the continent. Tribes better represented in the continent are Eupatorieae, Senecioneae and Astereae, also with a remarkably presence of entirely South American subfamilies representing earliest diverging lineages of the Asteraceae, such as Barnadesioideae, Wunderlichioideae, Famatinanthoideae, and Stifftioideae. It is estimated that the discovery and description curves have not yet stabilized, and the number of species is likely to increase by 5 to 10% in the coming years, posing major challenges to continental-scale conservation. [ABSTRACT FROM AUTHOR]
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- 2024
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23. Donor whole blood DNA methylation is not a strong predictor of acute graft versus host disease in unrelated donor allogeneic haematopoietic cell transplantation.
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Webster, Amy P., Ecker, Simone, Moghul, Ismail, Xiaohong Liu, Dhami, Pawan, Marzi, Sarah, Paul, Dirk S., Kuxhausen, Michelle, Lee, Stephanie J., Spellman, Stephen R., Tao Wang, Feber, Andrew, Rakyan, Vardhman, Peggs, Karl S., and Beck, Stephan
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GRAFT versus host disease ,CELL transplantation ,DNA methylation ,HEMATOPOIETIC stem cell transplantation ,MACHINE learning ,CD30 antigen ,CREATININE - Abstract
Allogeneic hematopoietic cell transplantation (HCT) is used to treat many bloodbased disorders and malignancies, however it can also result in serious adverse events, such as the development of acute graft-versus-host disease (aGVHD). This study aimed to develop a donor-specific epigenetic classifier to reduce incidence of aGVHD by improving donor selection. Genome-wide DNA methylation was assessed in a discovery cohort of 288 HCT donors selected based on recipient aGVHD outcome; this cohort consisted of 144 cases with aGVHD grades III-IV and 144 controls with no aGVHD. We applied a machine learning algorithm to identify CpG sites predictive of aGVHD. Receiver operating characteristic (ROC) curve analysis of these sites resulted in a classifier with an encouraging area under the ROC curve (AUC) of 0.91. To test this classifier, we used an independent validation cohort (n = 288) selected using the same criteria as the discovery cohort. Attempts to validate the classifier failed with the AUC falling to 0.51. These results indicate that donor DNA methylation may not be a suitable predictor of aGVHD in an HCT setting involving unrelated donors, despite the initial promising results in the discovery cohort. Our work highlights the importance of independent validation of machine learning classifiers, particularly when developing classifiers intended for clinical use. [ABSTRACT FROM AUTHOR]
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- 2024
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24. An integrated assessment of the vascular plant species of the Americas
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Ulloa, Carmen Ulloa, Acevedo-Rodríguez, Pedro, Beck, Stephan, Belgrano, Manuel J., Bernal, Rodrigo, Berry, Paul E., Brako, Lois, Celis, Marcela, Davidse, Gerrit, Forzza, Rafaela C., Gradstein, S. Robbert, Hokche, Omaira, León, Blanca, León-Yánez, Susana, Magill, Robert E., Neill, David A., Nee, Michael, Raven, Peter H., Stimmel, Heather, Strong, Mark T., Villaseñor, José L., Zarucchi, James L., Zuloaga, Fernando O., and Jørgensen, Peter M.
- Published
- 2017
25. Chapter 5 Computational Analysis and Integration of MeDIP-seq Methylome Data
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Wilson, Gareth A. and Beck, Stephan
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sequencing ,biochemistry ,bic Book Industry Communication::P Mathematics & science::PS Biology, life sciences::PSB Biochemistry - Abstract
The combinatorial number of possible methylomes in biological time and space is astronomical. Consequently, the computational analysis of methylomes needs to cater for a variety of data, throughput and resolution. Here, we review recent advances in 2nd generation sequencing (2GS) with a focus on the different methods used for the analysis of MeDIP-seq data. The challenges and opportunities presented by the integration of methylation data with other genomic data types are discussed as is the potential impact of emerging 3rd generation sequencing (3GS) based technologies on methylation analysis.
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- 2016
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26. Neoantigen-directed immune escape in lung cancer evolution
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Rosenthal, Rachel, Cadieux, Elizabeth Larose, Salgado, Roberto, Bakir, Maise Al, Moore, David A., Hiley, Crispin T., Lund, Tom, Tanić, Miljana, Reading, James L., Joshi, Kroopa, Henry, Jake Y., Ghorani, Ehsan, Wilson, Gareth A., Birkbak, Nicolai J., Jamal-Hanjani, Mariam, Veeriah, Selvaraju, Szallasi, Zoltan, Loi, Sherene, Hellmann, Matthew D., Feber, Andrew, Chain, Benny, Herrero, Javier, Quezada, Sergio A., Demeulemeester, Jonas, Van Loo, Peter, Beck, Stephan, McGranahan, Nicholas, Swanton, Charles, and The TRACERx consortium
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- 2019
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27. Registered access: authorizing data access
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Dyke, Stephanie O. M., Linden, Mikael, Lappalainen, Ilkka, De Argila, Jordi Rambla, Carey, Knox, Lloyd, David, Spalding, J. Dylan, Cabili, Moran N., Kerry, Giselle, Foreman, Julia, Cutts, Tim, Shabani, Mahsa, Rodriguez, Laura L., Haeussler, Maximilian, Walsh, Brian, Jiang, Xiaoqian, Wang, Shuang, Perrett, Daniel, Boughtwood, Tiffany, Matern, Andreas, Brookes, Anthony J., Cupak, Miro, Fiume, Marc, Pandya, Ravi, Tulchinsky, Ilia, Scollen, Serena, Törnroos, Juha, Das, Samir, Evans, Alan C., Malin, Bradley A., Beck, Stephan, Brenner, Steven E., Nyrönen, Tommi, Blomberg, Niklas, Firth, Helen V., Hurles, Matthew, Philippakis, Anthony A., Rätsch, Gunnar, Brudno, Michael, Boycott, Kym M., Rehm, Heidi L., Baudis, Michael, Sherry, Stephen T., Kato, Kazuto, Knoppers, Bartha M., Baker, Dixie, and Flicek, Paul
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- 2018
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28. Identification of differentially methylated cell types in epigenome-wide association studies
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Zheng, Shijie C., Breeze, Charles E., Beck, Stephan, and Teschendorff, Andrew E.
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- 2018
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29. A histone acetylome-wide association study of Alzheimer’s disease identifies disease-associated H3K27ac differences in the entorhinal cortex
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Marzi, Sarah J., Leung, Szi Kay, Ribarska, Teodora, Hannon, Eilis, Smith, Adam R., Pishva, Ehsan, Poschmann, Jeremie, Moore, Karen, Troakes, Claire, Al-Sarraj, Safa, Beck, Stephan, Newman, Stuart, Lunnon, Katie, Schalkwyk, Leonard C., and Mill, Jonathan
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- 2018
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30. EPISCORE: cell type deconvolution of bulk tissue DNA methylomes from single-cell RNA-Seq data
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Teschendorff, Andrew E., Zhu, Tianyu, Breeze, Charles E., and Beck, Stephan
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- 2020
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31. A Distinctive New Species of Ovidia (Thymelaeaceae) from Bolivia
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Rogers, Zachary S., Antezana, Carola, Wood, J. R. I., and Beck, Stephan G.
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- 2004
32. Grazing and Environmental Change on the Tarija Altiplano, Bolivia
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Preston, David, Fairbairn, Jamie, Paniagua, Narel, Maas, Glenn, Yevara, Martha, and Beck, Stephan
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- 2003
33. RXRB Is an MHC-Encoded Susceptibility Gene Associated with Anti-Topoisomerase I Antibody-Positive Systemic Sclerosis
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Oka, Akira, Asano, Yoshihide, Hasegawa, Minoru, Fujimoto, Manabu, Ishikawa, Osamu, Kuwana, Masataka, Kawaguchi, Yasushi, Yamamoto, Toshiyuki, Takahashi, Hiroki, Goto, Daisuke, Endo, Hirahito, Jinnin, Masatoshi, Mano, Shuhei, Hosomichi, Kazuyoshi, Mabuchi, Tomotaka, Ueda, Mahoko Takahashi, Nakagawa, So, Beck, Stephan, Bahram, Seiamak, Takehara, Kazuhiko, Sato, Shinichi, and Ihn, Hironobu
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- 2017
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34. Benefits and barriers in the design of harmonized access agreements for international data sharing
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Saulnier, Katie M., Bujold, David, Dyke, Stephanie O. M., Dupras, Charles, Beck, Stephan, Bourque, Guillaume, and Joly, Yann
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- 2019
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35. DNA methylation aging clocks: challenges and recommendations
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Bell, Christopher G., Lowe, Robert, Adams, Peter D., Baccarelli, Andrea A., Beck, Stephan, Bell, Jordana T., Christensen, Brock C., Gladyshev, Vadim N., Heijmans, Bastiaan T., Horvath, Steve, Ideker, Trey, Issa, Jean-Pierre J., Kelsey, Karl T., Marioni, Riccardo E., Reik, Wolf, Relton, Caroline L., Schalkwyk, Leonard C., Teschendorff, Andrew E., Wagner, Wolfgang, Zhang, Kang, and Rakyan, Vardhman K.
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- 2019
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36. Making multi-omics data accessible to researchers
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Conesa, Ana and Beck, Stephan
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- 2019
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37. The Personal Genome Project-UK, an open access resource of human multi-omics data
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Chervova, Olga, Conde, Lucia, Guerra-Assunção, José Afonso, Moghul, Ismail, Webster, Amy P., Berner, Alison, Larose Cadieux, Elizabeth, Tian, Yuan, Voloshin, Vitaly, Jesus, Tiago F., Hamoudi, Rifat, Herrero, Javier, and Beck, Stephan
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- 2019
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38. Open access-enabled evaluation of epigenetic age acceleration in colorectal cancer and development of a classifier with diagnostic potential.
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Widayati, Tyas Arum, Schneider, Jadesada, Panteleeva, Kseniia, Chernysheva, Elizabeth, Hrbkova, Natalie, Beck, Stephan, Voloshin, Vitaly, and Chervova, Olga
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COLORECTAL cancer ,CARCINOGENESIS ,EPIGENETICS ,TRAINING of scientists ,AGE ,ADENOMATOUS polyps - Abstract
Aberrant DNA methylation (DNAm) is known to be associated with the aetiology of cancer, including colorectal cancer (CRC). In the past, the availability of open access data has been the main driver of innovative method development and research training. However, this is increasingly being eroded by the move to controlled access, particularly of medical data, including cancer DNAm data. To rejuvenate this valuable tradition, we leveraged DNAm data from 1,845 samples (535 CRC tumours, 522 normal colon tissues adjacent to tumours, 72 colorectal adenomas, and 716 normal colon tissues from healthy individuals) from 14 open access studies deposited in NCBI GEO and ArrayExpress. We calculated each sample's epigenetic age (EA) using eleven epigenetic clock models and derived the corresponding epigenetic age acceleration (EAA). For EA, we observed that most first- and second-generation epigenetic clocks reflect the chronological age in normal tissues adjacent to tumours and healthy individuals [e.g., Horvath (r = 0.77 and 0.79), Zhang elastic net (EN) (r = 0.70 and 0.73)] unlike the epigenetic mitotic clocks (EpiTOC, HypoClock, MiAge) (r < 0.3). For EAA, we used PhenoAge, Wu, and the above mitotic clocks and found them to have distinct distributions in different tissue types, particularly between normal colon tissues adjacent to tumours and cancerous tumours, as well as between normal colon tissues adjacent to tumours and normal colon tissue from healthy individuals. Finally, we harnessed these associations to develop a classifier using elastic net regression (with lasso and ridge regularisations) that predicts CRC diagnosis based on a patient's sex and EAAs calculated from histologically normal controls (i.e., normal colon tissues adjacent to tumours and normal colon tissue from healthy individuals). The classifier demonstrated good diagnostic potential with ROC-AUC = 0.886, which suggests that an EAA-based classifier trained on relevant data could become a tool to support diagnostic/prognostic decisions in CRC for clinical professionals. Our study also reemphasises the importance of open access clinical data for method development and training of young scientists. Obtaining the required approvals for controlled access data would not have been possible in the timeframe of this study. [ABSTRACT FROM AUTHOR]
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- 2023
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39. Plasticity in the Organization and Sequences of Human KIR/ILT Gene Families
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Wilson, Michael J., Torkar, Michaela, Haude, Anja, Milne, Sarah, Jones, Tania, Sheer, Denise, Beck, Stephan, and Trowsdale, John
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- 2000
40. Body composition and lung cancer-associated cachexia in TRACERx
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Al-Sawaf, Othman, Weiss, Jakob, Skrzypski, Marcin, Lam, Jie Min, Karasaki, Takahiro, Zambrana, Francisco, Kidd, Andrew C, Frankell, Alexander M, Watkins, Thomas BK, Martinez-Ruiz, Carlos, Puttick, Clare, Black, James RM, Huebner, Ariana, Al Bakir, Maise, Sokac, Mateo, Collins, Susie, Veeriah, Selvaraju, Magno, Neil, Naceur-Lombardelli, Cristina, Prymas, Paulina, Toncheva, Antonia, Ward, Sophia, Jayanth, Nick, Salgado, Roberto, Bridge, Christopher P, Christiani, David C, Mak, Raymond H, Bay, Camden, Rosenthal, Michael, Sattar, Naveed, Welsh, Paul, Liu, Ying, Perrimon, Norbert, Popuri, Karteek, Beg, Mirza Faisal, McGranahan, Nicholas, Hackshaw, Allan, Breen, Danna M, O'Rahilly, Stephen, Birkbak, Nicolai J, Aerts, Hugo JWL, Jamal-Hanjani, Mariam, Swanton, Charles, Lester, Jason F, Bajaj, Amrita, Nakas, Apostolos, Sodha-Ramdeen, Azmina, Ang, Keng, Tufail, Mohamad, Chowdhry, Mohammed Fiyaz, Scotland, Molly, Boyles, Rebecca, Rathinam, Sridhar, Wilson, Claire, Marrone, Domenic, Dulloo, Sean, Fennell, Dean A, Matharu, Gurdeep, Shaw, Jacqui A, Riley, Joan, Primrose, Lindsay, Boleti, Ekaterini, Cheyne, Heather, Khalil, Mohammed, Richardson, Shirley, Cruickshank, Tracey, Price, Gillian, Kerr, Keith M, Benafif, Sarah, Gilbert, Kayleigh, Naidu, Babu, Patel, Akshay J, Osman, Aya, Lacson, Christer, Langman, Gerald, Shackleford, Helen, Djearaman, Madava, Kadiri, Salma, Middleton, Gary, Leek, Angela, Hodgkinson, Jack Davies, Totten, Nicola, Montero, Angeles, Smith, Elaine, Fontaine, Eustace, Granato, Felice, Doran, Helen, Novasio, Juliette, Rammohan, Kendadai, Joseph, Leena, Bishop, Paul, Shah, Rajesh, Moss, Stuart, Joshi, Vijay, Crosbie, Philip, Gomes, Fabio, Brown, Kate, Carter, Mathew, Chaturvedi, Anshuman, Priest, Lynsey, Oliveira, Pedro, Lindsay, Colin R, Blackhall, Fiona H, Krebs, Matthew G, Summers, Yvonne, Clipson, Alexandra, Tugwood, Jonathan, Kerr, Alastair, Rothwell, Dominic G, Kilgour, Elaine, Dive, Caroline, Schwarz, Roland F, Kaufmann, Tom L, Wilson, Gareth A, Rosenthal, Rachel, Van Loo, Peter, Szallasi, Zoltan, Kisistok, Judit, Diossy, Miklos, Demeulemeester, Jonas, Bunkum, Abigail, Stewart, Aengus, Magness, Alastair, Rowan, Andrew, Karamani, Angeliki, Chain, Benny, Campbell, Brittany B, Castignani, Carla, Bailey, Chris, Abbosh, Christopher, Weeden, Clare E, Lee, Claudia, Richard, Corentin, Hiley, Crispin T, Moore, David A, Pearce, David R, Karagianni, Despoina, Biswas, Dhruva, Levi, Dina, Hoxha, Elena, Cadieux, Elizabeth Larose, Lim, Emilia L, Colliver, Emma, Nye, Emma, Gronroos, Eva, Galvez-Cancino, Felip, Athanasopoulou, Foteini, Gimeno-Valiente, Francisco, Kassiotis, George, Stavrou, Georgia, Mastrokalos, Gerasimos, Zhai, Haoran, Lowe, Helen L, Matos, Ignacio Garcia, Goldman, Jacki, Reading, James L, Herrero, Javier, Rane, Jayant K, Nicod, Jerome, Hartley, John A, Peggs, Karl S, Enfield, Katey SS, Selvaraju, Kayalvizhi, Thol, Kerstin, Litchfield, Kevin, Ng, Kevin W, Chen, Kezhong, Dijkstra, Krijn, Grigoriadis, Kristiana, Thakkar, Krupa, Ensell, Leah, Shah, Mansi, Duran, Marcos Vasquez, Litovchenko, Maria, Sunderland, Mariana Werner, Hill, Mark S, Dietzen, Michelle, Leung, Michelle, Escudero, Mickael, Angelova, Mihaela, Tanic, Miljana, Sivakumar, Monica, Kanu, Nnennaya, Chervova, Olga, Lucas, Olivia, Pich, Oriol, Hobson, Philip, Pawlik, Piotr, Stone, Richard Kevin, Bentham, Robert, Hynds, Robert E, Vendramin, Roberto, Saghafinia, Sadegh, Lopez, Saioa, Gamble, Samuel, Ung, Seng Kuong Anakin, Quezada, Sergio A, Vanloo, Sharon, Zaccaria, Simone, Hessey, Sonya, Boeing, Stefan, Beck, Stephan, Bola, Supreet Kaur, Denner, Tamara, Marafioti, Teresa, Mourikis, Thanos P, Spanswick, Victoria, Barbe, Vittorio, Lu, Wei-Ting, Hill, William, Liu, Wing Kin, Wu, Yin, Naito, Yutaka, Ramsden, Zoe, Veiga, Catarina, Royle, Gary, Collins-Fekete, Charles-Antoine, Fraioli, Francesco, Ashford, Paul, Clark, Tristan, Forster, Martin D, Lee, Siow Ming, Borg, Elaine, Falzon, Mary, Papadatos-Pastos, Dionysis, Wilson, James, Ahmad, Tanya, Procter, Alexander James, Ahmed, Asia, Taylor, Magali N, Nair, Arjun, Lawrence, David, Patrini, Davide, Navani, Neal, Thakrar, Ricky M, Janes, Sam M, Hoogenboom, Emilie Martinoni, Monk, Fleur, Holding, James W, Choudhary, Junaid, Bhakhri, Kunal, Scarci, Marco, Hayward, Martin, Panagiotopoulos, Nikolaos, Gorman, Pat, Khiroya, Reena, Stephens, Robert CM, Wong, Yien Ning Sophia, Bandula, Steve, Sharp, Abigail, Smith, Sean, Gower, Nicole, Dhanda, Harjot Kaur, Chan, Kitty, Pilotti, Camilla, Leslie, Rachel, Grapa, Anca, Zhang, Hanyun, AbdulJabbar, Khalid, Pan, Xiaoxi, Yuan, Yinyin, Chuter, David, MacKenzie, Mairead, Chee, Serena, Alzetani, Aiman, Cave, Judith, Scarlett, Lydia, Richards, Jennifer, Ingram, Papawadee, Austin, Silvia, Lim, Eric, De Sousa, Paulo, Jordan, Simon, Rice, Alexandra, Raubenheimer, Hilgardt, Bhayani, Harshil, Ambrose, Lyn, Devaraj, Anand, Chavan, Hema, Begum, Sofina, Buderi, Silviu, Kaniu, Daniel, Malima, Mpho, Booth, Sarah, Nicholson, Andrew G, Fernandes, Nadia, Shah, Pratibha, Proli, Chiara, Hewish, Madeleine, Danson, Sarah, Shackcloth, Michael J, Robinson, Lily, Russell, Peter, Blyth, Kevin G, Dick, Craig, Le Quesne, John, Kirk, Alan, Asif, Mo, Bilancia, Rocco, Kostoulas, Nikos, and Thomas, Mathew
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Male ,Proteomics ,Cachexia ,Lung Neoplasms ,Antigens, Neoplasm ,Carcinoma, Non-Small-Cell Lung ,Body Weight ,Body Composition ,Humans ,Neoplasm Recurrence, Local ,Muscle, Skeletal ,Neoplasm Proteins - Abstract
Cancer-associated cachexia (CAC) is a major contributor to morbidity and mortality in individuals with non-small cell lung cancer. Key features of CAC include alterations in body composition and body weight. Here, we explore the association between body composition and body weight with survival and delineate potential biological processes and mediators that contribute to the development of CAC. Computed tomography-based body composition analysis of 651 individuals in the TRACERx (TRAcking non-small cell lung Cancer Evolution through therapy (Rx)) study suggested that individuals in the bottom 20th percentile of the distribution of skeletal muscle or adipose tissue area at the time of lung cancer diagnosis, had significantly shorter lung cancer-specific survival and overall survival. This finding was validated in 420 individuals in the independent Boston Lung Cancer Study. Individuals classified as having developed CAC according to one or more features at relapse encompassing loss of adipose or muscle tissue, or body mass index-adjusted weight loss were found to have distinct tumor genomic and transcriptomic profiles compared with individuals who did not develop such features. Primary non-small cell lung cancers from individuals who developed CAC were characterized by enrichment of inflammatory signaling and epithelial-mesenchymal transitional pathways, and differentially expressed genes upregulated in these tumors included cancer-testis antigen MAGEA6 and matrix metalloproteinases, such as ADAMTS3. In an exploratory proteomic analysis of circulating putative mediators of cachexia performed in a subset of 110 individuals from TRACERx, a significant association between circulating GDF15 and loss of body weight, skeletal muscle and adipose tissue was identified at relapse, supporting the potential therapeutic relevance of targeting GDF15 in the management of CAC. ispartof: NATURE MEDICINE vol:29 issue:4 ispartof: location:United States status: Published online
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- 2023
41. The evolution of non-small cell lung cancer metastases in TRACERx
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Al Bakir, Maise, Huebner, Ariana, Martinez-Ruiz, Carlos, Grigoriadis, Kristiana, Watkins, Thomas BK, Pich, Oriol, Moore, David A, Veeriah, Selvaraju, Ward, Sophia, Laycock, Joanne, Johnson, Diana, Rowan, Andrew, Razaq, Maryam, Akther, Mita, Naceur-Lombardelli, Cristina, Prymas, Paulina, Toncheva, Antonia, Hessey, Sonya, Dietzen, Michelle, Colliver, Emma, Frankell, Alexander, Bunkum, Abigail, Lim, Emilia L, Karasaki, Takahiro, Abbosh, Christopher, Hiley, Crispin T, Hill, Mark S, Cook, Daniel E, Wilson, Gareth A, Salgado, Roberto, Nye, Emma, Stone, Richard Kevin, Fennell, Dean A, Price, Gillian, Kerr, Keith M, Naidu, Babu, Middleton, Gary, Summers, Yvonne, Lindsay, Colin R, Blackhall, Fiona H, Cave, Judith, Blyth, Kevin G, Nair, Arjun, Ahmed, Asia, Taylor, Magali N, Procter, Alexander James, Falzon, Mary, Lawrence, David, Navani, Neal, Thakrar, Ricky M, Janes, Sam M, Papadatos-Pastos, Dionysis, Forster, Martin D, Lee, Siow Ming, Ahmad, Tanya, Quezada, Sergio, Peggs, Karl S, Van Loo, Peter, Dive, Caroline, Hackshaw, Allan, Birkbak, Nicolai J, Zaccaria, Simone, Jamal-Hanjani, Mariam, McGranahan, Nicholas, Swanton, Charles, Lester, Jason F, Bajaj, Amrita, Nakas, Apostolos, Sodha-Ramdeen, Azmina, Ang, Keng, Tufail, Mohamad, Chowdhry, Mohammed Fiyaz, Scotland, Molly, Boyles, Rebecca, Rathinam, Sridhar, Wilson, Claire, Marrone, Domenic, Dulloo, Sean, Matharu, Gurdeep, Shaw, Jacqui A, Riley, Joan, Primrose, Lindsay, Boleti, Ekaterini, Cheyne, Heather, Khalil, Mohammed, Richardson, Shirley, Cruickshank, Tracey, Benafif, Sarah, Gilbert, Kayleigh, Patel, Akshay J, Osman, Aya, Lacson, Christer, Langman, Gerald, Shackleford, Helen, Djearaman, Madava, Kadiri, Salma, Leek, Angela, Hodgkinson, Jack Davies, Totten, Nicola, Montero, Angeles, Smith, Elaine, Fontaine, Eustace, Granato, Felice, Doran, Helen, Novasio, Juliette, Rammohan, Kendadai, Joseph, Leena, Bishop, Paul, Shah, Rajesh, Moss, Stuart, Joshi, Vijay, Crosbie, Philip, Gomes, Fabio, Brown, Kate, Carter, Mathew, Chaturvedi, Anshuman, Priest, Lynsey, Oliveira, Pedro, Krebs, Matthew G, Clipson, Alexandra, Tugwood, Jonathan, Kerr, Alastair, Rothwell, Dominic G, Kilgour, Elaine, Aerts, Hugo JWL, Schwarz, Roland F, Kaufmann, Tom L, Rosenthal, Rachel, Szallasi, Zoltan, Kisistok, Judit, Sokac, Mateo, Diossy, Miklos, Demeulemeester, Jonas, Stewart, Aengus, Magness, Alastair, Karamani, Angeliki, Chain, Benny, Campbell, Brittany B, Castignani, Carla, Bailey, Chris, Puttick, Clare, Weeden, Clare E, Lee, Claudia, Richard, Corentin, Pearce, David R, Karagianni, Despoina, Biswas, Dhruva, Levi, Dina, Hoxha, Elena, Larose Cadieux, Elizabeth, Gronroos, Eva, Galvez-Cancino, Felip, Athanasopoulou, Foteini, Gimeno-Valiente, Francisco, Kassiotis, George, Stavrou, Georgia, Mastrokalos, Gerasimos, Zhai, Haoran, Lowe, Helen L, Matos, Ignacio, Goldman, Jacki, Reading, James L, Black, James RM, Herrero, Javier, Rane, Jayant K, Nicod, Jerome, Lam, Jie Min, Hartley, John A, Enfield, Katey SS, Selvaraju, Kayalvizhi, Thol, Kerstin, Litchfield, Kevin, Ng, Kevin W, Chen, Kezhong, Dijkstra, Krijn, Thakkar, Krupa, Ensell, Leah, Shah, Mansi, Vasquez, Marcos, Litovchenko, Maria, Werner Sunderland, Mariana, Leung, Michelle, Escudero, Mickael, Angelova, Mihaela, Tanic, Miljana, Sivakumar, Monica, Kanu, Nnennaya, Chervova, Olga, Lucas, Olivia, Al-Sawaf, Othman, Hobson, Philip, Pawlik, Piotr, Bentham, Robert, Hynds, Robert E, Vendramin, Roberto, Saghafinia, Sadegh, Lopez, Saioa, Gamble, Samuel, Ung, Seng Kuong Anakin, Vanloo, Sharon, Boeing, Stefan, Beck, Stephan, Bola, Supreet Kaur, Denner, Tamara, Marafioti, Teresa, Mourikis, Thanos P, Spanswick, Victoria, Barbe, Vittorio, Lu, Wei-Ting, Hill, William, Liu, Wing Kin, Wu, Yin, Naito, Yutaka, Ramsden, Zoe, Veiga, Catarina, Royle, Gary, Collins-Fekete, Charles-Antoine, Fraioli, Francesco, Ashford, Paul, Clark, Tristan, Borg, Elaine, Wilson, James, Patrini, Davide, Martinoni Hoogenboom, Emilie, Monk, Fleur, Holding, James W, Choudhary, Junaid, Bhakhri, Kunal, Scarci, Marco, Hayward, Martin, Panagiotopoulos, Nikolaos, Gorman, Pat, Khiroya, Reena, Stephens, Robert CM, Wong, Yien Ning Sophia, Bandula, Steve, Sharp, Abigail, Smith, Sean, Gower, Nicole, Dhanda, Harjot Kaur, Chan, Kitty, Pilotti, Camilla, Leslie, Rachel, Grapa, Anca, Zhang, Hanyun, AbdulJabbar, Khalid, Pan, Xiaoxi, Yuan, Yinyin, Chuter, David, MacKenzie, Mairead, Chee, Serena, Alzetani, Aiman, Scarlett, Lydia, Richards, Jennifer, Ingram, Papawadee, Austin, Silvia, Lim, Eric, De Sousa, Paulo, Jordan, Simon, Rice, Alexandra, Raubenheimer, Hilgardt, Bhayani, Harshil, Ambrose, Lyn, Devaraj, Anand, Chavan, Hema, Begum, Sofina, Buderi, Silviu, Kaniu, Daniel, Malima, Mpho, Booth, Sarah, Nicholson, Andrew G, Fernandes, Nadia, Shah, Pratibha, Proli, Chiara, Hewish, Madeleine, Danson, Sarah, Shackcloth, Michael J, Robinson, Lily, Russell, Peter, Dick, Craig, Le Quesne, John, Kirk, Alan, Asif, Mo, Bilancia, Rocco, Kostoulas, Nikos, and Thomas, Mathew
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Clonal Evolution ,Cohort Studies ,Evolution, Molecular ,Lung Neoplasms ,Carcinoma, Non-Small-Cell Lung ,Disease Progression ,Humans ,Neoplasm Metastasis ,Neoplasm Recurrence, Local ,Clone Cells - Abstract
Metastatic disease is responsible for the majority of cancer-related deaths1. We report the longitudinal evolutionary analysis of 126 non-small cell lung cancer (NSCLC) tumours from 421 prospectively recruited patients in TRACERx who developed metastatic disease, compared with a control cohort of 144 non-metastatic tumours. In 25% of cases, metastases diverged early, before the last clonal sweep in the primary tumour, and early divergence was enriched for patients who were smokers at the time of initial diagnosis. Simulations suggested that early metastatic divergence more frequently occurred at smaller tumour diameters (less than 8 mm). Single-region primary tumour sampling resulted in 83% of late divergence cases being misclassified as early, highlighting the importance of extensive primary tumour sampling. Polyclonal dissemination, which was associated with extrathoracic disease recurrence, was found in 32% of cases. Primary lymph node disease contributed to metastatic relapse in less than 20% of cases, representing a hallmark of metastatic potential rather than a route to subsequent recurrences/disease progression. Metastasis-seeding subclones exhibited subclonal expansions within primary tumours, probably reflecting positive selection. Our findings highlight the importance of selection in metastatic clone evolution within untreated primary tumours, the distinction between monoclonal versus polyclonal seeding in dictating site of recurrence, the limitations of current radiological screening approaches for early diverging tumours and the need to develop strategies to target metastasis-seeding subclones before relapse. ispartof: NATURE vol:616 issue:7957 ispartof: location:England status: Published online
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- 2023
42. The evolution of lung cancer and impact of subclonal selection in TRACERx
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Frankell, Alexander M, Dietzen, Michelle, Al Bakir, Maise, Lim, Emilia L, Karasaki, Takahiro, Ward, Sophia, Veeriah, Selvaraju, Colliver, Emma, Huebner, Ariana, Bunkum, Abigail, Hill, Mark S, Grigoriadis, Kristiana, Moore, David A, Black, James RM, Liu, Wing Kin, Thol, Kerstin, Pich, Oriol, Watkins, Thomas BK, Naceur-Lombardelli, Cristina, Cook, Daniel E, Salgado, Roberto, Wilson, Gareth A, Bailey, Chris, Angelova, Mihaela, Bentham, Robert, Martinez-Ruiz, Carlos, Abbosh, Christopher, Nicholson, Andrew G, Le Quesne, John, Biswas, Dhruva, Rosenthal, Rachel, Puttick, Clare, Hessey, Sonya, Lee, Claudia, Prymas, Paulina, Toncheva, Antonia, Smith, Jon, Xing, Wei, Nicod, Jerome, Price, Gillian, Kerr, Keith M, Naidu, Babu, Middleton, Gary, Blyth, Kevin G, Fennell, Dean A, Forster, Martin D, Lee, Siow Ming, Falzon, Mary, Hewish, Madeleine, Shackcloth, Michael J, Lim, Eric, Benafif, Sarah, Russell, Peter, Boleti, Ekaterini, Krebs, Matthew G, Lester, Jason F, Papadatos-Pastos, Dionysis, Ahmad, Tanya, Thakrar, Ricky M, Lawrence, David, Navani, Neal, Janes, Sam M, Dive, Caroline, Blackhall, Fiona H, Summers, Yvonne, Cave, Judith, Marafioti, Teresa, Herrero, Javier, Quezada, Sergio A, Peggs, Karl S, Schwarz, Roland F, Van Loo, Peter, Miedema, Daniel M, Birkbak, Nicolai J, Hiley, Crispin T, Hackshaw, Allan, Zaccaria, Simone, Jamal-Hanjani, Mariam, McGranahan, Nicholas, Swanton, Charles, Bajaj, Amrita, Nakas, Apostolos, Sodha-Ramdeen, Azmina, Ang, Keng, Tufail, Mohamad, Chowdhry, Mohammed Fiyaz, Scotland, Molly, Boyles, Rebecca, Rathinam, Sridhar, Wilson, Claire, Marrone, Domenic, Dulloo, Sean, Matharu, Gurdeep, Shaw, Jacqui A, Riley, Joa, Primrose, Lindsay, Cheyne, Heather, Khalil, Mohammed, Richardson, Shirley, Cruickshank, Tracey, Gilbert, Kayleigh, Patel, Akshay J, Osman, Aya, Lacson, Christer, Langman, Gerald, Shackleford, Helen, Djearaman, Madava, Kadiri, Salma, Leek, Angela, Hodgkinson, Jack Davies, Totten, Nicola, Montero, Angeles, Smith, Elaine, Fontaine, Eustace, Granato, Felice, Doran, Helen, Novasio, Juliette, Rammohan, Kendadai, Joseph, Leena, Bishop, Paul, Shah, Rajesh, Moss, Stuart, Joshi, Vijay, Crosbie, Philip, Gomes, Fabio, Brown, Kate, Carter, Mathew, Chaturvedi, Anshuman, Priest, Lynsey, Oliveira, Pedro, Lindsay, Colin R, Clipson, Alexandra, Tugwood, Jonathan, Kerr, Alastair, Rothwell, Dominic G, Kilgour, Elaine, Aerts, Hugo JWL, Kaufmann, Tom L, Szallasi, Zoltan, Kisistok, Judit, Sokac, Mateo, Diossy, Miklos, Demeulemeester, Jonas, Stewart, Aengus, Magness, Alastair, Rowan, Andrew, Karamani, Angeliki, Chain, Benny, Campbell, Brittany B, Castignani, Carla, Weeden, Clare E, Richard, Corentin, Pearce, David R, Karagianni, Despoina, Levi, Dina, Hoxha, Elena, Larose Cadieux, Elizabeth, Nye, Emma, Gronroos, Eva, Galvez-Cancino, Felip, Athanasopoulou, Foteini, Gimeno-Valiente, Francisco, Kassiotis, George, Stavrou, Georgia, Mastrokalos, Gerasimos, Zhai, Haoran L, Lowe, Helen L, Matos, Ignacio, Goldman, Jacki, Reading, James L, Rane, Jayant K, Lam, Jie Min, Hartley, John A, Enfield, Katey SS, Selvaraju, Kayalvizhi, Litchfield, Kevin, Ng, Kevin W, Chen, Kezhong, Dijkstra, Krijn, Thakkar, Krupa, Ensell, Leah, Shah, Mansi, Vasquez, Marcos, Litovchenko, Maria, Werner Sunderland, Mariana, Leung, Michelle, Escudero, Mickael, Tanic, Miljana, Sivakumar, Monica, Kanu, Nnennaya, Chervova, Olga, Lucas, Olivia, Al-Sawaf, Othman, Hobson, Philip, Pawlik, Piotr, Stone, Richard Kevin, Hynds, Robert E, Vendramin, Roberto, Saghafinia, Sadegh, Lopez, Saioa, Gamble, Samuel, Ung, Seng Kuong Anakin, Vanloo, Sharon, Boeing, Stefan, Beck, Stephan, Bola, Supreet Kaur, Denner, Tamara, Mourikis, Thanos P, Spanswick, Victoria, Barbe, Vittorio, Lu, Wei-Ting, Hill, William, Wu, Yin, Naito, Yutaka, Ramsden, Zoe, Veiga, Catarina, Royle, Gary, Collins-Fekete, Charles-Antoine, Fraioli, Francesco, Ashford, Paul, Clark, Tristan, Borg, Elaine, Wilson, James, Procter, Alexander James, Ahmed, Asia, Taylor, Magali N, Nair, Arjun, Patrini, Davide, Martinoni Hoogenboom, Emilie, Monk, Fleur, Holding, James W, Choudhary, Junaid, Bhakhri, Kunal, Scarci, Marco, Hayward, Martin, Panagiotopoulos, Nikolaos, Gorman, Pat, Khiroya, Reena, Stephens, Robert CM, Wong, Yien Ning Sophia, Bandula, Steve, Sharp, Abigail, Smith, Sean, Gower, Nicole, Dhanda, Harjot Kaur, Chan, Kitty, Pilotti, Camilla, Leslie, Rachel, Grapa, Anca, Zhang, Hanyun, AbdulJabbar, Khalid, Pan, Xiaoxi, Yuan, Yinyin, Chuter, David, MacKenzie, Mairead, Chee, Serena, Alzetani, Aiman, Scarlett, Lydia, Richards, Jennifer, Ingram, Papawadee, Austin, Silvia, De Sousa, Paulo, Jordan, Simon, Rice, Alexandra, Raubenheimer, Hilgardt, Bhayani, Harshil, Ambrose, Lyn, Devaraj, Anand, Chavan, Hema, Begum, Sofina, Buderi, Silviu, Kaniu, Daniel, Malima, Mpho, Booth, Sarah, Fernandes, Nadia, Shah, Pratibha, Proli, Chiara, Danson, Sarah, Robinson, Lily, Dick, Craig, Kirk, Alan, Asif, Mo, Bilancia, Rocco, Kostoulas, Nikos, and Thomas, Mathew
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Lung Neoplasms ,Treatment Outcome ,DNA Copy Number Variations ,Mutagenesis ,Carcinoma, Non-Small-Cell Lung ,Mutation ,Smoking ,Humans ,Adenocarcinoma of Lung ,Neoplasm Recurrence, Local ,Phylogeny - Abstract
Lung cancer is the leading cause of cancer-associated mortality worldwide1. Here we analysed 1,644 tumour regions sampled at surgery or during follow-up from the first 421 patients with non-small cell lung cancer prospectively enrolled into the TRACERx study. This project aims to decipher lung cancer evolution and address the primary study endpoint: determining the relationship between intratumour heterogeneity and clinical outcome. In lung adenocarcinoma, mutations in 22 out of 40 common cancer genes were under significant subclonal selection, including classical tumour initiators such as TP53 and KRAS. We defined evolutionary dependencies between drivers, mutational processes and whole genome doubling (WGD) events. Despite patients having a history of smoking, 8% of lung adenocarcinomas lacked evidence of tobacco-induced mutagenesis. These tumours also had similar detection rates for EGFR mutations and for RET, ROS1, ALK and MET oncogenic isoforms compared with tumours in never-smokers, which suggests that they have a similar aetiology and pathogenesis. Large subclonal expansions were associated with positive subclonal selection. Patients with tumours harbouring recent subclonal expansions, on the terminus of a phylogenetic branch, had significantly shorter disease-free survival. Subclonal WGD was detected in 19% of tumours, and 10% of tumours harboured multiple subclonal WGDs in parallel. Subclonal, but not truncal, WGD was associated with shorter disease-free survival. Copy number heterogeneity was associated with extrathoracic relapse within 1 year after surgery. These data demonstrate the importance of clonal expansion, WGD and copy number instability in determining the timing and patterns of relapse in non-small cell lung cancer and provide a comprehensive clinical cancer evolutionary data resource. ispartof: NATURE vol:616 issue:7957 ispartof: location:England status: Published online
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- 2023
43. Evolutionary characterization of lung adenocarcinoma morphology in TRACERx
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Karasaki, Takahiro, Moore, David A, Veeriah, Selvaraju, Naceur-Lombardelli, Cristina, Toncheva, Antonia, Magno, Neil, Ward, Sophia, Al Bakir, Maise, Watkins, Thomas BK, Grigoriadis, Kristiana, Huebner, Ariana, Hill, Mark S, Frankell, Alexander M, Abbosh, Christopher, Puttick, Clare, Zhai, Haoran, Gimeno-Valiente, Francisco, Saghafinia, Sadegh, Kanu, Nnennaya, Dietzen, Michelle, Pich, Oriol, Lim, Emilia L, Martinez-Ruiz, Carlos, Black, James RM, Biswas, Dhruva, Campbell, Brittany B, Lee, Claudia, Colliver, Emma, Enfield, Katey SS, Hessey, Sonya, Hiley, Crispin T, Zaccaria, Simone, Litchfield, Kevin, Birkbak, Nicolai J, Cadieux, Elizabeth Larose, Demeulemeester, Jonas, Van Loo, Peter, Adusumilli, Prasad R, Tan, Kay See, Cheema, Waseem, Sanchez-Vega, Francisco, Jones, David R, Rekhtman, Natasha, Travis, William D, Hackshaw, Allan, Marafioti, Teresa, Salgado, Roberto, Le Quesne, John, Nicholson, Andrew G, McGranahan, Nicholas, Swanton, Charles, Jamal-Hanjani, Mariam, Lester, Jason F, Bajaj, Amrita, Nakas, Apostolos, Sodha-Ramdeen, Azmina, Ang, Keng, Tufail, Mohamad, Chowdhry, Mohammed Fiyaz, Scotland, Molly, Boyles, Rebecca, Rathinam, Sridhar, Wilson, Claire, Marrone, Domenic, Dulloo, Sean, Fennell, Dean A, Matharu, Gurdeep, Shaw, Jacqui A, Riley, Joan, Primrose, Lindsay, Boleti, Ekaterini, Cheyne, Heather, Khalil, Mohammed, Richardson, Shirley, Cruickshank, Tracey, Price, Gillian, Kerr, Keith M, Benafif, Sarah, Gilbert, Kayleigh, Naidu, Babu, Patel, Akshay J, Osman, Aya, Lacson, Christer, Langman, Gerald, Shackleford, Helen, Djearaman, Madava, Kadiri, Salma, Middleton, Gary, Leek, Angela, Hodgkinson, Jack Davies, Totten, Nicola, Montero, Angeles, Smith, Elaine, Fontaine, Eustace, Granato, Felice, Doran, Helen, Novasio, Juliette, Rammohan, Kendadai, Joseph, Leena, Bishop, Paul, Shah, Rajesh, Moss, Stuart, Joshi, Vijay, Crosbie, Philip, Gomes, Fabio, Brown, Kate, Carter, Mathew, Chaturvedi, Anshuman, Priest, Lynsey, Oliveira, Pedro, Lindsay, Colin R, Blackhall, Fiona H, Krebs, Matthew G, Summers, Yvonne, Clipson, Alexandra, Tugwood, Jonathan, Kerr, Alastair, Rothwell, Dominic G, Kilgour, Elaine, Dive, Caroline, Aerts, Hugo JWL, Schwarz, Roland F, Kaufmann, Tom L, Wilson, Gareth A, Rosenthal, Rachel, Szallasi, Zoltan, Kisistok, Judit, Sokac, Mateo, Diossy, Miklos, Bunkum, Abigail, Stewart, Aengus, Magness, Alastair, Rowan, Andrew, Karamani, Angeliki, Chain, Benny, Castignani, Carla, Bailey, Chris, Weeden, Clare E, Richard, Corentin, Pearce, David R, Karagianni, Despoina, Levi, Dina, Hoxha, Elena, Nye, Emma, Gronroos, Eva, Galvez-Cancino, Felip, Athanasopoulou, Foteini, Kassiotis, George, Stavrou, Georgia, Mastrokalos, Gerasimos, Lowe, Helen L, Matos, Ignacio Garcia, Goldman, Jacki, Reading, James L, Herrero, Javier, Rane, Jayant K, Nicod, Jerome, Lam, Jie Min, Hartley, John A, Peggs, Karl S, Selvaraju, Kayalvizhi, Thol, Kerstin, Ng, Kevin W, Chen, Kezhong, Dijkstra, Krijn, Thakkar, Krupa, Ensell, Leah, Shah, Mansi, Duran, Marcos Vasquez, Litovchenko, Maria, Sunderland, Mariana Werner, Leung, Michelle, Escudero, Mickael, Angelova, Mihaela, Tanic, Miljana, Sivakumar, Monica, Chervova, Olga, Lucas, Olivia, Al-Sawaf, Othman, Prymas, Paulina, Hobson, Philip, Pawlik, Piotr, Stone, Richard Kevin, Bentham, Robert, Hynds, Robert E, Vendramin, Roberto, Lopez, Saioa, Gamble, Samuel, Ung, Seng Kuong Anakin, Quezada, Sergio A, Vanloo, Sharon, Boeing, Stefan, Beck, Stephan, Bola, Supreet Kaur, Denner, Tamara, Mourikis, Thanos P, Spanswick, Victoria, Barbe, Vittorio, Lu, Wei-Ting, Hill, William, Liu, Wing Kin, Wu, Yin, Naito, Yutaka, Ramsden, Zoe, Veiga, Catarina, Royle, Gary, Collins-Fekete, Charles-Antoine, Fraioli, Francesco, Ashford, Paul, Clark, Tristan, Forster, Martin D, Lee, Siow Ming, Borg, Elaine, Falzon, Mary, Papadatos-Pastos, Dionysis, Wilson, James, Ahmad, Tanya, Procter, Alexander James, Ahmed, Asia, Taylor, Magali N, Nair, Arjun, Lawrence, David, Patrini, Davide, Navani, Neal, Thakrar, Ricky M, Janes, Sam M, Hoogenboom, Emilie Martinoni, Monk, Fleur, Holding, James W, Choudhary, Junaid, Bhakhri, Kunal, Scarci, Marco, Hayward, Martin, Panagiotopoulos, Nikolaos, Gorman, Pat, Khiroya, Reena, Stephens, Robert CM, Wong, Yien Ning Sophia, Bandula, Steve, Sharp, Abigail, Smith, Sean, Gower, Nicole, Dhanda, Harjot Kaur, Chan, Kitty, Pilotti, Camilla, Leslie, Rachel, Grapa, Anca, Zhang, Hanyun, AbdulJabbar, Khalid, Pan, Xiaoxi, Yuan, Yinyin, Chuter, David, MacKenzie, Mairead, Chee, Serena, Alzetani, Aiman, Cave, Judith, Scarlett, Lydia, Richards, Jennifer, Ingram, Papawadee, Austin, Silvia, Lim, Eric, De Sousa, Paulo, Jordan, Simon, Rice, Alexandra, Raubenheimer, Hilgardt, Bhayani, Harshil, Ambrose, Lyn, Devaraj, Anand, Chavan, Hema, Begum, Sofina, Buderi, Silviu, Kaniu, Daniel, Malima, Mpho, Booth, Sarah, Fernandes, Nadia, Shah, Pratibha, Proli, Chiara, Hewish, Madeleine, Danson, Sarah, Shackcloth, Michael J, Robinson, Lily, Russell, Peter, Blyth, Kevin G, Dick, Craig, Kirk, Alan, Asif, Mo, Bilancia, Rocco, Kostoulas, Nikos, and Thomas, Mathew
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TRACERx Consortium - Abstract
Lung adenocarcinomas (LUADs) display a broad histological spectrum from low-grade lepidic tumors through to mid-grade acinar and papillary and high-grade solid, cribriform and micropapillary tumors. How morphology reflects tumor evolution and disease progression is poorly understood. Whole-exome sequencing data generated from 805 primary tumor regions and 121 paired metastatic samples across 248 LUADs from the TRACERx 421 cohort, together with RNA-sequencing data from 463 primary tumor regions, were integrated with detailed whole-tumor and regional histopathological analysis. Tumors with predominantly high-grade patterns showed increased chromosomal complexity, with higher burden of loss of heterozygosity and subclonal somatic copy number alterations. Individual regions in predominantly high-grade pattern tumors exhibited higher proliferation and lower clonal diversity, potentially reflecting large recent subclonal expansions. Co-occurrence of truncal loss of chromosomes 3p and 3q was enriched in predominantly low-/mid-grade tumors, while purely undifferentiated solid-pattern tumors had a higher frequency of truncal arm or focal 3q gains and SMARCA4 gene alterations compared with mixed-pattern tumors with a solid component, suggesting distinct evolutionary trajectories. Clonal evolution analysis revealed that tumors tend to evolve toward higher-grade patterns. The presence of micropapillary pattern and 'tumor spread through air spaces' were associated with intrathoracic recurrence, in contrast to the presence of solid/cribriform patterns, necrosis and preoperative circulating tumor DNA detection, which were associated with extra-thoracic recurrence. These data provide insights into the relationship between LUAD morphology, the underlying evolutionary genomic landscape, and clinical and anatomical relapse risk. ispartof: NATURE MEDICINE vol:29 issue:4 ispartof: location:United States status: Published online
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- 2023
44. Epigenetic and Transcriptional Variability Shape Phenotypic Plasticity
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Ecker, Simone, Pancaldi, Vera, Valencia, Alfonso, Beck, Stephan, and Paul, Dirk S.
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- 2018
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45. Systematic evaluation of library preparation methods and sequencing platforms for high-throughput whole genome bisulfite sequencing
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Zhou, Li, Ng, Hong Kiat, Drautz-Moses, Daniela I., Schuster, Stephan C., Beck, Stephan, Kim, Changhoon, Chambers, John Campbell, and Loh, Marie
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- 2019
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46. Neuronal methylome reveals CREB-associated neuro-axonal impairment in multiple sclerosis
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Kular, Lara, Needhamsen, Maria, Adzemovic, Milena Z., Kramarova, Tatiana, Gomez-Cabrero, David, Ewing, Ewoud, Piket, Eliane, Tegnér, Jesper, Beck, Stephan, Piehl, Fredrik, Brundin, Lou, and Jagodic, Maja
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- 2019
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47. Points-to-consider on the return of results in epigenetic research
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Dyke, Stephanie O. M., Saulnier, Katie M., Dupras, Charles, Webster, Amy P., Maschke, Karen, Rothstein, Mark, Siebert, Reiner, Walter, Jörn, Beck, Stephan, Pastinen, Tomi, and Joly, Yann
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- 2019
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48. Correction to: Functional variation in allelic methylomes underscores a strong genetic contribution and reveals novel epigenetic alterations in the human epigenome
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Cheung, Warren A., Shao, Xiaojian, Morin, Andréanne, Siroux, Valérie, Kwan, Tony, Ge, Bing, Aïssi, Dylan, Chen, Lu, Vasquez, Louella, Allum, Fiona, Guénard, Frédéric, Bouzigon, Emmanuelle, Simon, Marie-Michelle, Boulier, Elodie, Redensek, Adriana, Watt, Stephen, Datta, Avik, Clarke, Laura, Flicek, Paul, Mead, Daniel, Paul, Dirk S., Beck, Stephan, Bourque, Guillaume, Lathrop, Mark, Tchernof, André, Vohl, Marie-Claude, Demenais, Florence, Pin, Isabelle, Downes, Kate, Stunnenberg, Hendrick G., Soranzo, Nicole, Pastinen, Tomi, and Grundberg, Elin
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- 2019
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49. Subclassification of epithelioid sarcoma with potential therapeutic impact.
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Haefliger, Simon, Chervova, Olga, Davies, Christopher, Nottley, Steven, Hargreaves, Steven, Sumathi, Vaiyapuri P, Amary, Fernanda, Tirabosco, Roberto, Pillay, Nischalan, Beck, Stephan, Flanagan, Adrienne M, and Lyskjær, Iben
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PERIPHERAL nerve tumors ,SARCOMA ,IMMUNE checkpoint inhibitors ,GENE expression ,PERIPHERAL nervous system - Abstract
Epithelioid sarcoma is a rare and aggressive mesenchymal tumour, the genetic hallmark of which is the loss of expression of SMARCB1, a key member of the SWItch/Sucrose Non‐Fermentable (SWI/SNF) chromatin remodelling complex. Hampered by its rarity, epithelioid sarcoma has received little research attention and therapeutic options for this disease remain limited. SMARCB1‐deficient tumours also include malignant rhabdoid tumour, atypical teratoid and rhabdoid tumour, epithelioid malignant peripheral nerve sheath tumour, and poorly differentiated chordoma. Histologically, it can be challenging to distinguish epithelioid sarcoma from malignant rhabdoid tumour and other SMARCB1‐deficient tumours, whereas methylation profiling shows that they represent distinct entities and facilitates their classification. Methylation studies on SMARCB1‐deficient tumours, although not including epithelioid sarcomas, reported methylation subgroups which resulted in new clinical stratification and therapeutic approaches. In addition, emerging evidence indicates that immunotherapy, including immune checkpoint inhibitors, represents a promising therapeutic strategy for SMARCB1‐deficient tumours. Here, we show that some epithelioid sarcomas share methylation patterns of malignant rhabdoid tumours indicating that this could help to distinguish these entities and guide treatment. Using gene expression data, we also showed that the immune environment of epithelioid sarcoma is characterised by a predominance of CD8+ lymphocytes and M2 macrophages. These findings have potential implications for the management of patients with epithelioid sarcoma. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]
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- 2023
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50. Strategies of diaspore dispersal investment in Compositae: the case of the Andean highlands.
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Tovar, Carolina, Hudson, Lucia, Cuesta, Francisco, Meneses, Rosa Isela, Muriel, Priscilla, Hidalgo, Oriane, Palazzesi, Luis, Ballesteros, Carlos Suarez, Hunt, Eleanor Hammond, Diazgranados, Mauricio, Hind, D J Nicholas, Forest, Félix, Halloy, Stephan, Aguirre, Nikolay, Baker, William J, Beck, Stephan, Carilla, Julieta, Eguiguren, Paúl, Françoso, Elaine, and Gámez, Luis E
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FRAGMENTED landscapes ,BIOTIC communities ,SPECIES distribution ,UPLANDS ,MOUNTAIN ecology - Abstract
Background and Aims Understanding diaspore morphology and how much a species invests on dispersal appendages is key for improving our knowledge of dispersal in fragmented habitats. We investigate diaspore morphological traits in high-Andean Compositae and their main abiotic and biotic drivers and test whether they play a role in species distribution patterns across the naturally fragmented high-Andean grasslands. Methods We collected diaspore trait data for 125 Compositae species across 47 tropical high-Andean summits, focusing on achene length and pappus-to-achene length ratio, with the latter as a proxy of dispersal investment. We analysed the role of abiotic (temperature, elevation and latitude) and biotic factors (phylogenetic signal and differences between tribes) on diaspore traits and whether they are related to distribution patterns across the Andes, using phylogenomics, distribution modelling and community ecology analyses. Key Results Seventy-five percent of the studied species show small achenes (length <3.3 mm) and 67% have high dispersal investment (pappus length at least two times the achene length). Dispersal investment increases with elevation, possibly to compensate for lower air density, and achene length increases towards the equator, where non-seasonal climate prevails. Diaspore traits show significant phylogenetic signal, and higher dispersal investment is observed in Gnaphalieae, Astereae and Senecioneae, which together represent 72% of our species. High-Andean-restricted species found across the tropical Andes have, on average, the pappus four times longer than the achene, a significantly higher dispersal investment than species present only in the northern Andes or only in the central Andes. Conclusions Small achenes and high diaspore dispersal investment dominate among high-Andean Compositae, traits typical of mostly three tribes of African origin; but traits are also correlated with the environmental gradients within the high-Andean grasslands. Our results also suggest that diaspore dispersal investment is likely to shape species distribution patterns in naturally fragmented habitats. [ABSTRACT FROM AUTHOR]
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- 2023
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