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2. The potential of epigenetic therapy to target the 3D epigenome in endocrine-resistant breast cancer

Author

Achinger-Kawecka, Joanna, Stirzaker, Clare, Portman, Neil, Campbell, Elyssa, Chia, Kee-Ming, Du, Qian, Laven-Law, Geraldine, Nair, Shalima S., Yong, Aliza, Wilkinson, Ashleigh, Clifton, Samuel, Milioli, Heloisa H., Alexandrou, Sarah, Caldon, C. Elizabeth, Song, Jenny, Khoury, Amanda, Meyer, Braydon, Chen, Wenhan, Pidsley, Ruth, Qu, Wenjia, Gee, Julia M. W., Schmitt, Anthony, Wong, Emily S., Hickey, Theresa E., Lim, Elgene, and Clark, Susan J.

Published
2024
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5. Self-assembly of Dawson-type H6P2W18O62@[Cu6O(TZI)3(H2O)6]4 for high-performance aerobic oxidation desulfurization of fuel.

Author

Qu, Wenjia, Wei, Pengpeng, Li, Jingfang, Liang, Liye, Ma, Liqiang, and Li, Guangming

Subjects
*HETEROGENEOUS catalysts, *AMMONIUM chloride, *FREE radicals, *WASTE recycling, *CRYSTAL structure
Abstract

Because global sulfur emission has escalated, the development of high-efficiency deep desulfurization techniques has become imperative. Herein, to design a high-activity heterogeneous catalyst for the aerobic oxidation desulfurization (AODS) of fuel, Dawson-type polyoxometalate (H6P2W18O62 abbreviated as D-P2W18), characterized by its high activity and strong oxidative capacity, was applied to react with CuCl2·2H2O and H3TZI via a one-pot hydrothermal method. Consequently, blue crystalline H6P2W18O62@[Cu6O(TZI)3(H2O)6]4 (abbreviated as D-P2W18@rht-MOF-1; rht-MOF-1 = [Cu6O(TZI)3(H2O)6]4·nH2O) was afforded. X-ray diffraction analysis indicated that D-P2W18 was successfully encapsulated in two different cages of rht-MOF-1, which is distinct from the crystal structure of Keggin-type POMs@rht-MOF-1. It represents the first crystal structure of Dawson-type POMs@rht-MOF-1. When D-P2W18@rht-MOF-1 was employed as a catalyst for AODS under ambient oxygen pressure with the assistance of surfactant dioctadecyl dimethyl ammonium chloride (DODMAC), it demonstrated remarkable catalytic capability and recyclability for both model fuel and commercial diesel. Further, the AODS reaction mechanism, identified as a free radical oxidation–reduction process, was verified by way of radical quenching experiments, EPR and XPS analysis. This approach offers a feasible route for the synthesis of new Dawson-type POMs@MOFs of heterogeneous catalysts for highly active AODS of fuel. [ABSTRACT FROM AUTHOR]

Published
2024
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8. Quantitative comparison of DNA methylation assays for biomarker development and clinical applications

Author

Bock, Christoph, Halbritter, Florian, Carmona, Francisco J, Tierling, Sascha, Datlinger, Paul, Assenov, Yassen, Berdasco, Maria, Bergmann, Anke K, Booher, Keith, Busato, Florence, Campan, Mihaela, Dahl, Christina, Dahmcke, Christina M, Diep, Dinh, Fernandez, Agustin F, Gerhauser, Clarissa, Haake, Andrea, Heilmann, Katharina, Holcomb, Thomas, Hussmann, Dianna, Ito, Mitsuteru, Klaever, Ruth, Kreutz, Martin, Kulis, Marta, Lopez, Virginia, Nair, Shalima S, Paul, Dirk S, Plongthongkum, Nongluk, Qu, Wenjia, Queiros, Ana C, Reinicke, Frank, Sauter, Guido, Schlomm, Thorsten, Statham, Aaron, Stirzaker, Clare, Strogantsev, Ruslan, Urdinguio, Rocio G, Walter, Kimberly, Weichenhan, Dieter, Weisenberger, Daniel J, Beck, Stephan, Clark, Susan J, Esteller, Manel, Ferguson-Smith, Anne C, Fraga, Mario F, Guldberg, Per, Hansen, Lise Lotte, Laird, Peter W, Martin-Subero, Jose I, Nygren, Anders OH, Peist, Ralf, Plass, Christoph, Shames, David S, Siebert, Reiner, Sun, Xueguang, Tost, Jorg, Walter, Joern, and Zhang, Kun

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Clinical Sciences, Genetics, Algorithms, DNA, DNA Methylation, DNA Modification Methylases, Genetic Markers, High-Throughput Nucleotide Sequencing, High-Throughput Screening Assays, Promoter Regions, Genetic, Reproducibility of Results, Sensitivity and Specificity, BLUEPRINT consortium
Abstract

DNA methylation patterns are altered in numerous diseases and often correlate with clinically relevant information such as disease subtypes, prognosis and drug response. With suitable assays and after validation in large cohorts, such associations can be exploited for clinical diagnostics and personalized treatment decisions. Here we describe the results of a community-wide benchmarking study comparing the performance of all widely used methods for DNA methylation analysis that are compatible with routine clinical use. We shipped 32 reference samples to 18 laboratories in seven different countries. Researchers in those laboratories collectively contributed 21 locus-specific assays for an average of 27 predefined genomic regions, as well as six global assays. We evaluated assay sensitivity on low-input samples and assessed the assays' ability to discriminate between cell types. Good agreement was observed across all tested methods, with amplicon bisulfite sequencing and bisulfite pyrosequencing showing the best all-round performance. Our technology comparison can inform the selection, optimization and use of DNA methylation assays in large-scale validation studies, biomarker development and clinical diagnostics.

Published
2016

11. Epigenetic reprogramming at estrogen-receptor binding sites alters 3D chromatin landscape in endocrine-resistant breast cancer

Author

Achinger-Kawecka, Joanna, Valdes-Mora, Fatima, Luu, Phuc-Loi, Giles, Katherine A., Caldon, C. Elizabeth, Qu, Wenjia, Nair, Shalima, Soto, Sebastian, Locke, Warwick J., Yeo-Teh, Nicole S., Gould, Cathryn M., Du, Qian, Smith, Grady C., Ramos, Irene R., Fernandez, Kristine F., Hoon, Dave S., Gee, Julia M. W., Stirzaker, Clare, and Clark, Susan J.

Published
2020
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13. Supplementary Figure 4 from Epigenetic Deregulation Across Chromosome 2q14.2 Differentiates Normal from Prostate Cancer and Provides a Regional Panel of Novel DNA Methylation Cancer Biomarkers

Author

Devaney, James, primary, Stirzaker, Clare, primary, Qu, Wenjia, primary, Song, Jenny Z., primary, Statham, Aaron L., primary, Patterson, Kate I., primary, Horvath, Lisa G., primary, Tabor, Bruce, primary, Coolen, Marcel W., primary, Hulf, Toby, primary, Kench, James G., primary, Henshall, Susan M., primary, Pe Benito, Ruth, primary, Haynes, Anne-Maree, primary, Mayor, Regina, primary, Peinado, Miguel A., primary, Sutherland, Robert L., primary, and Clark, Susan J., primary

Published
2023
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14. Supplementary Figure 1 from Epigenetic Deregulation Across Chromosome 2q14.2 Differentiates Normal from Prostate Cancer and Provides a Regional Panel of Novel DNA Methylation Cancer Biomarkers

Author

Devaney, James, primary, Stirzaker, Clare, primary, Qu, Wenjia, primary, Song, Jenny Z., primary, Statham, Aaron L., primary, Patterson, Kate I., primary, Horvath, Lisa G., primary, Tabor, Bruce, primary, Coolen, Marcel W., primary, Hulf, Toby, primary, Kench, James G., primary, Henshall, Susan M., primary, Pe Benito, Ruth, primary, Haynes, Anne-Maree, primary, Mayor, Regina, primary, Peinado, Miguel A., primary, Sutherland, Robert L., primary, and Clark, Susan J., primary

Published
2023
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15. Supplementary Tables 1-3 from Epigenetic Deregulation Across Chromosome 2q14.2 Differentiates Normal from Prostate Cancer and Provides a Regional Panel of Novel DNA Methylation Cancer Biomarkers

Author

Devaney, James, primary, Stirzaker, Clare, primary, Qu, Wenjia, primary, Song, Jenny Z., primary, Statham, Aaron L., primary, Patterson, Kate I., primary, Horvath, Lisa G., primary, Tabor, Bruce, primary, Coolen, Marcel W., primary, Hulf, Toby, primary, Kench, James G., primary, Henshall, Susan M., primary, Pe Benito, Ruth, primary, Haynes, Anne-Maree, primary, Mayor, Regina, primary, Peinado, Miguel A., primary, Sutherland, Robert L., primary, and Clark, Susan J., primary

Published
2023
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16. Data from Epigenetic Deregulation Across Chromosome 2q14.2 Differentiates Normal from Prostate Cancer and Provides a Regional Panel of Novel DNA Methylation Cancer Biomarkers

Author

Devaney, James, primary, Stirzaker, Clare, primary, Qu, Wenjia, primary, Song, Jenny Z., primary, Statham, Aaron L., primary, Patterson, Kate I., primary, Horvath, Lisa G., primary, Tabor, Bruce, primary, Coolen, Marcel W., primary, Hulf, Toby, primary, Kench, James G., primary, Henshall, Susan M., primary, Pe Benito, Ruth, primary, Haynes, Anne-Maree, primary, Mayor, Regina, primary, Peinado, Miguel A., primary, Sutherland, Robert L., primary, and Clark, Susan J., primary

Published
2023
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17. Supplementary Table and Figure Legends from Epigenetic Deregulation Across Chromosome 2q14.2 Differentiates Normal from Prostate Cancer and Provides a Regional Panel of Novel DNA Methylation Cancer Biomarkers

Author

Devaney, James, primary, Stirzaker, Clare, primary, Qu, Wenjia, primary, Song, Jenny Z., primary, Statham, Aaron L., primary, Patterson, Kate I., primary, Horvath, Lisa G., primary, Tabor, Bruce, primary, Coolen, Marcel W., primary, Hulf, Toby, primary, Kench, James G., primary, Henshall, Susan M., primary, Pe Benito, Ruth, primary, Haynes, Anne-Maree, primary, Mayor, Regina, primary, Peinado, Miguel A., primary, Sutherland, Robert L., primary, and Clark, Susan J., primary

Published
2023
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18. Supplementary Figure 3 from Epigenetic Deregulation Across Chromosome 2q14.2 Differentiates Normal from Prostate Cancer and Provides a Regional Panel of Novel DNA Methylation Cancer Biomarkers

Author

Devaney, James, primary, Stirzaker, Clare, primary, Qu, Wenjia, primary, Song, Jenny Z., primary, Statham, Aaron L., primary, Patterson, Kate I., primary, Horvath, Lisa G., primary, Tabor, Bruce, primary, Coolen, Marcel W., primary, Hulf, Toby, primary, Kench, James G., primary, Henshall, Susan M., primary, Pe Benito, Ruth, primary, Haynes, Anne-Maree, primary, Mayor, Regina, primary, Peinado, Miguel A., primary, Sutherland, Robert L., primary, and Clark, Susan J., primary

Published
2023
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19. Supplementary Figure 2 from Epigenetic Deregulation Across Chromosome 2q14.2 Differentiates Normal from Prostate Cancer and Provides a Regional Panel of Novel DNA Methylation Cancer Biomarkers

Author

Devaney, James, primary, Stirzaker, Clare, primary, Qu, Wenjia, primary, Song, Jenny Z., primary, Statham, Aaron L., primary, Patterson, Kate I., primary, Horvath, Lisa G., primary, Tabor, Bruce, primary, Coolen, Marcel W., primary, Hulf, Toby, primary, Kench, James G., primary, Henshall, Susan M., primary, Pe Benito, Ruth, primary, Haynes, Anne-Maree, primary, Mayor, Regina, primary, Peinado, Miguel A., primary, Sutherland, Robert L., primary, and Clark, Susan J., primary

Published
2023
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21. Methylome and transcriptome maps of human visceral and subcutaneous adipocytes reveal key epigenetic differences at developmental genes

Author

Bradford, Stephen T., Nair, Shalima S., Statham, Aaron L., van Dijk, Susan J., Peters, Timothy J., Anwar, Firoz, French, Hugh J., von Martels, Julius Z. H., Sutcliffe, Brodie, Maddugoda, Madhavi P., Peranec, Michelle, Varinli, Hilal, Arnoldy, Rosanna, Buckley, Michael, Ross, Jason P., Zotenko, Elena, Song, Jenny Z., Stirzaker, Clare, Bauer, Denis C., Qu, Wenjia, Swarbrick, Michael M., Lutgers, Helen L., Lord, Reginald V., Samaras, Katherine, Molloy, Peter L., and Clark, Susan J.

Published
2019
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23. Comprehensive methylome sequencing reveals prognostic epigenetic biomarkers for prostate cancer mortality

Author

Pidsley, Ruth, primary, Lam, Dilys, additional, Qu, Wenjia, additional, Peters, Timothy J., additional, Luu, Phuc‐Loi, additional, Korbie, Darren, additional, Stirzaker, Clare, additional, Daly, Roger J., additional, Stricker, Phillip, additional, Kench, James G., additional, Horvath, Lisa G., additional, and Clark, Susan J., additional

Published
2022
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27. Interaction of Epididymal Epithelia and their Secretions with Spermatozoa Supports Functional and Morphological Changes During Long-Term Storage in the Chinese Soft-Shelled Turtle (Pelodiscus sinensis)

Author

Yufei Huang, Imran Tarique, Yang Sheng, Waseem Ali Vistro, Quisheng Chen, Xuebing Bai, Ping Yang, Mansoor Tariq, and Qu Wenjia

Subjects
endocrine system, 0303 health sciences, 030219 obstetrics & reproductive medicine, urogenital system, Endoplasmic reticulum, Apocrine, Holocrine, Biology, Epididymis, Sperm, Sperm Preservation, Cell biology, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Cytoplasm, Lipid droplet, medicine, Instrumentation, reproductive and urinary physiology, 030304 developmental biology
Abstract

Post-testicular maturation of spermatozoa is crucial for attaining the morphological and functional capabilities needed for successful fertilization. Epididymal epithelia offer a favorable environment for spermatozoa that are stored long term in the turtle epididymis; however, sperm–epithelial interactions during storage, which are enormously important for sperm functional and morphological maturation, are still largely unknown in turtles. The present study examined the epididymis during the sperm-storage period (November–April) in the Chinese soft-shelled turtle (Pelodiscus sinensis). Light and transmission electron microscopy were used to determine the cellular features of each epididymal segment (caput, corpus, and cauda) and their epithelial interactions with the spermatozoa. Spermatozoa were mainly located in the lumena of caput, corpus, and cauda epididymides. Numerous spermatozoa were bound to apical surfaces of the epithelia, and several were even embedded in the epithelial cytoplasm of the caput and corpus epididymides. No embedded spermatozoa were found in the cauda epididymis. In all epididymal segments, principal and clear cells showed the synthetic activity, evidenced by a well-developed endoplasmic reticulum network and high and low electron-dense secretory materials, respectively. Principal and clear cells in the caput and corpus segments showed embedded spermatozoa in electron-dense secretions and in the lipid droplets within the cytoplasm. No lysosomes were observed around the embedded spermatozoa. The lumena of the caput and corpus segments showed few apocrine and low electron density secretions. In the lumen of the cauda epididymidis, different secretions, such as holocrine with low and high electron density and their fragmentation, apocrine, and dictyosome, were found and are summarized. Altogether, sperm physical interactions with secretions either in the cytoplasm of epithelium or in the lumen may support the viability, morphological maintenance, and transfer of various proteins involved in long-term sperm storage in the turtle. This interaction could help us to understand the mechanisms of long-term sperm storage and provide more insights into the reproductive strategies of turtle sperm preservation.

Published
2020

28. GUIDE: a randomised non-comparative phase II trial of biomarker-driven intermittent docetaxel versus standard-of-care docetaxel in metastatic castration-resistant prostate cancer (clinical trial protocol)

Author

Conduit, Ciara, primary, Mak, Blossom, additional, Qu, Wenjia, additional, Lulio, Juliana Di, additional, Burder, Ronan, additional, Bressel, Matthias, additional, Cusick, Thomas, additional, Dhillon, Haryana M., additional, Lourenço, Richard De Abreu, additional, Underhill, Craig, additional, Torres, Javier, additional, Crumbaker, Megan, additional, Honeyball, Florian, additional, Linton, Anthony, additional, Allen, Ray, additional, Davis, Ian D., additional, Clark, Susan J., additional, Horvath, Lisa G., additional, and Mahon, Kate L., additional

Published
2022
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29. Interaction of Epididymal Epithelia and their Secretions with Spermatozoa Supports Functional and Morphological Changes During Long-Term Storage in the Chinese Soft-Shelled Turtle (

Author

Imran, Tarique, Mansoor, Tariq, Xuebing, Bai, Qu, Wenjia, Ping, Yang, Yufei, Huang, Yang, Sheng, Waseem Ali, Vistro, and Quisheng, Chen

Subjects
Epididymis, Male, Bodily Secretions, Asian People, Microscopy, Electron, Transmission, Reproduction, Animals, Humans, Epithelial Cells, Lipid Droplets, Spermatozoa, Epithelium, Turtles
Abstract

Post-testicular maturation of spermatozoa is crucial for attaining the morphological and functional capabilities needed for successful fertilization. Epididymal epithelia offer a favorable environment for spermatozoa that are stored long term in the turtle epididymis; however, sperm-epithelial interactions during storage, which are enormously important for sperm functional and morphological maturation, are still largely unknown in turtles. The present study examined the epididymis during the sperm-storage period (November-April) in the Chinese soft-shelled turtle (Pelodiscus sinensis). Light and transmission electron microscopy were used to determine the cellular features of each epididymal segment (caput, corpus, and cauda) and their epithelial interactions with the spermatozoa. Spermatozoa were mainly located in the lumena of caput, corpus, and cauda epididymides. Numerous spermatozoa were bound to apical surfaces of the epithelia, and several were even embedded in the epithelial cytoplasm of the caput and corpus epididymides. No embedded spermatozoa were found in the cauda epididymis. In all epididymal segments, principal and clear cells showed the synthetic activity, evidenced by a well-developed endoplasmic reticulum network and high and low electron-dense secretory materials, respectively. Principal and clear cells in the caput and corpus segments showed embedded spermatozoa in electron-dense secretions and in the lipid droplets within the cytoplasm. No lysosomes were observed around the embedded spermatozoa. The lumena of the caput and corpus segments showed few apocrine and low electron density secretions. In the lumen of the cauda epididymidis, different secretions, such as holocrine with low and high electron density and their fragmentation, apocrine, and dictyosome, were found and are summarized. Altogether, sperm physical interactions with secretions either in the cytoplasm of epithelium or in the lumen may support the viability, morphological maintenance, and transfer of various proteins involved in long-term sperm storage in the turtle. This interaction could help us to understand the mechanisms of long-term sperm storage and provide more insights into the reproductive strategies of turtle sperm preservation.

Published
2020

34. Serum Free Methylated Glutathione S-transferase 1 DNA Levels, Survival, and Response to Docetaxel in Metastatic, Castration-resistant Prostate Cancer: Post Hoc Analyses of Data from a Phase 3 Trial

Author

Mahon, Kate L., primary, Qu, Wenjia, additional, Lin, Hui-Ming, additional, Spielman, Calan, additional, Cain, Daniel, additional, Jacobs, Cindy, additional, Stockler, Martin R., additional, Higano, Celestia S., additional, de Bono, Johann S., additional, Chi, Kim N., additional, Clark, Susan J., additional, and Horvath, Lisa Glen, additional

Published
2019
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35. DNA Hypermethylation Encroachment at CpG Island Borders in Cancer Is Predisposed by H3K4 Monomethylation Patterns

Author

Skvortsova, Ksenia, primary, Masle-Farquhar, Etienne, additional, Luu, Phuc-Loi, additional, Song, Jenny Z., additional, Qu, Wenjia, additional, Zotenko, Elena, additional, Gould, Cathryn M., additional, Du, Qian, additional, Peters, Timothy J., additional, Colino-Sanguino, Yolanda, additional, Pidsley, Ruth, additional, Nair, Shalima S., additional, Khoury, Amanda, additional, Smith, Grady C., additional, Miosge, Lisa A., additional, Reed, Joanne H., additional, Kench, James G., additional, Rubin, Mark A., additional, Horvath, Lisa, additional, Bogdanovic, Ozren, additional, Lim, Sue Mei, additional, Polo, Jose M., additional, Goodnow, Christopher C., additional, Stirzaker, Clare, additional, and Clark, Susan J., additional

Published
2019
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36. Evaluation of cross-platform and interlaboratory concordance via consensus modelling of genomic measurements

Author

Peters, Timothy J, primary, French, Hugh J, additional, Bradford, Stephen T, additional, Pidsley, Ruth, additional, Stirzaker, Clare, additional, Varinli, Hilal, additional, Nair, Shalima, additional, Qu, Wenjia, additional, Song, Jenny, additional, Giles, Katherine A, additional, Statham, Aaron L, additional, Speirs, Helen, additional, Speed, Terence P, additional, and Clark, Susan J, additional

Published
2018
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37. Enduring epigenetic landmarks define the cancer microenvironment

Author

Pidsley, Ruth, primary, Lawrence, Mitchell G., additional, Zotenko, Elena, additional, Niranjan, Birunthi, additional, Statham, Aaron, additional, Song, Jenny, additional, Chabanon, Roman M., additional, Qu, Wenjia, additional, Wang, Hong, additional, Richards, Michelle, additional, Nair, Shalima S., additional, Armstrong, Nicola J., additional, Nim, Hieu T., additional, Papargiris, Melissa, additional, Balanathan, Preetika, additional, French, Hugh, additional, Peters, Timothy, additional, Norden, Sam, additional, Ryan, Andrew, additional, Pedersen, John, additional, Kench, James, additional, Daly, Roger J., additional, Horvath, Lisa G., additional, Stricker, Phillip, additional, Frydenberg, Mark, additional, Taylor, Renea A., additional, Stirzaker, Clare, additional, Risbridger, Gail P., additional, and Clark, Susan J., additional

Published
2018
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38. Replication timing shapes the cancer epigenome and the nature of chromosomal rearrangements

Author

Du, Qian, primary, Bert, Saul A., additional, Armstrong, Nicola J., additional, Caldon, C. Elizabeth, additional, Song, Jenny Z., additional, Nair, Shalima S., additional, Gould, Cathryn M., additional, Luu, Phuc Loi, additional, Khoury, Amanda, additional, Qu, Wenjia, additional, Zotenko, Elena, additional, Stirzaker, Clare, additional, and Clark, Susan J., additional

Published
2018
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39. Acetylated histone variant H2A.Z is involved in the activation of neo-enhancers in prostate cancer

Author

Valdés-Mora, Fátima, primary, Gould, Cathryn M., additional, Colino-Sanguino, Yolanda, additional, Qu, Wenjia, additional, Song, Jenny Z., additional, Taylor, Kylie M., additional, Buske, Fabian A., additional, Statham, Aaron L., additional, Nair, Shalima S., additional, Armstrong, Nicola J., additional, Kench, James G., additional, Lee, Kenneth M. L., additional, Horvath, Lisa G., additional, Qiu, Minru, additional, Ilinykh, Alexei, additional, Yeo-Teh, Nicole S., additional, Gallego-Ortega, David, additional, Stirzaker, Clare, additional, and Clark, Susan J., additional

Published
2017
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40. Post hoc analysis of a phase III study to test the association between circulating methylated glutathione s transferase (mGSTP1) DNA levels and response to docetaxel (DTX) in metastatic castration resistant prostate cancer (mCRPC).

Author

Mahon, Kate Lynette, primary, Qu, Wenjia, additional, Lin, Hui-Ming, additional, Spielman, Calan, additional, Cain, Daniel, additional, Jacobs, Cindy, additional, Chi, Kim N., additional, De Bono, Johann S., additional, Higano, Celestia S., additional, Clark, Susan J., additional, and Horvath, Lisa, additional

Published
2017
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41. Quantitative comparison of DNA methylation assays for biomarker development and clinical applications

Author

Bock, Christoph, Halbritter, Florian, Carmona, Francisco J., Tierling, Sascha, Datlinger, Paul, Assenov, Yassen, Berdasco, María, Bergmann, Anke K., Booher, Keith, Busato, Florence, Campan, Mihaela, Dahl, Christina, Dahmcke, Christina M., Diep, Dinh, Fernández, Agustín F., Gerhauser, Clarissa, Haake, Andrea, Heilmann, Katharina, Holcomb, Thomas, Hussmann, Dianna, Ito, Mitsuteru, Kläver, Ruth, Kreutz, Martin, Kulis, Marta, López, Virginia, Nair, Shalima S., Paul, Dirk S., Plongthongkum, Nongluk, Qu, Wenjia, Queirós, Ana C., Reinicke, Frank, Sauter, Guido, Schlomm, Thorsten, Statham, Aaron, Stirzaker, Clare, Strogantsev, Ruslan, Urdinguio, Rocío G., Walter, Kimberly, Weichenhan, Dieter, Weisenberger, Daniel J., Beck, Stephan, Clark, Susan J., Esteller, Manel, Ferguson-Smith, Anne C., Fraga, Mario F., Guldberg, Per, Lotte Hansen, Lise, Laird, Peter W., Martín, José Ignacio, Nygren, Anders O. H., Peist, Ralf, Plass, Christoph, Shames, David S., Siebert, Reiner, Sun, Xueguang, Tost, Jörg, Walter, Jörn, Zhang, Kun, Biotechnology and Biological Sciences Research Council (UK), Federal Ministry of Education and Research (Germany), National Institute on Mental Health (US), European Commission, Deutsches Krebsforschungszentrum, and Universitat de Barcelona

Subjects
0301 basic medicine, Genetic Markers, BLUEPRINT consortium, ADN, MathematicsofComputing_GENERAL, Biomedical Engineering, ComputingMilieux_LEGALASPECTSOFCOMPUTING, Bioengineering, Computational biology, Biology, Bioinformatics, Applied Microbiology and Biotechnology, Sensitivity and Specificity, 03 medical and health sciences, InformationSystems_MODELSANDPRINCIPLES, Diagnòstic, MD Multidisciplinary, Diagnosis, Promoter Regions, Genetic, DNA Modification Methylases, ComputingMilieux_THECOMPUTINGPROFESSION, Biochemical markers, TheoryofComputation_GENERAL, High-Throughput Nucleotide Sequencing, Reproducibility of Results, DNA, DNA Methylation, 3. Good health, High-Throughput Screening Assays, Biomarker, 030104 developmental biology, CpG site, Marcadors bioquímics, DNA methylation, Molecular Medicine, Algorithms, Biotechnology
Abstract

The BLUEPRINT consortium, DNA methylation patterns are altered in numerous diseases and often correlate with clinically relevant information such as disease subtypes, prognosis and drug response. With suitable assays and after validation in large cohorts, such associations can be exploited for clinical diagnostics and personalized treatment decisions. Here we describe the results of a community-wide benchmarking study comparing the performance of all widely used methods for DNA methylation analysis that are compatible with routine clinical use. We shipped 32 reference samples to 18 laboratories in seven different countries. Researchers in those laboratories collectively contributed 21 locus-specific assays for an average of 27 predefined genomic regions, as well as six global assays. We evaluated assay sensitivity on low-input samples and assessed the assays' ability to discriminate between cell types. Good agreement was observed across all tested methods, with amplicon bisulfite sequencing and bisulfite pyrosequencing showing the best all-round performance. Our technology comparison can inform the selection, optimization and use of DNA methylation assays in large-scale validation studies, biomarker development and clinical diagnostics., This work was performed in the context of the BLUEPRINT project (European Union’s Seventh Framework Programme grant agreement 282510), which funded the study logistics and the integrative data analysis. The assay costs were paid by the contributing laboratories using institutional funds and the following grants: BBSRC BB/G020930/1, BBSRC BB/G020930/1, BMBF 01KU1001A, BMBF 01KU1002A, BMBF 01KU1216F, EU-FP7 282510, FWF I 1575-B19, NHMRC 1063559, NHMRC 1088144 and the DKFZ Graduate School.

Published
2015

42. Evaluation of cross-platform and interlaboratory concordance via consensus modelling of genomic measurements.

Author

Peters, Timothy J, Pidsley, Ruth, Nair, Shalima, Qu, Wenjia, Song, Jenny, Giles, Katherine A, Statham, Aaron L, French, Hugh J, Bradford, Stephen T, Stirzaker, Clare, Clark, Susan J, Varinli, Hilal, Speirs, Helen, and Speed, Terence P

Subjects
CONCORDANCES, GENOMICS, NUCLEIC acids, MICROARRAY technology, NUCLEOTIDE sequencing
Abstract

Motivation A synoptic view of the human genome benefits chiefly from the application of nucleic acid sequencing and microarray technologies. These platforms allow interrogation of patterns such as gene expression and DNA methylation at the vast majority of canonical loci, allowing granular insights and opportunities for validation of original findings. However, problems arise when validating against a "gold standard" measurement, since this immediately biases all subsequent measurements towards that particular technology or protocol. Since all genomic measurements are estimates, in the absence of a "gold standard" we instead empirically assess the measurement precision and sensitivity of a large suite of genomic technologies via a consensus modelling method called the row-linear model. This method is an application of the American Society for Testing and Materials Standard E691 for assessing interlaboratory precision and sources of variability across multiple testing sites. Both cross-platform and cross-locus comparisons can be made across all common loci, allowing identification of technology- and locus-specific tendencies. Results We assess technologies including the Infinium MethylationEPIC BeadChip, whole genome bisulfite sequencing (WGBS), two different RNA-Seq protocols (PolyA+ and Ribo-Zero) and five different gene expression array platforms. Each technology thus is characterised herein, relative to the consensus. We showcase a number of applications of the row-linear model, including correlation with known interfering traits. We demonstrate a clear effect of cross-hybridisation on the sensitivity of Infinium methylation arrays. Additionally, we perform a true interlaboratory test on a set of samples interrogated on the same platform across twenty-one separate testing laboratories. Availability and implementation A full implementation of the row-linear model, plus extra functions for visualisation, are found in the R package consensus at https://github.com/timpeters82/consensus. Supplementary information Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Published
2019
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43. Quantitative comparison of DNA methylation assays for biomarker development and clinical applications

Author

Biotechnology and Biological Sciences Research Council (UK), Federal Ministry of Education and Research (Germany), National Institute of Mental Health (US), European Commission, Deutsches Krebsforschungszentrum, Bock, Christoph, Halbritter, Florian, Carmona, Francisco J., Tierling, Sascha, Datlinger, Paul, Assenov, Yassen, Berdasco, María, Bergmann, Anke K., Booher, Keith, Busato, Florence, Campan, Mihaela, Dahl, Christina, Dahmcke, Christina M., Diep, Dinh, Fernández, Agustín F., Gerhauser, Clarissa, Haake, Andrea, Heilmann, Katharina, Holcomb, Thomas, Hussmann, Dianna, Ito, Mitsuteru, Kläver, Ruth, Kreutz, Martin, Kulis, Marta, López, Virginia, Nair, Shalima S., Paul, Dirk S., Plongthongkum, Nongluk, Qu, Wenjia, Queirós, Ana C., Reinicke, Frank, Sauter, Guido, Schlomm, Thorsten, Statham, Aaron, Stirzaker, Clare, Strogantsev, Ruslan, Urdinguio, Rocío G., Walter, Kimberly, Weichenhan, Dieter, Weisenberger, Daniel J., Beck, Stephan, Clark, Susan J., Esteller, Manel, Ferguson-Smith, Anne C., Fraga, Mario F., Guldberg, Per, Lotte Hansen, Lise, Laird, Peter W., Martín, José Ignacio, Nygren, Anders O. H., Peist, Ralf, Plass, Christoph, Shames, David S., Siebert, Reiner, Sun, Xueguang, Tost, Jörg, Walter, Jörn, Zhang, Kun, Biotechnology and Biological Sciences Research Council (UK), Federal Ministry of Education and Research (Germany), National Institute of Mental Health (US), European Commission, Deutsches Krebsforschungszentrum, Bock, Christoph, Halbritter, Florian, Carmona, Francisco J., Tierling, Sascha, Datlinger, Paul, Assenov, Yassen, Berdasco, María, Bergmann, Anke K., Booher, Keith, Busato, Florence, Campan, Mihaela, Dahl, Christina, Dahmcke, Christina M., Diep, Dinh, Fernández, Agustín F., Gerhauser, Clarissa, Haake, Andrea, Heilmann, Katharina, Holcomb, Thomas, Hussmann, Dianna, Ito, Mitsuteru, Kläver, Ruth, Kreutz, Martin, Kulis, Marta, López, Virginia, Nair, Shalima S., Paul, Dirk S., Plongthongkum, Nongluk, Qu, Wenjia, Queirós, Ana C., Reinicke, Frank, Sauter, Guido, Schlomm, Thorsten, Statham, Aaron, Stirzaker, Clare, Strogantsev, Ruslan, Urdinguio, Rocío G., Walter, Kimberly, Weichenhan, Dieter, Weisenberger, Daniel J., Beck, Stephan, Clark, Susan J., Esteller, Manel, Ferguson-Smith, Anne C., Fraga, Mario F., Guldberg, Per, Lotte Hansen, Lise, Laird, Peter W., Martín, José Ignacio, Nygren, Anders O. H., Peist, Ralf, Plass, Christoph, Shames, David S., Siebert, Reiner, Sun, Xueguang, Tost, Jörg, Walter, Jörn, and Zhang, Kun

Abstract

DNA methylation patterns are altered in numerous diseases and often correlate with clinically relevant information such as disease subtypes, prognosis and drug response. With suitable assays and after validation in large cohorts, such associations can be exploited for clinical diagnostics and personalized treatment decisions. Here we describe the results of a community-wide benchmarking study comparing the performance of all widely used methods for DNA methylation analysis that are compatible with routine clinical use. We shipped 32 reference samples to 18 laboratories in seven different countries. Researchers in those laboratories collectively contributed 21 locus-specific assays for an average of 27 predefined genomic regions, as well as six global assays. We evaluated assay sensitivity on low-input samples and assessed the assays' ability to discriminate between cell types. Good agreement was observed across all tested methods, with amplicon bisulfite sequencing and bisulfite pyrosequencing showing the best all-round performance. Our technology comparison can inform the selection, optimization and use of DNA methylation assays in large-scale validation studies, biomarker development and clinical diagnostics.

Published
2016

44. GUIDE: A randomized non-comparative phase II trial of biomarker-driven intermittent docetaxel versus standard-of-care docetaxel in metastatic castration-resistant prostate cancer (ANZUP 1903).

Author

Conduit, Ciara, Mak, Blossom, Qu, Wenjia, Yeung, Theresa, Bressel, Mathias, Cusick, Thomas, Dhillon, Haryana M., De Abreu Lourenço, Richard, Underhill, Craig, Torres, Javier, Crumbaker, Megan, Honeyball, Florian, Linton, Anthony, Sewak, Sanjeev, Chau, Nguyen Minh Hieu, Allen, Ray, Davis, Ian D., Clark, Susan J., Horvath, Lisa, and Mahon, Kate Lynette

Published
2023
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45. Methylome sequencing in triple-negative breast cancer reveals distinct methylation clusters with prognostic value

Author

Stirzaker, Clare, primary, Zotenko, Elena, additional, Song, Jenny Z., additional, Qu, Wenjia, additional, Nair, Shalima S., additional, Locke, Warwick J., additional, Stone, Andrew, additional, Armstong, Nicola J., additional, Robinson, Mark D., additional, Dobrovic, Alexander, additional, Avery-Kiejda, Kelly A., additional, Peters, Kate M., additional, French, Juliet D., additional, Stein, Sandra, additional, Korbie, Darren J., additional, Trau, Matt, additional, Forbes, John F., additional, Scott, Rodney J., additional, Brown, Melissa A., additional, Francis, Glenn D., additional, and Clark, Susan J., additional

Published
2015
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46. Circulating microRNAs associated with docetaxel-resistant castration resistant prostate cancer.

Author

Horvath, Lisa, primary, Lin, Hui-Ming, additional, Castillo, Lesley, additional, Mahon, Kate Lynette, additional, Chiam, Karen, additional, Lee, Brian Yong, additional, Nguyen, Quoc, additional, Qu, Wenjia, additional, Boyer, Michael J., additional, Stockler, Martin R., additional, Pavlakis, Nick, additional, Marx, Gavin M., additional, Hiriyanna Gowda, Girish Mallesara, additional, Gurney, Howard, additional, Clark, Susan J., additional, Swarbrick, Alex, additional, and Daly, Roger J., additional

Published
2014
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47. GWAS of DNA methylation variation within imprinting control regions suggests parent-of-origin association

Author

Rentería, Miguel E., Coolen, Marcel W., Statham, Aaron L., Choi, R. Seong Min, Qu, Wenjia, Campbell, Megan J., Smith, Sara, Henders, Anjali K., Montgomery, Grant W., Clark, Susan J., Martin, Nicholas G., Medland, Sarah E., Rentería, Miguel E., Coolen, Marcel W., Statham, Aaron L., Choi, R. Seong Min, Qu, Wenjia, Campbell, Megan J., Smith, Sara, Henders, Anjali K., Montgomery, Grant W., Clark, Susan J., Martin, Nicholas G., and Medland, Sarah E.

Abstract

Imprinting control regions (ICRs) play a fundamental role in establishing and maintaining the non-random monoallelic expression of certain genes, via common regulatory elements such as non-coding RNAs and differentially methylated regions (DMRs) of DNA. We recently surveyed DNA methylation levels within four ICRs (H19-ICR, IGF2-DMR, KvDMR, and NESPAS-ICR) in whole-blood genomic DNA from 128 monozygotic (MZ) and 128 dizygotic (DZ) human twin pairs. Our analyses revealed high individual variation and intra-domain covariation in methylation levels across CpGs and emphasized the interaction between epigenetic variation and the underlying genetic sequence in a parent-of-origin fashion. Here, we extend our analysis to conduct two genome-wide screenings of single nucleotide polymorphisms (SNPs) underlying either intra-domain covariation or parent-of-origin-dependent association with methylation status at individual CpG sites located within ICRs. Although genome-wide significance was not surpassed due to sample size limitations, the most significantly associated SNPs found through multiple-trait genome-wide association (MQFAM) included the previously described rs10732516, which is located in the vicinity of the H19-ICR. Similarly, we identified an association between rs965808 and methylation status within the NESPAS-ICR. This SNP is positioned within an intronic region of the overlapping genes GNAS and GNAS-AS1, which are imprinted genes regulated by the NESPAS-ICR. Sixteen other SNPs located in regions apart from the analyzed regions displayed suggestive association with intra-domain methylation. Additionally, we identified 13 SNPs displaying parent-of-origin association with individual methylation sites through family-based association testing. In this exploratory study, we show the value and feasibility of using alternative GWAS approaches in the study of the interaction between epigenetic state and genetic sequence within imprinting regulatory domains. Despite the re

Published
2013

48. Impact of the genome on the epigenome is manifested in DNA methylation patterns of imprinted regions in monozygotic and dizygotic twins

Author

Coolen, Marcel W., Statham, Aaron L., Qu, Wenjia, Campbell, Megan J., Henders, Anjali K., Montgomery, Grant W., Martin, Nick G., Clark, Susan J., Coolen, Marcel W., Statham, Aaron L., Qu, Wenjia, Campbell, Megan J., Henders, Anjali K., Montgomery, Grant W., Martin, Nick G., and Clark, Susan J.

Abstract

One of the best studied read-outs of epigenetic change is the differential expression of imprinted genes, controlled by differential methylation of imprinted control regions (ICRs). To address the impact of genotype on the epigenome, we performed a detailed study in 128 pairs of monozygotic (MZ) and 128 pairs of dizygotic (DZ) twins, interrogating the DNA methylation status of the ICRs of IGF2, H19, KCNQ1, GNAS and the non-imprinted gene RUNX1. While we found a similar overall pattern of methylation between MZ and DZ twins, we also observed a high degree of variability in individual CpG methylation levels, notably at the H19/IGF2 loci. A degree of methylation plasticity independent of the genome sequence was observed, with both local and regional CpG methylation changes, discordant between MZ and DZ individual pairs. However, concordant gains or losses of methylation, within individual twin pairs were more common in MZ than DZ twin pairs, indicating that de novo and/or maintenance methylation is influenced by the underlying DNA sequence. Specifically, for the first time we showed that the rs10732516 [A] polymorphism, located in a critical CTCF binding site in the H19 ICR locus, is strongly associated with increased hypermethylation of specific CpG sites in the maternal H19 allele. Together, our results highlight the impact of the genome on the epigenome and demonstrate that while DNA methylation states are tightly maintained between genetically identical and related individuals, there remains considerable epigenetic variation that may contribute to disease susceptibility.

Published
2011

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