201 results on '"Heyn, H."'
Search Results
2. Human DNA methylomes of neurodegenerative diseases show common epigenomic patterns
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Sanchez-Mut, J V, Heyn, H, Vidal, E, Moran, S, Sayols, S, Delgado-Morales, R, Schultz, M D, Ansoleaga, B, Garcia-Esparcia, P, Pons-Espinal, M, de Lagran, M M, Dopazo, J, Rabano, A, Avila, J, Dierssen, M, Lott, I, Ferrer, I, Ecker, J R, and Esteller, M
- Published
- 2016
3. 14P Integrated modelling of T cell repertoires to identify clonotype signatures of ICI response
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Melero, J.L., primary, Colom-Sanmartí, B., additional, Mendizabal-Sasieta, A., additional, Perron, U., additional, Grzelak, M., additional, Pravdyvets, D., additional, Soto, M., additional, Nieto, J.C., additional, Vidal, S., additional, Tejpar, S., additional, Borcherding, N., additional, Rigol, E. Planas, additional, and Heyn, H., additional
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- 2023
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4. DualMET andERBB inhibition overcomes intratumor plasticity in osimertinib-resistant-advanced non-small-cell lung cancer (NSCLC)
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Martinez-Marti, A., Felip, E., Matito, J., Mereu, E., Navarro, A., Cedrés, S., Pardo, N., Martinez de Castro, A., Remon, J., Miquel, J.M., Guillaumet-Adkins, A., Nadal, E., Rodriguez-Esteban, G., Arqués, O., Fasani, R., Nuciforo, P., Heyn, H., Villanueva, A., Palmer, H.G., and Vivancos, A.
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- 2017
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5. 561P Liquid biopsy tracking of immunotherapy-induced T cell dynamics in MSS colorectal and endometrial tumors.
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Heyn, H., Melero, J.L., Deuner, G., Argota, I. Baraibar, Grzelak, M., Caratu, G., Duran, C. Garcia, Béjar, J.F. Grau, Illescas, D.G., Madrid, L. Fariñas, Nieto, P., Morabito, S., Rotem, A., Casbas-Hernandez, P., Gros, A., Tabernero, J., Oaknin, A., Sachica, J.N., Borcherding, N., and Fernandez, M.E. Elez
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ENDOMETRIAL tumors , *COLON tumors , *T cells , *BIOPSY , *LIQUIDS - Published
- 2024
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6. A single-cell expression atlas of human AML-LScs unravels the contribution of HIF pathway and its therapeutic potential
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Velasco-Hernandez, T, additional, Trincado, JL, additional, Vinyoles, M, additional, Closa, A, additional, Molina, O, additional, Velten, L, additional, Bueno, C, additional, Eyras, E, additional, Heyn, H, additional, and Menendez, P, additional
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- 2022
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7. Mex3a marks drug-tolerant persister colorectal cancer cells that mediate relapse after chemotherapy
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Álvarez-Varela, A., Novellasdemunt, l., Barriga, F.M., Hernando-Momblona, X., Cañellas-Socias, A., Cano-Crespo, S., Sevillano, M., Cortina, C., Stork, d., Morral, C., Turon, G., Slebe, F., Jiménez-Gracia, L., Caratù, G., Jung, P., Stassi, G., Heyn, H., Tauriello, D.V.F., Mateo, L., Tejpar, S., Sancho, E., E., S.-O., Batll, A.E., Álvarez-Varela, A., Novellasdemunt, l., Barriga, F.M., Hernando-Momblona, X., Cañellas-Socias, A., Cano-Crespo, S., Sevillano, M., Cortina, C., Stork, d., Morral, C., Turon, G., Slebe, F., Jiménez-Gracia, L., Caratù, G., Jung, P., Stassi, G., Heyn, H., Tauriello, D.V.F., Mateo, L., Tejpar, S., Sancho, E., E., S.-O., and Batll, A.E.
- Abstract
Item does not contain fulltext
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- 2022
8. Metastatic recurrence in colorectal cancer arises from residual EMP1+ cells
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Cañellas-Socias, A., Cortina, C., Hernando-Momblona, X., Palomo-Ponce, S., Mulholland, E.J., Turon, G., Mateo, L., Conti, S., Roman, O., Sevillano, M., Slebe, F., Stork, d., Caballé-Mestres, A., Berenguer-Llergo, A., Álvarez-Varela, A., Fenderico, A., Novellasdemunt, l., Jiménez-Gracia, L., Sipka, T., Bardia, L., Lorden, P., Colombelli, J., Heyn, H., Trepat, X., Tejpar, S., Sancho, E., Tauriello, D.V.F., Leedham, S., Stephan-Otto Attolini, C., Batlle, E., Cañellas-Socias, A., Cortina, C., Hernando-Momblona, X., Palomo-Ponce, S., Mulholland, E.J., Turon, G., Mateo, L., Conti, S., Roman, O., Sevillano, M., Slebe, F., Stork, d., Caballé-Mestres, A., Berenguer-Llergo, A., Álvarez-Varela, A., Fenderico, A., Novellasdemunt, l., Jiménez-Gracia, L., Sipka, T., Bardia, L., Lorden, P., Colombelli, J., Heyn, H., Trepat, X., Tejpar, S., Sancho, E., Tauriello, D.V.F., Leedham, S., Stephan-Otto Attolini, C., and Batlle, E.
- Abstract
Item does not contain fulltext
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- 2022
9. Cohesin couples transcriptional bursting probabilities of inducible enhancers and promoters.
- Author
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Robles-Rebollo, I, Cuartero, S, Canellas-Socias, A, Wells, S, Karimi, MM, Mereu, E, Chivu, AG, Heyn, H, Whilding, C, Dormann, D, Marguerat, S, Rioja, I, Prinjha, RK, Stumpf, MPH, Fisher, AG, Merkenschlager, M, Robles-Rebollo, I, Cuartero, S, Canellas-Socias, A, Wells, S, Karimi, MM, Mereu, E, Chivu, AG, Heyn, H, Whilding, C, Dormann, D, Marguerat, S, Rioja, I, Prinjha, RK, Stumpf, MPH, Fisher, AG, and Merkenschlager, M
- Abstract
Innate immune responses rely on inducible gene expression programmes which, in contrast to steady-state transcription, are highly dependent on cohesin. Here we address transcriptional parameters underlying this cohesin-dependence by single-molecule RNA-FISH and single-cell RNA-sequencing. We show that inducible innate immune genes are regulated predominantly by an increase in the probability of active transcription, and that probabilities of enhancer and promoter transcription are coordinated. Cohesin has no major impact on the fraction of transcribed inducible enhancers, or the number of mature mRNAs produced per transcribing cell. Cohesin is, however, required for coupling the probabilities of enhancer and promoter transcription. Enhancer-promoter coupling may not be explained by spatial proximity alone, and at the model locus Il12b can be disrupted by selective inhibition of the cohesinopathy-associated BET bromodomain BD2. Our data identify discrete steps in enhancer-mediated inducible gene expression that differ in cohesin-dependence, and suggest that cohesin and BD2 may act on shared pathways.
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- 2022
10. The emerging landscape of spatial profiling technologies
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Moffitt, J. R., Lundberg, Emma, Heyn, H., Moffitt, J. R., Lundberg, Emma, and Heyn, H.
- Abstract
Improved scale, multiplexing and resolution are establishing spatial nucleic acid and protein profiling methods as a major pillar for cellular atlas building of complex samples, from tissues to full organisms. Emerging methods yield omics measurements at resolutions covering the nano- to microscale, enabling the charting of cellular heterogeneity, complex tissue architectures and dynamic changes during development and disease. We present an overview of the developing landscape of in situ spatial genome, transcriptome and proteome technologies, exemplify their impact on cell biology and translational research, and discuss current challenges for their community-wide adoption. Among many transformative applications, we envision that spatial methods will map entire organs and enable next-generation pathology., QC 20230421
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- 2022
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11. Dual MET and ERBB inhibition overcomes intratumor plasticity in osimertinib-resistant-advanced non-small-cell lung cancer (NSCLC)
- Author
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Martinez-Marti, A., Felip, E., Matito, J., Mereu, E., Navarro, A., Cedrés, S., Pardo, N., Martinez de Castro, A., Remon, J., Miquel, J. M., Guillaumet-Adkins, A., Nadal, E., Rodriguez-Esteban, G., Arqués, O., Fasani, R., Nuciforo, P., Heyn, H., Villanueva, A., Palmer, H. G., and Vivancos, A.
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- 2017
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12. VEDLIoT: Very Efficient Deep Learning in IoT
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Kaiser, M., primary, Griessl, R., additional, Kucza, N., additional, Haumann, C., additional, Tigges, L., additional, Mika, K., additional, Hagemeyer, J., additional, Porrmann, F., additional, Ruckert, U., additional, vor dem Berge, M., additional, Krupop, S., additional, Porrmann, M., additional, Tassemeier, M., additional, Trancoso, P., additional, Qararyah, F., additional, Zouzoula, S., additional, Casimiro, A., additional, Bessani, A., additional, Cecilio, J., additional, Andersson, S., additional, Brunnegard, O., additional, Eriksson, O., additional, Weiss, R., additional, Mcierhofer, F., additional, Salomonsson, H., additional, Malekzadeh, E., additional, Odman, D., additional, Khurshid, A., additional, Felber, P., additional, Pasin, M., additional, Schiavoni, V., additional, Menetrey, J., additional, Gugala, K., additional, Zierhoffer, P., additional, Knauss, E., additional, and Heyn, H., additional
- Published
- 2022
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13. VEDLIoT: Very Efficient Deep Learning in IoT
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Kaiser, Martin, Griessl, René, Kucza, Nils, Haumann, Carola, Tigges, Lennart, Mika, Kevin, Hagemeyer, Jens, Porrmann, Florian, Rückert, Ulrich, vor dem Berge, M., Krupop, S., Porrmann, M., Tassemeier, M., Trancoso, P., Qararyah, F., Zouzoula, S., Casimiro, A., Bessani, A., Cecilio, J., Andersson, S., Brunnegard, O., Eriksson, O., Weiss, R., Mcierhofer, F., Salomonsson, H., Malekzadeh, E., Odman, D., Khurshid, A., Felber, P., Pasin, M., Schiavoni, V., Menetrey, J., Gugala, K., Zierhoffer, P., Knauss, E., Heyn, H., and ARRAY(0xab8ee90)
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Performance (cs.PF) ,FOS: Computer and information sciences ,Computer Science - Cryptography and Security ,Computer Science - Performance ,Computer Science - Distributed, Parallel, and Cluster Computing ,Hardware Architecture (cs.AR) ,Distributed, Parallel, and Cluster Computing (cs.DC) ,Computer Science - Hardware Architecture ,Cryptography and Security (cs.CR) - Abstract
The VEDLIoT project targets the development of energy-efficient Deep Learning for distributed AIoT applications. A holistic approach is used to optimize algorithms while also dealing with safety and security challenges. The approach is based on a modular and scalable cognitive IoT hardware platform. Using modular microserver technology enables the user to configure the hardware to satisfy a wide range of applications. VEDLIoT offers a complete design flow for Next-Generation IoT devices required for collaboratively solving complex Deep Learning applications across distributed systems. The methods are tested on various use-cases ranging from Smart Home to Automotive and Industrial IoT appliances. VEDLIoT is an H2020 EU project which started in November 2020. It is currently in an intermediate stage with the first results available., Comment: This publication incorporates results from the VEDLIoT project, which received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 957197
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- 2022
14. DNMT3A mutations mediate the epigenetic reactivation of the leukemogenic factor MEIS1 in acute myeloid leukemia
- Author
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Ferreira, H J, Heyn, H, Vizoso, M, Moutinho, C, Vidal, E, Gomez, A, Martínez-Cardús, A, Simó-Riudalbas, L, Moran, S, Jost, E, and Esteller, M
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- 2016
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15. LifeTime and improving European healthcare through cell-based interceptive medicine
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Rajewsky, N., Almouzni, G., Gorski, S., Aerts, S., Amit, I., Bertero, M., Bock, C., Bredenoord, A., Cavalli, G., Chiocca, S., Clevers, H., Strooper, B., Eggert, A., Ellenberg, J., Fernández, X., Figlerowicz, M., Gasser, S., Hubner, N., Kjems, J., Knoblich, J., Krabbe, G., Lichter, P., Linnarsson, S., Marine, J., Marioni, J., Marti-Renom, M., Netea, M., Nickel, D., Nollmann, M., Novak, H., Parkinson, H., Piccolo, S., Pinheiro, I., Pombo, A., Popp, C., Reik, W., Roman-Roman, S., Rosenstiel, P., Schultze, J., Stegle, O., Tanay, A., Testa, G., Thanos, D., Theis, F., Torres-Padilla, M., Valencia, A., Vallot, C., van Oudenaarden, A., Vidal, M., Voet, T., Alberi, L., Alexander, S., Alexandrov, T., Arenas, E., Bagni, C., Balderas, R., Bandelli, A., Becher, B., Becker, M., Beerenwinkel, N., Benkirame, M., Beyer, M., Bickmore, W., Biessen, E., Blomberg, N., Blumcke, I., Bodenmiller, B., Borroni, B., Boumpas, D., Bourgeron, T., Bowers, S., Braeken, D., Brooksbank, C., Brose, N., Bruining, H., Bury, J., Caporale, N., Cattoretti, G., Chabane, N., Chneiweiss, H., Cook, S., Curatolo, P., de Jonge, M., Deplancke, B., de Witte, P., Dimmeler, S., Draganski, B., Drews, A., Dumbrava, C., Engelhardt, S., Gasser, T., Giamarellos-Bourboulis, E., Graff, C., Grün, D., Gut, I., Hansson, O., Henshall, D., Herland, A., Heutink, P., Heymans, S., Heyn, H., Huch, M., Huitinga, I., Jackowiak, P., Jongsma, K., Journot, L., Junker, J., Katz, S., Kehren, J., Kempa, S., Kirchhof, P., Klein, C., Koralewska, N., Korbel, J., Kühnemund, M., Lamond, A., Lauwers, E., Le Ber, I., Leinonen, V., Tobon, A., Lundberg, E., Lunkes, A., Maatz, H., Mann, M., Marelli, L., Matser, V., Matthews, P., Mechta-Grigoriou, F., Menon, R., Nielsen, A., Pagani, M., Pasterkamp, R., Pitkänen, A., Popescu, V., Pottier, C., Puisieux, A., Rademakers, R., Reiling, D., Reiner, O., Remondini, D., Ritchie, C., Rohrer, J., Saliba, A., Sanchez-Valle, R., Santosuosso, A., Sauter, A., Scheltema, R., Scheltens, P., Schiller, H., Schneider, A., Seibler, P., Sheehan-Rooney, K., Shields, D., Sleegers, K., Smit, A., Smith, K., Smolders, I., Synofzik, M., Tam, W., Teichmann, S., Thom, M., Turco, M., van Beusekom, H., Vandenberghe, R., den Hoecke, S., de Poel, I., van der Ven, A., van der Zee, J., van Lunzen, J., van Minnebruggen, G., Paesschen, W., van Swieten, J., van Vught, R., Verhage, M., Verstreken, P., Villa, C., Vogel, J., von Kalle, C., Walter, J., Weckhuysen, S., Weichert, W., Wood, L., Ziegler, A., Zipp, F., HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany., Medical Research Council (MRC), UK DRI Ltd, TWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany., Barcelona Supercomputing Center, LifeTime Community Working Groups, Cardiology, Neurology, Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Human genetics, Rajewsky N., Almouzni G., Gorski S.A., Aerts S., Amit I., Bertero M.G., Bock C., Bredenoord A.L., Cavalli G., Chiocca S., Clevers H., De Strooper B., Eggert A., Ellenberg J., Fernandez X.M., Figlerowicz M., Gasser S.M., Hubner N., Kjems J., Knoblich J.A., Krabbe G., Lichter P., Linnarsson S., Marine J.-C., Marioni J.C., Marti-Renom M.A., Netea M.G., Nickel D., Nollmann M., Novak H.R., Parkinson H., Piccolo S., Pinheiro I., Pombo A., Popp C., Reik W., Roman-Roman S., Rosenstiel P., Schultze J.L., Stegle O., Tanay A., Testa G., Thanos D., Theis F.J., Torres-Padilla M.-E., Valencia A., Vallot C., van Oudenaarden A., Vidal M., Voet T., Alberi L., Alexander S., Alexandrov T., Arenas E., Bagni C., Balderas R., Bandelli A., Becher B., Becker M., Beerenwinkel N., Benkirame M., Beyer M., Bickmore W., Biessen E.E.A.L., Blomberg N., Blumcke I., Bodenmiller B., Borroni B., Boumpas D.T., Bourgeron T., Bowers S., Braeken D., Brooksbank C., Brose N., Bruining H., Bury J., Caporale N., Cattoretti G., Chabane N., Chneiweiss H., Cook S.A., Curatolo P., de Jonge M.I., Deplancke B., de Witte P., Dimmeler S., Draganski B., Drews A., Dumbrava C., Engelhardt S., Gasser T., Giamarellos-Bourboulis E.J., Graff C., Grun D., Gut I., Hansson O., Henshall D.C., Herland A., Heutink P., Heymans S.R.B., Heyn H., Huch M., Huitinga I., Jackowiak P., Jongsma K.R., Journot L., Junker J.P., Katz S., Kehren J., Kempa S., Kirchhof P., Klein C., Koralewska N., Korbel J.O., Kuhnemund M., Lamond A.I., Lauwers E., Le Ber I., Leinonen V., Tobon A.L., Lundberg E., Lunkes A., Maatz H., Mann M., Marelli L., Matser V., Matthews P.M., Mechta-Grigoriou F., Menon R., Nielsen A.F., Pagani M., Pasterkamp R.J., Pitkanen A., Popescu V., Pottier C., Puisieux A., Rademakers R., Reiling D., Reiner O., Remondini D., Ritchie C., Rohrer J.D., Saliba A.-E., Sanchez-Valle R., Santosuosso A., Sauter A., Scheltema R.A., Scheltens P., Schiller H.B., Schneider A., Seibler P., Sheehan-Rooney K., Shields D., Sleegers K., Smit A.B., Smith K.G.C., Smolders I., Synofzik M., Tam W.L., Teichmann S., Thom M., Turco M.Y., van Beusekom H.M.M., Vandenberghe R., Van den Hoecke S., Van de Poel I., van der Ven A., van der Zee J., van Lunzen J., van Minnebruggen G., Van Paesschen W., van Swieten J., van Vught R., Verhage M., Verstreken P., Villa C.E., Vogel J., von Kalle C., Walter J., Weckhuysen S., Weichert W., Wood L., Ziegler A.-G., Zipp F., Center for Neurogenomics and Cognitive Research, Functional Genomics, Rajewsky, N, Almouzni, G, Gorski, S, Aerts, S, Amit, I, Bertero, M, Bock, C, Bredenoord, A, Cavalli, G, Chiocca, S, Clevers, H, De Strooper, B, Eggert, A, Ellenberg, J, Fernández, X, Figlerowicz, M, Gasser, S, Hubner, N, Kjems, J, Knoblich, J, Krabbe, G, Lichter, P, Linnarsson, S, Marine, J, Marioni, J, Marti-Renom, M, Netea, M, Nickel, D, Nollmann, M, Novak, H, Parkinson, H, Piccolo, S, Pinheiro, I, Pombo, A, Popp, C, Reik, W, Roman-Roman, S, Rosenstiel, P, Schultze, J, Stegle, O, Tanay, A, Testa, G, Thanos, D, Theis, F, Torres-Padilla, M, Valencia, A, Vallot, C, van Oudenaarden, A, Vidal, M, Voet, T, Cattoretti, G, Alliance for Modulation in Epilepsy, Pharmaceutical and Pharmacological Sciences, Experimental Pharmacology, RS: Carim - H02 Cardiomyopathy, MUMC+: MA Med Staf Spec Cardiologie (9), and Cardiologie
- Subjects
0301 basic medicine ,Male ,Artificial intelligence ,Legislation, Medical ,[SDV]Life Sciences [q-bio] ,Molecular datasets ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,Cell- and Tissue-Based Therapy ,Diseases ,LifeTime Community Working Groups ,Disease ,Biomarkers ,Systems biology ,Health data ,Pharmacology, Toxicology and Pharmaceutics(all) ,0302 clinical medicine ,Conjunts de dades ,ethics [Delivery of Health Care] ,Health care ,Pathology ,Medicine ,European healthcare ,BRAIN ,Single-cell multi-omics ,GENE-EXPRESSION ,Multidisciplinary ,methods [Medicine] ,Education, Medical ,Settore BIO/13 ,Intel.ligència artificial ,3. Good health ,ALZHEIMERS-DISEASE ,Europe ,Health ,Management system ,Perspective ,Female ,ddc:500 ,Single-Cell Analysis ,Biomarkers, Diseases, Systems biology ,Complex diseases ,Informàtica::Aplicacions de la informàtica::Bioinformàtica [Àrees temàtiques de la UPC] ,medicine.medical_specialty ,General Science & Technology ,Cells ,MEDLINE ,cell-based interceptive medicine ,LifeTime Initiative ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,Clinical datasets ,Artificial Intelligence ,REVEALS ,LifeTime Community ,standards [Medicine] ,Humans ,OMICS ,RECONSTRUCTION ,Intensive care medicine ,trends [Medicine] ,trends [Delivery of Health Care] ,business.industry ,Disease progression ,standards [Delivery of Health Care] ,methods [Delivery of Health Care] ,030104 developmental biology ,lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4] ,single cell, personalized therapy, machine learning, bioinformatics, systems biology, disease, cell-based interceptive medicine ,Early Diagnosis ,Cardiovascular and Metabolic Diseases ,Human medicine ,business ,Delivery of Health Care ,030217 neurology & neurosurgery ,Cell based - Abstract
Here we describe the LifeTime Initiative, which aims to track, understand and target human cells during the onset and progression of complex diseases, and to analyse their response to therapy at single-cell resolution. This mission will be implemented through the development, integration and application of single-cell multi-omics and imaging, artificial intelligence and patient-derived experimental disease models during the progression from health to disease. The analysis of large molecular and clinical datasets will identify molecular mechanisms, create predictive computational models of disease progression, and reveal new drug targets and therapies. The timely detection and interception of disease embedded in an ethical and patient-centred vision will be achieved through interactions across academia, hospitals, patient associations, health data management systems and industry. The application of this strategy to key medical challenges in cancer, neurological and neuropsychiatric disorders, and infectious, chronic inflammatory and cardiovascular diseases at the single-cell level will usher in cell-based interceptive medicine in Europe over the next decade., The LifeTime initiative is an ambitious, multidisciplinary programme that aims to improve healthcare by tracking individual human cells during disease processes and responses to treatment in order to develop and implement cell-based interceptive medicine in Europe.
- Published
- 2020
16. P018 Myeloid diversity in inflammatory bowel disease revealed by single-cell transcriptomics
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Garrido Trigo, A, primary, Corraliza, A M, additional, Melón-Ardanaz, E, additional, Veny, M, additional, Ordás, I, additional, Ricart, E, additional, Masamunt, M C, additional, Panès, J, additional, Hemberg, M, additional, Mereu, E, additional, Heyn, H, additional, and Azucena, S, additional
- Published
- 2021
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17. Publisher Correction: LifeTime and improving European healthcare through cell-based interceptive medicine (Nature, (2020), 587, 7834, (377-386), 10.1038/s41586-020-2715-9)
- Author
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Rajewsky, N. Almouzni, G. Gorski, S.A. Aerts, S. Amit, I. Bertero, M.G. Bock, C. Bredenoord, A.L. Cavalli, G. Chiocca, S. Clevers, H. De Strooper, B. Eggert, A. Ellenberg, J. Fernández, X.M. Figlerowicz, M. Gasser, S.M. Hubner, N. Kjems, J. Knoblich, J.A. Krabbe, G. Lichter, P. Linnarsson, S. Marine, J.-C. Marioni, J.C. Marti-Renom, M.A. Netea, M.G. Nickel, D. Nollmann, M. Novak, H.R. Parkinson, H. Piccolo, S. Pinheiro, I. Pombo, A. Popp, C. Reik, W. Roman-Roman, S. Rosenstiel, P. Schultze, J.L. Stegle, O. Tanay, A. Testa, G. Thanos, D. Theis, F.J. Torres-Padilla, M.-E. Valencia, A. Vallot, C. van Oudenaarden, A. Vidal, M. Voet, T. Alberi, L. Alexander, S. Alexandrov, T. Arenas, E. Bagni, C. Balderas, R. Bandelli, A. Becher, B. Becker, M. Beerenwinkel, N. Benkirane, M. Beyer, M. Bickmore, W.A. Biessen, E.E.A.L. Blomberg, N. Blumcke, I. Bodenmiller, B. Borroni, B. Boumpas, D.T. Bourgeron, T. Bowers, S. Braeken, D. Brooksbank, C. Brose, N. Bruining, H. Bury, J. Caporale, N. Cattoretti, G. Chabane, N. Chneiweiss, H. Cook, S.A. Curatolo, P. de Jonge, M.I. Deplancke, B. de Witte, P. Dimmeler, S. Draganski, B. Drews, A. Dumbrava, C. Engelhardt, S. Gasser, T. Giamarellos-Bourboulis, E.J. Graff, C. Grün, D. Gut, I.G. Hansson, O. Henshall, D.C. Herland, A. Heutink, P. Heymans, S.R.B. Heyn, H. Huch, M. Huitinga, I. Jackowiak, P. Jongsma, K.R. Journot, L. Junker, J.P. Katz, S. Kehren, J. Kempa, S. Kirchhof, P. Klein, C. Koralewska, N. Korbel, J.O. Kühnemund, M. Lamond, A.I. Lauwers, E. Le Ber, I. Leinonen, V. López-Tobón, A. Lundberg, E. Lunkes, A. Maatz, H. Mann, M. Marelli, L. Matser, V. Matthews, P.M. Mechta-Grigoriou, F. Menon, R. Nielsen, A.F. Pagani, M. Pasterkamp, R.J. Pitkänen, A. Popescu, V. Pottier, C. Puisieux, A. Rademakers, R. Reiling, D. Reiner, O. Remondini, D. Ritchie, C. Rohrer, J.D. Saliba, A.-E. Sanchez-Valle, R. Santosuosso, A. Sauter, A. Scheltema, R.A. Scheltens, P. Schiller, H.B. Schneider, A. Seibler, P. Sheehan-Rooney, K. Shields, D.J. Sleegers, K. Smit, A.B. Smith, K.G.C. Smolders, I. Synofzik, M. Tam, W.L. Teichmann, S.A. Thom, M. Turco, M.Y. van Beusekom, H.M.M. Vandenberghe, R. Van den Hoecke, S. van de Poel, I. van der Ven, A. van der Zee, J. van Lunzen, J. van Minnebruggen, G. van Oudenaarden, A. Van Paesschen, W. van Swieten, J.C. van Vught, R. Verhage, M. Verstreken, P. Villa, C.E. Vogel, J. von Kalle, C. Walter, J. Weckhuysen, S. Weichert, W. Wood, L. Ziegler, A.-G. Zipp, F. LifeTime Community Working Groups
- Subjects
ComputingMethodologies_DOCUMENTANDTEXTPROCESSING - Abstract
In this Perspective, owing to an error in the HTML, the surname of author Alejandro López-Tobón of the LifeTime Community Working Groups consortium was indexed as ‘Tobon’ rather than ‘López-Tobón’ and the accents were missing. The HTML version of the original Perspective has been corrected; the PDF and print versions were always correct. © 2021, The Author(s).
- Published
- 2021
18. Building a high-quality Human Cell Atlas
- Author
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Rozenblatt-Rosen, O., Shin, J. W., Rood, J. E., Hupalowska, A., Ardlie, K., Clatworthy, M., Carninci, P., Enard, W., Greenleaf, W., Heyn, H., Lein, E., Levin, J. Z., Linnarsson, S., Lundberg, Emma, Meyer, K., Navin, N., Nolan, G., Teichmann, S., Voet, T., Zhuang, X., Regev, A., Group, Human Cell Atlas Standards and Technology Working, Rozenblatt-Rosen, O., Shin, J. W., Rood, J. E., Hupalowska, A., Ardlie, K., Clatworthy, M., Carninci, P., Enard, W., Greenleaf, W., Heyn, H., Lein, E., Levin, J. Z., Linnarsson, S., Lundberg, Emma, Meyer, K., Navin, N., Nolan, G., Teichmann, S., Voet, T., Zhuang, X., Regev, A., and Group, Human Cell Atlas Standards and Technology Working
- Abstract
QC 20211116
- Published
- 2021
- Full Text
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19. 2238P Tebentafusp reprograms immunosuppressive tumor-associated M2 macrophages towards anti-tumoral M1 macrophages
- Author
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Piulats Rodriguez, J.M., Guc, E., Treveil, A., Nieto, P., Camera, A., Clubley, J., Heyn, H., Stanhope, S., Collins, L., Ranade, K., and Benlahrech, A.
- Published
- 2023
- Full Text
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20. Impaired DICER1 function promotes stemness and metastasis in colon cancer
- Author
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Iliou, M S, da Silva-Diz, V, Carmona, F J, Ramalho-Carvalho, J, Heyn, H, Villanueva, A, Muñoz, P, and Esteller, M
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- 2014
- Full Text
- View/download PDF
21. LifeTime and improving European healthcare through cell-based interceptive medicine
- Author
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Rajewsky, N. (Nikolaus), Almouzni, G. (Geneviève), Gorski, S.A. (Stanislaw A.), Aerts, S. (Stein), Amit, I. (Ido), Bertero, M.G. (Michela G.), Bock, C. (Christoph), Bredenoord, A.L. (Annelien L.), Cavalli, G. (Giacomo), Chiocca, S. (Susanna), Clevers, H.C. (Hans), Strooper, B. (Bart) de, Eggert, A. (Angelika), Ellenberg, J. (Jan), Fernández, X.M. (Xosé M.), Figlerowicz, M. (Marek), Gasser, S.M. (Susan M.), Hübner, N. (Norbert), Kjems, J. (Jørgen), Knoblich, J.A. (Jürgen A.), Krabbe, G. (Grietje), Lichter, P. (Peter), Linnarsson, S. (Sten), Marine, J.-C. (J.), Marioni, J. (John), Marti-Renom, M.A. (Marc A.), Netea, M.G. (Mihai), Nickel, D. (Dörthe), Nollmann, M. (Marcelo), Novak, H.R. (Halina R.), Parkinson, H. (Helen), Piccolo, S. (Stefano), Pinheiro, I. (Inês), Pombo, A. (Ana), Popp, C. (Christian), Reik, W. (Wolf), Roman-Roman, S. (Sergio), Rosenstiel, P. (Philip), Schultze, J.L. (Joachim), Stegle, O. (Oliver), Tanay, A. (Amos), Testa, G. (Giuseppe), Thanos, D. (Dimitris), Theis, F. (Fabian), Torres-Padilla, M.-E. (Maria-Elena), Valencia, A. (Alfonso), Vallot, C. (Céline), van Oudenaarden, A. (Alexander), Vidal, M. (Marie), Voet, T. (Thierry), Alberi, L. (Lavinia), Alexander, S. (Stephanie), Alexandrov, T. (Theodore), Arenas, E. (Ernest), Bagni, C. (Claudia), Balderas, R. (Robert), Bandelli, A. (Andrea), Becher, B. (Burkhard), Becker, M. (Matthias), Beerenwinkel, N. (Niko), Benkirame, M. (Monsef), Beyer, M. (Marc), Bickmore, W. (Wendy), Biessen, E.E.A.L. (Erik E.A.L.), Blomberg, N. (Niklas), Blumcke, I. (Ingmar), Bodenmiller, B. (Bernd), Borroni, B. (Barbara), Boumpas, D.T. (Dimitrios T.), Bourgeron, T. (Thomas), Bowers, S. (Sarion), Braeken, D. (Dries), Brooksbank, C. (Catherine), Brose, N. (Nils), Bruining, J. (Hans), Bury, J. (Jo), Caporale, N. (Nicolo), Cattoretti, G. (Giorgio), Chabane, N. (Nadia), Chneiweiss, H. (Hervé), Cook, S.A. (Stuart A.), Curatolo, P. (Paolo), Jonge, M.I. (Marien) de, Deplancke, B. (Bart), De Strooper, B. (Bart), de Witte, P. (Peter), Dimmeler, S. (Stefanie), Draganski, B. (Bogdan), Drews, A.-D. (Anna-Dorothee), Dumbrava, C. (Costica), Engelhardt, S. (Stefan), Gasser, T. (Thomas), Giamarellos-Bourboulis, E. (Evangelos), Graff, C. (Caroline), Grün, D. (Dominic), Gut, I. (Ivo), Hansson, O. (Oskar), Henshall, D.C. (David C.), Herland, A. (Anna), Heutink, P. (Peter), Heymans, S. (Stephane), Heyn, H. (Holger), Huch, M. (Meritxell), Huitinga, I. (Inge), Jackowiak, P. (Paulina), Jongsma, K.R. (Karin), Journot, L. (Laurent), Junker, J.P. (Jan Philipp), Katz, S. (Shauna), Kehren, J. (Jeanne), Kempa, S. (Stefan), Kirchhof, P. (Paulus), Klein, C. (Christoph), Koralewska, N. (Natalia), Korbel, J.O. (Jan), Kühnemund, M. (Malte), Lamond, A.I. (Angus I.), Lauwers, E. (Elsa), Le Ber, I. (Isabelle), Leinonen, V. (Ville), Tobon, A.L. (Alejandro Lopez), Lundberg, E. (Emma), Lunkes, A. (Astrid), Maatz, H. (Henrike), Mann, M. (Mathias), Marelli, L. (Luca), Matser, V. (Vera), Matthews, P.M. (P.), Mechta-Grigoriou, F. (Fatima), Menon, R. (Radhika), Nielsen, A.F. (Anne F.), Pagani, M. (Massimiliano), Pasterkamp, R.J. (Jeroen), Pitkanen, A. (Asla), Popescu, V. (Valentin), Pottier, C. (Cyril), Puisieux, A. (Alain), Rademakers, R. (Rosa), Reiling, D. (Dory), Reiner, O. (Orly), Remondini, D. (Daniel), Ritchie, C. (Craig), Rohrer, J.D. (Jonathan D.), Saliba, A.-E. (Antione-Emmanuel), Sánchez-Valle, R. (Raquel), Santosuosso, A. (Amedeo), Sauter, A. (Arnold), Scheltema, R.A. (Richard A.), Scheltens, P. (Philip), Schiller, H.B. (Herbert B.), Schneider, A. (Anja), Seibler, P. (Philip), Sheehan-Rooney, K. (Kelly), Shields, D. (David), Sleegers, K. (Kristel), Smit, G. (Guus), Smith, K.G.C. (Kenneth G. C.), Smolders, I. (Ilse), Synofzik, M. (Matthis), Tam, W.L. (Wai Long), Teichmann, S. (Sarah), Thom, M. (Maria), Turco, M.Y. (Margherita Y.), Beusekom, H.M.M. (Heleen) van, Vandenberghe, R. (Rik), den Hoecke, S.V. (Silvie Van), Van de Poel, E. (Ellen), der Ven, A. (Andre van), van der Zee, J. (Julie), van Lunzen, J. (Jan), van Minnebruggen, G. (Geert), Van Paesschen, W. (Wim), Swieten, J.C. (John) van, van Vught, R. (Remko), Verhage, M. (Matthijs), Verstreken, P. (Patrik), Villa, C.E. (Carlo Emanuele), Vogel, J. (Jörg), Kalle, C. (Christof) von, Walter, J. (Jörn), Weckhuysen, S. (Sarah), Weichert, W. (Wilko), Wood, L. (Louisa), Ziegler, A.-G. (Anette-Gabriele), Zipp, F. (Frauke), Rajewsky, N. (Nikolaus), Almouzni, G. (Geneviève), Gorski, S.A. (Stanislaw A.), Aerts, S. (Stein), Amit, I. (Ido), Bertero, M.G. (Michela G.), Bock, C. (Christoph), Bredenoord, A.L. (Annelien L.), Cavalli, G. (Giacomo), Chiocca, S. (Susanna), Clevers, H.C. (Hans), Strooper, B. (Bart) de, Eggert, A. (Angelika), Ellenberg, J. (Jan), Fernández, X.M. (Xosé M.), Figlerowicz, M. (Marek), Gasser, S.M. (Susan M.), Hübner, N. (Norbert), Kjems, J. (Jørgen), Knoblich, J.A. (Jürgen A.), Krabbe, G. (Grietje), Lichter, P. (Peter), Linnarsson, S. (Sten), Marine, J.-C. (J.), Marioni, J. (John), Marti-Renom, M.A. (Marc A.), Netea, M.G. (Mihai), Nickel, D. (Dörthe), Nollmann, M. (Marcelo), Novak, H.R. (Halina R.), Parkinson, H. (Helen), Piccolo, S. (Stefano), Pinheiro, I. (Inês), Pombo, A. (Ana), Popp, C. (Christian), Reik, W. (Wolf), Roman-Roman, S. (Sergio), Rosenstiel, P. (Philip), Schultze, J.L. (Joachim), Stegle, O. (Oliver), Tanay, A. (Amos), Testa, G. (Giuseppe), Thanos, D. (Dimitris), Theis, F. (Fabian), Torres-Padilla, M.-E. (Maria-Elena), Valencia, A. (Alfonso), Vallot, C. (Céline), van Oudenaarden, A. (Alexander), Vidal, M. (Marie), Voet, T. (Thierry), Alberi, L. (Lavinia), Alexander, S. (Stephanie), Alexandrov, T. (Theodore), Arenas, E. (Ernest), Bagni, C. (Claudia), Balderas, R. (Robert), Bandelli, A. (Andrea), Becher, B. (Burkhard), Becker, M. (Matthias), Beerenwinkel, N. (Niko), Benkirame, M. (Monsef), Beyer, M. (Marc), Bickmore, W. (Wendy), Biessen, E.E.A.L. (Erik E.A.L.), Blomberg, N. (Niklas), Blumcke, I. (Ingmar), Bodenmiller, B. (Bernd), Borroni, B. (Barbara), Boumpas, D.T. (Dimitrios T.), Bourgeron, T. (Thomas), Bowers, S. (Sarion), Braeken, D. (Dries), Brooksbank, C. (Catherine), Brose, N. (Nils), Bruining, J. (Hans), Bury, J. (Jo), Caporale, N. (Nicolo), Cattoretti, G. (Giorgio), Chabane, N. (Nadia), Chneiweiss, H. (Hervé), Cook, S.A. (Stuart A.), Curatolo, P. (Paolo), Jonge, M.I. (Marien) de, Deplancke, B. (Bart), De Strooper, B. (Bart), de Witte, P. (Peter), Dimmeler, S. (Stefanie), Draganski, B. (Bogdan), Drews, A.-D. (Anna-Dorothee), Dumbrava, C. (Costica), Engelhardt, S. (Stefan), Gasser, T. (Thomas), Giamarellos-Bourboulis, E. (Evangelos), Graff, C. (Caroline), Grün, D. (Dominic), Gut, I. (Ivo), Hansson, O. (Oskar), Henshall, D.C. (David C.), Herland, A. (Anna), Heutink, P. (Peter), Heymans, S. (Stephane), Heyn, H. (Holger), Huch, M. (Meritxell), Huitinga, I. (Inge), Jackowiak, P. (Paulina), Jongsma, K.R. (Karin), Journot, L. (Laurent), Junker, J.P. (Jan Philipp), Katz, S. (Shauna), Kehren, J. (Jeanne), Kempa, S. (Stefan), Kirchhof, P. (Paulus), Klein, C. (Christoph), Koralewska, N. (Natalia), Korbel, J.O. (Jan), Kühnemund, M. (Malte), Lamond, A.I. (Angus I.), Lauwers, E. (Elsa), Le Ber, I. (Isabelle), Leinonen, V. (Ville), Tobon, A.L. (Alejandro Lopez), Lundberg, E. (Emma), Lunkes, A. (Astrid), Maatz, H. (Henrike), Mann, M. (Mathias), Marelli, L. (Luca), Matser, V. (Vera), Matthews, P.M. (P.), Mechta-Grigoriou, F. (Fatima), Menon, R. (Radhika), Nielsen, A.F. (Anne F.), Pagani, M. (Massimiliano), Pasterkamp, R.J. (Jeroen), Pitkanen, A. (Asla), Popescu, V. (Valentin), Pottier, C. (Cyril), Puisieux, A. (Alain), Rademakers, R. (Rosa), Reiling, D. (Dory), Reiner, O. (Orly), Remondini, D. (Daniel), Ritchie, C. (Craig), Rohrer, J.D. (Jonathan D.), Saliba, A.-E. (Antione-Emmanuel), Sánchez-Valle, R. (Raquel), Santosuosso, A. (Amedeo), Sauter, A. (Arnold), Scheltema, R.A. (Richard A.), Scheltens, P. (Philip), Schiller, H.B. (Herbert B.), Schneider, A. (Anja), Seibler, P. (Philip), Sheehan-Rooney, K. (Kelly), Shields, D. (David), Sleegers, K. (Kristel), Smit, G. (Guus), Smith, K.G.C. (Kenneth G. C.), Smolders, I. (Ilse), Synofzik, M. (Matthis), Tam, W.L. (Wai Long), Teichmann, S. (Sarah), Thom, M. (Maria), Turco, M.Y. (Margherita Y.), Beusekom, H.M.M. (Heleen) van, Vandenberghe, R. (Rik), den Hoecke, S.V. (Silvie Van), Van de Poel, E. (Ellen), der Ven, A. (Andre van), van der Zee, J. (Julie), van Lunzen, J. (Jan), van Minnebruggen, G. (Geert), Van Paesschen, W. (Wim), Swieten, J.C. (John) van, van Vught, R. (Remko), Verhage, M. (Matthijs), Verstreken, P. (Patrik), Villa, C.E. (Carlo Emanuele), Vogel, J. (Jörg), Kalle, C. (Christof) von, Walter, J. (Jörn), Weckhuysen, S. (Sarah), Weichert, W. (Wilko), Wood, L. (Louisa), Ziegler, A.-G. (Anette-Gabriele), and Zipp, F. (Frauke)
- Abstract
LifeTime aims to track, understand and target human cells during the onset and progression of complex diseases and their response to therapy at single-cell resolution. This mission will be implemented through the development and integration of single-cell multi-omics and imaging, artificial intelligence and patient-derived experimental disease models during progression from health to disease. Analysis of such large molecular and clinical datasets will discover molecular mechanisms, create predictive computational models of disease progression, and reveal new drug targets and therapies. Timely detection and interception of disease embedded in an ethical and patient-centered vision will be achieved through interactions across academia, hospitals, patient-associations, health data management systems and industry. Applying this strategy to key medical challenges in cancer, neurological, infectious, chronic inflammatory and cardiovascular diseases at the single-cell level will usher in cell-based interceptive medicine in Europe over the next decade.
- Published
- 2020
- Full Text
- View/download PDF
22. Benchmarking single-cell RNA-sequencing protocols for cell atlas projects
- Author
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Mereu, E, Lafzi, A, Moutinho, C, Ziegenhain, C, McCarthy, DJ, Alvarez-Varela, A, Batlle, E, Sagar, Gruen, D, Lau, JK, Boutet, SC, Sanada, C, Ooi, A, Jones, RC, Kaihara, K, Brampton, C, Talaga, Y, Sasagawa, Y, Tanaka, K, Hayashi, T, Braeuning, C, Fischer, C, Sauers, S, Trefzer, T, Conrad, C, Adiconis, X, Nguyen, LT, Regev, A, Levin, JZ, Parekh, S, Janjic, A, Wange, LE, Bagnoli, JW, Enard, W, Gut, M, Sandberg, R, Nikaido, I, Gut, I, Stegle, O, Heyn, H, Mereu, E, Lafzi, A, Moutinho, C, Ziegenhain, C, McCarthy, DJ, Alvarez-Varela, A, Batlle, E, Sagar, Gruen, D, Lau, JK, Boutet, SC, Sanada, C, Ooi, A, Jones, RC, Kaihara, K, Brampton, C, Talaga, Y, Sasagawa, Y, Tanaka, K, Hayashi, T, Braeuning, C, Fischer, C, Sauers, S, Trefzer, T, Conrad, C, Adiconis, X, Nguyen, LT, Regev, A, Levin, JZ, Parekh, S, Janjic, A, Wange, LE, Bagnoli, JW, Enard, W, Gut, M, Sandberg, R, Nikaido, I, Gut, I, Stegle, O, and Heyn, H
- Abstract
Single-cell RNA sequencing (scRNA-seq) is the leading technique for characterizing the transcriptomes of individual cells in a sample. The latest protocols are scalable to thousands of cells and are being used to compile cell atlases of tissues, organs and organisms. However, the protocols differ substantially with respect to their RNA capture efficiency, bias, scale and costs, and their relative advantages for different applications are unclear. In the present study, we generated benchmark datasets to systematically evaluate protocols in terms of their power to comprehensively describe cell types and states. We performed a multicenter study comparing 13 commonly used scRNA-seq and single-nucleus RNA-seq protocols applied to a heterogeneous reference sample resource. Comparative analysis revealed marked differences in protocol performance. The protocols differed in library complexity and their ability to detect cell-type markers, impacting their predictive value and suitability for integration into reference cell atlases. These results provide guidance both for individual researchers and for consortium projects such as the Human Cell Atlas.
- Published
- 2020
23. Erratum: DNMT3A mutations mediate the epigenetic reactivation of the leukemogenic factor MEIS1 in acute myeloid leukemia
- Author
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Ferreira, H J, Heyn, H, Vizoso, M, Moutinho, C, Vidal, E, Gomez, A, Martínez-Cardús, A, Simó-Riudalbas, L, Moran, S, Jost, E, and Esteller, M
- Published
- 2017
- Full Text
- View/download PDF
24. Machine Learning Identifies Stemness Features Associated with Oncogenic Dedifferentiation
- Author
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Stuart, J.M., Huelsken, J., Czerwi��ska, P., Kami��ska, B., Mishra, L., Godwin, A.K., Mazurek, S., Noushmehr, H., Wiznerowicz, M., Lazar, A.J., Sokolov, A., The Cancer Genome Atlas Research Network, Krasnitz, A., Laird, P.W., Gentles, A.J., Hoadley, K.A., Burzykowski, T., Omberg, L., Gevaert, O., Malta, T.M., Weinstein, J.N., Heyn, H., Colaprico, A., and Poisson, L.
- Subjects
cancer stem cells ,Carcinogenesis ,pan-cancer ,The Cancer Genome Atlas ,Cancer Genome Atlas Research Network ,epigenomic ,Medical and Health Sciences ,Machine Learning ,genomic ,Databases ,stemness ,Genetic ,Stem Cell Research - Nonembryonic - Human ,Neoplasms ,Tumor Microenvironment ,Humans ,Neoplasm Metastasis ,Cancer ,Stem Cells ,dedifferentiation ,DNA Methylation ,Cell Dedifferentiation ,Biological Sciences ,Stem Cell Research ,MicroRNAs ,Good Health and Well Being ,Stem Cell Research - Nonembryonic - Non-Human ,Transcriptome ,Epigenesis ,Developmental Biology - Abstract
Cancer progression involves the gradual loss of a differentiated phenotype and acquisition of progenitor and stem-cell-like features. Here, we provide novel stemness indices for assessing the degree of oncogenic dedifferentiation. We used an innovative one-class logistic regression (OCLR) machine-learning algorithm to extract transcriptomic and epigenetic feature sets derived from non-transformed pluripotent stem cells and their differentiated progeny. Using OCLR, we were able to identify previously undiscovered biological mechanisms associated with the dedifferentiated oncogenic state. Analyses of the tumor microenvironment revealed unanticipated correlation of cancer stemness with immune checkpoint expression and infiltrating immune cells. We found that the dedifferentiated oncogenic phenotype was generally most prominent in metastatic tumors. Application of our stemness indices to single-cell data revealed patterns of intra-tumor molecular heterogeneity. Finally, the indices allowed for the identification of novel targets and possible targeted therapies aimed at tumor differentiation. Stemness features extracted from transcriptomic and epigenetic data from TCGA tumors reveal novel biological and clinical insight, as well as potential drug targets for anti-cancer therapies.
- Published
- 2018
25. PM20D1 is a quantitative trait locus associated with Alzheimer's disease
- Author
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Sanchez-Mut JV, Heyn H, Silva BA, Dixsaut L, Garcia-Esparcia P, Vidal E, Sayols S, Glauser L, Monteagudo-Sánchez A, Perez-Tur J, Ferrer I, Monk D, Schneider B, Esteller M, and Gräff J
- Abstract
The chances to develop Alzheimer's disease (AD) result from a combination of genetic and non-genetic risk factors 1 , the latter likely being mediated by epigenetic mechanisms 2 . In the past, genome-wide association studies (GWAS) have identified an important number of risk loci associated with AD pathology 3 , but a causal relationship remains difficult to establish. In contrast, locus-specific or epigenome-wide association studies (EWAS) have revealed site-specific epigenetic alterations, which provide mechanistic insights for a particular risk gene but often lack the statistical power of GWAS 4 . Here, combining both approaches, we report a previously unidentified association of the peptidase M20-domain-containing protein 1 (PM20D1) with AD. We find that PM20D1 is a methylation and expression quantitative trait locus coupled to an AD-risk associated haplotype, which displays enhancer-like characteristics and contacts the PM20D1 promoter via a haplotype-dependent, CCCTC-binding-factor-mediated chromatin loop. Furthermore, PM20D1 is increased following AD-related neurotoxic insults at symptomatic stages in the APP/PS1 mouse model of AD and in human patients with AD who are carriers of the non-risk haplotype. In line, genetically increasing or decreasing the expression of PM20D1 reduces and aggravates AD-related pathologies, respectively. These findings suggest that in a particular genetic background, PM20D1 contributes to neuroprotection against AD.
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- 2018
26. A DNA methylation map of human cancer at single base-pair resolution
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Vidal, E, primary, Sayols, S, additional, Moran, S, additional, Guillaumet-Adkins, A, additional, Schroeder, M P, additional, Royo, R, additional, Orozco, M, additional, Gut, M, additional, Gut, I, additional, Lopez-Bigas, N, additional, Heyn, H, additional, and Esteller, M, additional
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- 2017
- Full Text
- View/download PDF
27. Epigenetic loss of the RNA decapping enzyme NUDT16 mediates C-MYC activation in T-cell acute lymphoblastic leukemia
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Anadón, C, primary, van Tetering, G, additional, Ferreira, H J, additional, Moutinho, C, additional, Martínez-Cardús, A, additional, Villanueva, A, additional, Soler, M, additional, Heyn, H, additional, Moran, S, additional, Castro de Moura, M, additional, Setien, F, additional, Vidal, A, additional, Genescà, E, additional, Ribera, J M, additional, Nomdedeu, J F, additional, Guil, S, additional, and Esteller, M, additional
- Published
- 2017
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28. Assessing Associations between the AURKA-HMMR-TPX2-TUBG1 Functional Module and Breast Cancer Risk in BRCA1/2 Mutation Carriers
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Blanco, I., Kuchenbaecker, K., Cuadras, D., Wang, X.S., Barrowdale, D., Garibay, G.R., Librado, P., Sanchez-Gracia, A., Rozas, J., Bonifaci, N., McGuffog, L., Pankratz, V.S., Islam, A., Mateo, F., Berenguer, A., Petit, A., Catala, I., Brunet, J., Feliubadalo, L., Tornero, E., Benitez, J., Osorio, A., Cajal, T.R.Y., Nevanlinna, H., Aittomaki, K., Arun, B.K., Toland, A.E., Karlan, B.Y., Walsh, C., Lester, J., Greene, M.H., Mai, P.L., Nussbaum, R.L., Andrulis, I.L., Domchek, S.M., Nathanson, K.L., Rebbeck, T.R., Barkardottir, R.B., Jakubowska, A., Lubinski, J., Durda, K., Jaworska-Bieniek, K., Claes, K., Maerken, T. van, Diez, O., Hansen, T.V., Jonson, L., Gerdes, A.M., Ejlertsen, B., Hoya, M. de la, Caldees, T., Dunning, A.M., Oliver, C., Fineberg, E., Cook, M., Peock, S., McCann, E., Murray, A., Jacobs, C., Pichert, G., Lalloo, F., Chu, C., Dorkins, H., Paterson, J., Ong, K.R., Teixeira, M.R., Teixeira, Hogervorst, F.B.L., Hout, A.H. van der, Seynaeve, C., Luijt, R.B. van der, Ligtenberg, M.J.L., Devilee, P., Wijnen, J.T., Rookus, M.A., Meijers-Heijboer, H.E.J., Blok, M.J., Ouweland, A.M.W. van den, Aalfs, C.M., Rodriguez, G.C., Phillips, K.A.A., Piedmonte, M., Nerenstone, S.R., Bae-Jump, V.L., O'Malley, D.M., Ratner, E.S., Schmutzler, R.K., Wappenschmidt, B., Rhiem, K., Engel, C., Meindl, A., Ditsch, N., Arnold, N., Plendl, H.J., Niederacher, D., Sutter, C., Wang-Gohrke, S., Steinemann, D., Preisler-Adams, S., Kast, K., Varon-Mateeva, R., Gehrig, A., Bojesen, A., Pedersen, I.S., Sunde, L., Jensen, U.B., Thomassen, M., Kruse, T.A., Foretova, L., Peterlongo, P., Bernard, L., Peissel, B., Scuvera, G., Manoukian, S., Radice, P., Ottini, L., Montagna, M., Agata, S., Maugard, C., Simard, J., Soucy, P., Berger, A., Fink-Retter, A., Singer, C.F., Rappaport, C., Geschwantler-Kaulich, D., Tea, M.K., Pfeiler, G., John, E.M., Miron, A., Neuhausen, S.L., Terry, M.B., Chung, W.K., Daly, M.B., Goldgar, D.E., Janavicius, R., Dorfling, C.M., Rensburg, E.J. van, Fostira, F., Konstantopoulou, I., Garber, J., Godwin, A.K., Olah, E., Narod, S.A., Rennert, G., Paluch, S.S., Laitman, Y., Friedman, E., Liljegren, A., Rantala, J., Stenmark-Askmalm, M., Loman, N., Imyanitov, E.N., Hamann, U., Spurdle, A.B., Healey, S., Weitzel, J.N., Herzog, J., Margileth, D., Gorrini, C., Esteller, M., Gomez, A., Sayols, S., Vidal, E., Heyn, H., Stoppa-Lyonnet, Leone, M., Barjhoux, L., Fassy-Colcombet, M., Pauw, A. de, Lasset, C., Ferrer, S.F., Castera, L., Berthet, P., Cornelis, F., Bignon, Y.J., Damiola, F., Mazoyer, S., Sinilnikova, O.M., Maxwell, C.A., Vijai, J., Robson, M., Kauff, N., Corines, M.J., Villano, D., Cunningham, J., Lee, A., Lindor, N., Lazaro, C., Easton, D.F., Offit, K., Chenevix-Trench, G., Couch, F.J., Antoniou, A.C., Pujana, M.A., BCFR, SWE-BRCA, KConFab Investigators, GEMO, Human genetics, CCA - Oncogenesis, Medical Oncology, Clinical Genetics, Suzuki, Hiromu, MUMC+: DA KG Lab Centraal Lab (9), RS: GROW - Oncology, RS: GROW - R4 - Reproductive and Perinatal Medicine, CCA -Cancer Center Amsterdam, ARD - Amsterdam Reproduction and Development, Human Genetics, Department of Obstetrics and Gynecology, Clinicum, Medicum, Haartman Institute (-2014), and Department of Medical and Clinical Genetics
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single nucleotide ,Oncology ,Carcinogenesis ,TUBG1 ,Genes, BRCA2 ,Genes, BRCA1 ,Càncer d'ovari ,MODIFIERS ,Genome-wide association study ,Cell Cycle Proteins ,Breast cancer ,mammary glands ,Aetiology ,genes ,skin and connective tissue diseases ,Cancer ,Extracellular Matrix Proteins ,Hazard ratio ,CHIP-SEQ ,3. Good health ,ddc ,Hyaluronan Receptors ,Medicine ,Teixeira ,Human ,medicine.medical_specialty ,Evolution ,Science ,Non-P.H.S ,Single-nucleotide polymorphism ,Evolution, Molecular ,SDG 3 - Good Health and Well-being ,Ovarian cancer ,Genetics ,biochemistry ,Humans ,human ,CELL ,Polymorphism ,GENOME-WIDE ASSOCIATION ,medicine (all) ,Retrospective Studies ,Cancer och onkologi ,Prevention ,Mutació (Biologia) ,Biology and Life Sciences ,Molecular ,SWE-BRCA ,BRCA1 ,medicine.disease ,BRCA2 ,POLYMORPHISM ,Genes ,Genetic Loci ,Cancer and Oncology ,Mutation ,U.S. Gov't ,Bioinformatics ,medicine.disease_cause ,3123 Gynaecology and paediatrics ,Tubulin ,Tumours of the digestive tract Radboud Institute for Molecular Life Sciences [Radboudumc 14] ,ELEMENTS ,2.1 Biological and endogenous factors ,CD44 ,Non-U.S. Gov't ,Aurora Kinase A ,Likelihood Functions ,Multidisciplinary ,Research Support, Non-U.S. Gov't ,agricultural and biological sciences (all) ,genetics and molecular biology (all) ,BCFR ,Nuclear Proteins ,Single Nucleotide ,Mammary Glands ,SURVIVAL ,kConFab Investigators ,Female ,Microtubule-Associated Proteins ,Research Article ,Antigens, CD44 ,aurora kinase A ,breast neoplasms ,carcinogenesis ,cell cycle proteins ,estrogen receptor alpha ,evolution, molecular ,extracellular matrix proteins ,female ,genetic loci ,genetic predisposition to disease ,humans ,likelihood functions ,mammary glands, human ,microtubule-associated proteins ,nuclear proteins ,polymorphism ,retrospective studies ,tubulin ,genes, BRCA1 ,genes, BRCA2 ,mutation ,biochemistry, genetics and molecular biology (all) ,SUSCEPTIBILITY LOCI ,General Science & Technology ,3122 Cancers ,Breast Neoplasms ,Biology ,Research Support ,Polymorphism, Single Nucleotide ,N.I.H ,GENETIC INTERACTION NETWORKS ,Càncer de mama ,EXPRESSION SIGNATURE ,Amino acid sequence ,Research Support, N.I.H., Extramural ,Internal medicine ,Seqüència d'aminoàcids ,evolution ,Genetic variation ,Journal Article ,medicine ,Genetic Predisposition to Disease ,ddc:610 ,molecular ,Antigens ,Mammary Glands, Human ,ddc:611 ,Intramural ,Estrogen Receptor alpha ,Extramural ,Mutation (Biology) ,Research Support, N.I.H., Intramural ,3111 Biomedicine ,GEMO ,Research Support, U.S. Gov't, Non-P.H.S - Abstract
While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood approach. The association of HMMR rs299290 with breast cancer risk in BRCA1 mutation carriers was confirmed: per-allele hazard ratio (HR) = 1.10, 95% confidence interval (CI) 1.04 - 1.15, p = 1.9 x 10(-4) (false discovery rate (FDR)-adjusted p = 0.043). Variation in CSTF1, located next to AURKA, was also found to be associated with breast cancer risk in BRCA2 mutation carriers: rs2426618 per-allele HR = 1.10, 95% CI 1.03 - 1.16, p = 0.005 (FDR-adjusted p = 0.045). Assessment of pairwise interactions provided suggestions (FDR-adjusted p(interaction) values greater than 0.05) for deviations from the multiplicative model for rs299290 and CSTF1 rs6064391, and rs299290 and TUBG1 rs11649877 in both BRCA1 and BRCA2 mutation carriers. Following these suggestions, the expression of HMMR and AURKA or TUBG1 in sporadic breast tumors was found to potentially interact, influencing patients survival. Together, the results of this study support the hypothesis of a causative link between altered function of AURKA-HMMR-TPX2-TUBG1 and breast carcinogenesis in BRCA1/2 mutation carriers. Funding Agencies|National Cancer Institute [UM1 CA164920]; Lithuania (BFBOCC-LT): Research Council of Lithuania grant [LIG-07/2012]; Hereditary Cancer Association (Paveldimo vezio asociacija); LSC grant [10.0010.08]; ESF [2009/0220/1DP/1.1.1.2.0/09/APIA/VIAA/016]; Liepajas municipal council; Cancer Association of South Africa (CANSA); Morris and Horowitz Familes Endowed Professorship; NEYE Foundation; Spanish Association against Cancer [AECC08, RTICC 06/0020/1060, FISPI08/1120]; Mutua Madrilena Foundation (FMMA); COH-CCGCRN: City of Hope Clinical Cancer Genetics Community Network from the National Cancer Institute and the Office of the Director, National Institutes of Health; Hereditary Cancer Research Registry from the National Cancer Institute and the Office of the Director, National Institutes of Health [RC4CA153828]; Fondazione IRCCS Istituto Nazionale Tumori; Cancer Research-United Kingdom grant [C12292/A11174, C1287/ A10118]; NHMRC Program Grant; DKFZ; European Union (European Social Fund-ESF); Greek national funds through the Operational Program "Education and Lifelong Learning" of the National Strategic Reference Framework (NSRF)-Research Funding Program of the General Secretariat for Research and Technology: ARISTEIA; European Social Fund; Cancer Research United Kingdom Grants [C1287/A10118, C1287/A11990]; National Institute of Health Research (NIHR) grant; NIHR grant; Royal Marsden NHS Foundation Trust; Cancer Research United Kingdom Grant [C5047/A8385]; University of Kansas Cancer Center [P30 CA168524]; Kansas Bioscience Authority Eminent Scholar Program; Chancellors Distinguished Chair in Biomedical Sciences Professorship; AKG [5U01CA113916, R01CA140323]; German Cancer Aid [109076]; Center for Molecular Medicine Cologne (CMMC); Ligue National Contre le Cancer; Association "Le cancer du sein, parlonsen!" Award; Canadian Institutes of Health Research; Fund for Scientific Research Flanders (FWO); National Cancer Institute grant [CA 27469]; GOG Statistical and Data Center [CA 37517]; GOGs Cancer Prevention and Control Committee [CA 101165]; Intramural Research Program, NCI; ISCIII (Spain) [RD12/00369/0006, 12/00539]; European Regional Development FEDER funds; Helsinki University Central Hospital Research Fund; Academy of Finland [132473]; Finnish Cancer Society; Sigrid Juselius Foundation; Dutch Cancer Society grant [NKI1998-1854, NKI2004-3088, NKI2007-3756]; Netherlands Organization of Scientific Research [NWO 91109024]; Pink Ribbon grant [110005]; BBMRI grant [NWO 184.021.007/CP46]; Hungarian Research Grant [KTIA-OTKA CK-80745]; Norwegian EEA Financial Mechanism [HU0115/NA/2008-3/OP-9]; Spanish Ministry of Health ISCIII FIS [PI10/01422, PI12/01528, PI13/00285]; RTICC [RD12/0036/0008]; Ramon Areces (XV) Foundation; Eugenio Rodriguez Pascual Foundation; Roses Contra el Cancer Foundation; Spanish Association Against Cancer (AECC); AGAUR Generalitat de Catalunya [2009-SGR290, 2009-SGR293]; Polish Foundation of Science; Icelandic Association "Walking for Breast Cancer Research"; Nordic Cancer Union; Landspitali University Hospital Research Fund; Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program; Canadian Breast Cancer Research Alliance-grant [019511]; Ministry of Economic Development, Innovation and Export Trade-grant [PSR-SIIRI-701]; Ministero dellIstruzione, dellUniversita e della Ricerca and Ministero della Salute; Liga Portuguesa Contra o Cancro; National Breast Cancer Foundation; National Health and Medical Research Council (NHMRC); Queensland Cancer Fund; Cancer Council of New South Wales; Cancer Council of Victoria; Cancer Foundation of Western Australia; Cancer Councils of Tasmania; National Institutes of Health grant [CA128978]; NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201]; United States Department of Defence Ovarian Cancer Idea award [W81XWH-10-1-0341]; Breast Cancer Research Foundation; Jewish General Hospital Weekend; Quebec Ministry of Economic Development, Innovation and Export Trade; Cancer Councils of South Australia; European Regional Development Fund; State Budget of the Czech Republic (RECAMO) [CZ.1.05/2.1.00/03.0101]; MH CZ-DRO (MMCI) [00209805]; Niehaus Family Genetics Research Fund; STARR Cancer Consortium Grant; NAROD [1R01 CA149429-01]; NCI Intramural Research Program, National Institutes of Health [NO2-CP-11019-50, N02-CP-65504]; Westat, Inc, Rockville, Maryland; Clalit Health Services in Israel; Israel Cancer Association; Breast Cancer Research Foundation (BCRF), New York; Russian Federation for Basic Research [11-04-00227, 12-04-00928, 12-04-01490]; Federal Agency for Science and Innovations, Russia [02.740.11.0780]; Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" program and grant from the National Cancer Institute [UM1 CA164920]; Breast Cancer Family Registry (BCFR); United States Government or the BCFR; Ohio State University Comprehensive Cancer Center; Isreal cancer association; Israeli Inherited breast cancer consortium; Swedish Cancer Society; Ralph and Marion Falk Medical Research Trust; Entertainment Industry Fund National Womens Cancer Research Alliance; National Institutes of Health (NIH) [R01-CA102776, R01-CA083855]; Rooney Family Foundation; Susan G. Komen Foundation for the cure, Basser Research Center; American Cancer Society Early Detection Professorship [SIOP-06-258-01-COUN]; SAF2010-20493; [PBZ_KBN_122/P05/2004]
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- 2015
29. Collaborative Knowledge Acquisition and Explorationin Technology Search
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Stange, D., Andreas Nürnberger, and Heyn, H.
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gemeinsamer Wissenserwerb ,collaborative knowledge acquisition ,ddc:330 - Abstract
This article is about technology search as an example of a knowledge acquisition task in industry. Technology search is about finding technology related information in structured as well as unstructured sources. This information is needed to support optimal decision making in business processes. There are new opptortunities for technology search and challenges that need to be addressed. This article outlines some of these challenges and presents two concepts to address them in a search system.
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- 2015
30. Assessing associations between the AURKAHMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers
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Blanco, I. (Ignacio), Kuchenbaecker, K.B. (Karoline), Cuadras, D. (Daniel), Wang, X. (Xing), Barrowdale, D. (Daniel), De Garibay, G.R. (Gorka Ruiz), Librado, P. (Pablo), Sánchez-Gracia, A. (Alejandro), Rozas, J. (Julio), Bonifaci, N. (Núria), McGuffog, L. (Lesley), Pankratz, V.S. (Shane), Islam, A.B.M.M.K. (Abul), Mateo, F. (Francesca), Berenguer, A. (Antonio), Petit, A. (Anna), Català, I. (Isabel), Brunet, J. (Joan), Feliubadaló, L. (L.), Tornero, E. (Eva), Benítez, J. (Javier), Osorio, A. (Ana), Teresa, R. (Ramón), Teresa, C. (Cajal), Nevanlinna, H. (Heli), Aittomäki, K. (Kristiina), Arun, B.K. (Banu), Toland, A.E. (Amanda), Karlan, B.Y. (Beth), Walsh, C.S. (Christine), Lester, K.J. (Kathryn), Greene, M.H. (Mark), Mai, P.L. (Phuong), Nussbaum, R.L. (Robert L.), Andrulis, I.L. (Irene), Domchek, S.M. (Susan), Nathanson, K.L. (Katherine), Rebbeck, R. (Timothy), Barkardottir, R.B. (Rosa), Jakubowska, A. (Anna), Lubinski, J. (Jan), Durda, K. (Katarzyna), Jaworska-Bieniek, K. (Katarzyna), Claes, K. (Kathleen), Van Maerken, T. (Tom), Díez, O. (Orland), Hansen, T.V.O. (Thomas), Jønson, L. (Lars), Gerdes, A.-M. (Anne-Marie), Ejlertsen, B. (Bent), Hoya, M. (Miguel) de La, Caldes, T. (Trinidad), Dunning, A.M. (Alison), Oliver, C.T. (Clare), Fineberg, E. (Elena), Cook, M. (Margaret), Peock, S. (Susan), McCann, E. (Emma), Murray, A. (Alexandra), Jacobs, C. (Chris), Pichert, G. (Gabriella), Lalloo, F. (Fiona), Chu, C. (Carol), Dorkins, H. (Huw), Paterson, J. (Joan), Ong, K.-R. (Kai-Ren), Teixeira, M.R. (Manuel R.), Teixeira, T. (T.), Hogervorst, F.B.L. (Frans), Hout, A.H. (Annemarie) van der, Seynaeve, C.M. (Caroline), Van Der Luijt, R.B. (Rob B.), Ligtenberg, M.J. (Marjolijn), Devilee, P. (Peter), Wijnen, J.T. (Juul), Rookus, M.A. (Matti), Meijers-Heijboer, E.J. (Hanne), Blok, M.J. (Marinus), Ouweland, A.M.W. (Ans) van den, Aalfs, C.M. (Cora), Rodriguez, G.C. (Gustavo C.), Phillips, K.-A. (Kelly-Anne), Piedmonte, M. (Marion), Nerenstone, S. (Stacy), Bae-Jump, V.L. (Victoria L.), O'Malley, D.M. (David M.), Ratner, E.S. (Elena S.), Schmutzler, R.K. (Rita), Wapenschmidt, B. (Barbara), Rhiem, K. (Kerstin), Engel, C. (Christoph), Meindl, A. (Alfons), Ditsch, N. (Nina), Arnold, N. (Norbert), Plendl, H. (Hansjoerg), Niederacher, D. (Dieter), Sutter, C. (Christian), Wang-Gohrke, S. (Shan), Steinemann, D. (Doris), Preisler-Adams, S. (Sabine), Kast, K. (Karin), Varon-Mateeva, R. (Raymonda), Gehrig, P.A. (Paola A.), Bojesen, A. (Anders), Pedersen, I.S. (Inge Sokilde), Sunde, L. (Lone), Jensen, U.B., Thomassen, M. (Mads), Kruse, T.A. (Torben), Foretova, L. (Lenka), Peterlongo, P. (Paolo), Bernard, L. (Loris), Peissel, B. (Bernard), Scuvera, G. (Giulietta), Manoukian, S. (Siranoush), Radice, P. (Paolo), Ottini, L. (Laura), Montagna, M. (Marco), Agata, S. (Simona), Maugard, C., Simard, J. (Jacques), Soucy, P. (Penny), Berger, A. (Annemarie), Fink-Retter, A. (Anneliese), Singer, C.F. (Christian), Rappaport, C. (Christine), Geschwantler Kaulich, D. (Daphne), Tea, M.-K., Pfeiler, G. (Georg), John, E.M. (Esther), Miron, A. (Alexander), Neuhausen, S.L. (Susan), Terry, M.B. (Mary Beth), Chung, W.K. (Wendy K.), Daly, M.B. (Mary), Goldgar, D. (David), Janavicius, R. (Ramunas), Dorfling, C.M. (Cecilia), Rensburg, E.J. (Elizabeth) van, Fostira, F. (Florentia), Konstantopoulou, I. (I.), Garber, J., Godwin, A.K. (Andrew), Olah, E., Narod, S.A. (Steven A.), Rennert, G. (Gad), Paluch, S.S. (Shani), Laitman, Y. (Yael), Friedman, E. (Eitan), Liljegren, A. (Annelie), Rantala, J. (Johanna), Stenmark-Askmalm, M. (Marie), Loman, N. (Niklas), Imyanitov, E.N. (Evgeny), Hamann, U. (Ute), Spurdle, A.B. (Amanda), Healey, S. (Sue), Weitzel, J.N. (Jeffrey), Herzog, J. (Josef), Margileth, D. (David), Gorrini, C. (Chiara), Esteller, M. (Manel), Gómez, A. (Antonio), Sayols, S. (Sergi), Vidal, E. (Enrique), Heyn, H. (Holger), Stoppa-Lyonnet, D. (Dominique), Léone, M. (Mélanie), Barjhoux, L. (Laure), Fassy-Colcombet, M. (Marion), Pauw, A. (Antoine) de, Lasset, C. (Christine), Ferrer, S.F., Castera, L. (Laurent), Berthet, P. (Pascaline), Cornelis, F. (Franco̧is), Bignon, Y.-J. (Yves-Jean), Damiola, F. (Francesca), Mazoyer, S. (Sylvie), Sinilnikova, O. (Olga), Maxwell, C.A. (Christopher), Vijai, J. (Joseph), Robson, M. (Mark), Kauff, N. (Noah), Corines, M.J. (Marina J.), Villano, D. (Danylko), Cunningham, J.M. (Julie), Lee, A. (Adam), Lindor, N.M. (Noralane), Lázaro, C. (Conxi), Easton, D.F. (Douglas), Offit, K. (Kenneth), Chenevix-Trench, G. (Georgia), Couch, F.J. (Fergus), Antoniou, A.C. (Antonis C.), Pujana, M.A. (Miguel), Blanco, I. (Ignacio), Kuchenbaecker, K.B. (Karoline), Cuadras, D. (Daniel), Wang, X. (Xing), Barrowdale, D. (Daniel), De Garibay, G.R. (Gorka Ruiz), Librado, P. (Pablo), Sánchez-Gracia, A. (Alejandro), Rozas, J. (Julio), Bonifaci, N. (Núria), McGuffog, L. (Lesley), Pankratz, V.S. (Shane), Islam, A.B.M.M.K. (Abul), Mateo, F. (Francesca), Berenguer, A. (Antonio), Petit, A. (Anna), Català, I. (Isabel), Brunet, J. (Joan), Feliubadaló, L. (L.), Tornero, E. (Eva), Benítez, J. (Javier), Osorio, A. (Ana), Teresa, R. (Ramón), Teresa, C. (Cajal), Nevanlinna, H. (Heli), Aittomäki, K. (Kristiina), Arun, B.K. (Banu), Toland, A.E. (Amanda), Karlan, B.Y. (Beth), Walsh, C.S. (Christine), Lester, K.J. (Kathryn), Greene, M.H. (Mark), Mai, P.L. (Phuong), Nussbaum, R.L. (Robert L.), Andrulis, I.L. (Irene), Domchek, S.M. (Susan), Nathanson, K.L. (Katherine), Rebbeck, R. (Timothy), Barkardottir, R.B. (Rosa), Jakubowska, A. (Anna), Lubinski, J. (Jan), Durda, K. (Katarzyna), Jaworska-Bieniek, K. (Katarzyna), Claes, K. (Kathleen), Van Maerken, T. (Tom), Díez, O. (Orland), Hansen, T.V.O. (Thomas), Jønson, L. (Lars), Gerdes, A.-M. (Anne-Marie), Ejlertsen, B. (Bent), Hoya, M. (Miguel) de La, Caldes, T. (Trinidad), Dunning, A.M. (Alison), Oliver, C.T. (Clare), Fineberg, E. (Elena), Cook, M. (Margaret), Peock, S. (Susan), McCann, E. (Emma), Murray, A. (Alexandra), Jacobs, C. (Chris), Pichert, G. (Gabriella), Lalloo, F. (Fiona), Chu, C. (Carol), Dorkins, H. (Huw), Paterson, J. (Joan), Ong, K.-R. (Kai-Ren), Teixeira, M.R. (Manuel R.), Teixeira, T. (T.), Hogervorst, F.B.L. (Frans), Hout, A.H. (Annemarie) van der, Seynaeve, C.M. (Caroline), Van Der Luijt, R.B. (Rob B.), Ligtenberg, M.J. (Marjolijn), Devilee, P. (Peter), Wijnen, J.T. (Juul), Rookus, M.A. (Matti), Meijers-Heijboer, E.J. (Hanne), Blok, M.J. (Marinus), Ouweland, A.M.W. (Ans) van den, Aalfs, C.M. (Cora), Rodriguez, G.C. (Gustavo C.), Phillips, K.-A. (Kelly-Anne), Piedmonte, M. (Marion), Nerenstone, S. (Stacy), Bae-Jump, V.L. (Victoria L.), O'Malley, D.M. (David M.), Ratner, E.S. (Elena S.), Schmutzler, R.K. (Rita), Wapenschmidt, B. (Barbara), Rhiem, K. (Kerstin), Engel, C. (Christoph), Meindl, A. (Alfons), Ditsch, N. (Nina), Arnold, N. (Norbert), Plendl, H. (Hansjoerg), Niederacher, D. (Dieter), Sutter, C. (Christian), Wang-Gohrke, S. (Shan), Steinemann, D. (Doris), Preisler-Adams, S. (Sabine), Kast, K. (Karin), Varon-Mateeva, R. (Raymonda), Gehrig, P.A. (Paola A.), Bojesen, A. (Anders), Pedersen, I.S. (Inge Sokilde), Sunde, L. (Lone), Jensen, U.B., Thomassen, M. (Mads), Kruse, T.A. (Torben), Foretova, L. (Lenka), Peterlongo, P. (Paolo), Bernard, L. (Loris), Peissel, B. (Bernard), Scuvera, G. (Giulietta), Manoukian, S. (Siranoush), Radice, P. (Paolo), Ottini, L. (Laura), Montagna, M. (Marco), Agata, S. (Simona), Maugard, C., Simard, J. (Jacques), Soucy, P. (Penny), Berger, A. (Annemarie), Fink-Retter, A. (Anneliese), Singer, C.F. (Christian), Rappaport, C. (Christine), Geschwantler Kaulich, D. (Daphne), Tea, M.-K., Pfeiler, G. (Georg), John, E.M. (Esther), Miron, A. (Alexander), Neuhausen, S.L. (Susan), Terry, M.B. (Mary Beth), Chung, W.K. (Wendy K.), Daly, M.B. (Mary), Goldgar, D. (David), Janavicius, R. (Ramunas), Dorfling, C.M. (Cecilia), Rensburg, E.J. (Elizabeth) van, Fostira, F. (Florentia), Konstantopoulou, I. (I.), Garber, J., Godwin, A.K. (Andrew), Olah, E., Narod, S.A. (Steven A.), Rennert, G. (Gad), Paluch, S.S. (Shani), Laitman, Y. (Yael), Friedman, E. (Eitan), Liljegren, A. (Annelie), Rantala, J. (Johanna), Stenmark-Askmalm, M. (Marie), Loman, N. (Niklas), Imyanitov, E.N. (Evgeny), Hamann, U. (Ute), Spurdle, A.B. (Amanda), Healey, S. (Sue), Weitzel, J.N. (Jeffrey), Herzog, J. (Josef), Margileth, D. (David), Gorrini, C. (Chiara), Esteller, M. (Manel), Gómez, A. (Antonio), Sayols, S. (Sergi), Vidal, E. (Enrique), Heyn, H. (Holger), Stoppa-Lyonnet, D. (Dominique), Léone, M. (Mélanie), Barjhoux, L. (Laure), Fassy-Colcombet, M. (Marion), Pauw, A. (Antoine) de, Lasset, C. (Christine), Ferrer, S.F., Castera, L. (Laurent), Berthet, P. (Pascaline), Cornelis, F. (Franco̧is), Bignon, Y.-J. (Yves-Jean), Damiola, F. (Francesca), Mazoyer, S. (Sylvie), Sinilnikova, O. (Olga), Maxwell, C.A. (Christopher), Vijai, J. (Joseph), Robson, M. (Mark), Kauff, N. (Noah), Corines, M.J. (Marina J.), Villano, D. (Danylko), Cunningham, J.M. (Julie), Lee, A. (Adam), Lindor, N.M. (Noralane), Lázaro, C. (Conxi), Easton, D.F. (Douglas), Offit, K. (Kenneth), Chenevix-Trench, G. (Georgia), Couch, F.J. (Fergus), Antoniou, A.C. (Antonis C.), and Pujana, M.A. (Miguel)
- Abstract
While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood appro
- Published
- 2015
- Full Text
- View/download PDF
31. Assessing Associations between the AURKA-HMMR-TPX2-TUBG1 Functional Module and Breast Cancer Risk in BRCA1/2 Mutation Carriers
- Author
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Blanco, I, Kuchenbaecker, K, Cuadras, D, Wang, XS, Barrowdale, D, Garibay, GR, Librado, P, Sanchez-Gracia, A, Rozas, J, Bonifaci, N, McGuffog, L, Pankratz, VS, Islam, A, Mateo, F, Berenguer, A, Petit, A, Catala, I, Brunet, J, Feliubadalo, L, Tornero, E, Benitez, J, Osorio, A, Cajal, TRY, Nevanlinna, H, Aittomaki, K, Arun, BK, Toland, AE, Karlan, BY, Walsh, C, Lester, J, Greene, MH, Mai, PL, Nussbaum, RL, Andrulis, IL, Domchek, SM, Nathanson, KL, Rebbeck, TR, Barkardottir, RB, Jakubowska, A, Lubinski, J, Durda, K, Jaworska-Bieniek, K, Claes, K, Van Maerken, T, Diez, O, Hansen, TV, Jonson, L, Gerdes, AM, Ejlertsen, B, de la Hoya, M, Caldees, T, Dunning, AM, Oliver, C, Fineberg, E, Cook, M, Peock, S, McCann, E, Murray, A, Jacobs, C, Pichert, G, Lalloo, F, Chu, C, Dorkins, H, Paterson, J, Ong, KR, Teixeira, MR, Teixeira, Hogervorst, FBL, van der Hout, AH, Seynaeve, Caroline, van der Luijt, RB, Ligtenberg, MJL, Devilee, P, Wijnen, JT, Rookus, MA, Meijers-Heijboer, HEJ, Blok, MJ, van den Ouweland, Ans, Aalfs, CM, Rodriguez, GC, Phillips, KAA, Piedmonte, M, Nerenstone, SR, Bae-Jump, VL, O'Malley, DM, Ratner, ES, Schmutzler, RK, Wappenschmidt, B, Rhiem, K, Engel, C, Meindl, A, Ditsch, N, Arnold, N, Plendl, HJ, Niederacher, D, Sutter, C, Wang-Gohrke, S, Steinemann, D, Preisler-Adams, S, Kast, K, Varon-Mateeva, R, Gehrig, A, Bojesen, A, Pedersen, IS, Sunde, L, Jensen, UB, Thomassen, Marga, Kruse, TA, Foretova, L, Peterlongo, P, Bernard, L, Peissel, B, Scuvera, G, Manoukian, S, Radice, P, Ottini, L, Montagna, M, Agata, S, Maugard, C, Simard, J, Soucy, P, Berger, A, Fink-Retter, A, Singer, CF, Rappaport, C, Geschwantler-Kaulich, D, Tea, MK, Pfeiler, G, John, EM, Miron, A, Neuhausen, SL, Terry, MB, Chung, WK, Daly, MB, Goldgar, DE, Janavicius, R, Dorfling, CM, van Rensburg, EJ, Fostira, F, Konstantopoulou, I, Garber, J, Godwin, AK, Olah, E, Narod, SA, Rennert, G, Paluch, SS, Laitman, Y, Friedman, E, Liljegren, A, Rantala, J, Stenmark-Askmalm, M, Loman, N, Imyanitov, EN, Hamann, U, Spurdle, AB, Healey, S, Weitzel, JN, Herzog, J, Margileth, D, Gorrini, C, Esteller, M, Gomez, A, Sayols, S, Vidal, E, Heyn, H, Stoppa-Lyonnet, Leone, M, Barjhoux, L, Fassy-Colcombet, M, de Pauw, A, Lasset, C, Ferrer, SF, Castera, L, Berthet, P, Cornelis, F, Bignon, YJ, Damiola, F, Mazoyer, S, Sinilnikova, OM, Maxwell, CA, Vijai, J, Robson, M, Kauff, N, Corines, MJ, Villano, D, Cunningham, J, van der Lee, A, Lindor, N, Lazaro, C (Conxi), Easton, DF, Offit, K, Chenevix-Trench, G, Couch, FJ, Antoniou, AC, Pujana, MA, Blanco, I, Kuchenbaecker, K, Cuadras, D, Wang, XS, Barrowdale, D, Garibay, GR, Librado, P, Sanchez-Gracia, A, Rozas, J, Bonifaci, N, McGuffog, L, Pankratz, VS, Islam, A, Mateo, F, Berenguer, A, Petit, A, Catala, I, Brunet, J, Feliubadalo, L, Tornero, E, Benitez, J, Osorio, A, Cajal, TRY, Nevanlinna, H, Aittomaki, K, Arun, BK, Toland, AE, Karlan, BY, Walsh, C, Lester, J, Greene, MH, Mai, PL, Nussbaum, RL, Andrulis, IL, Domchek, SM, Nathanson, KL, Rebbeck, TR, Barkardottir, RB, Jakubowska, A, Lubinski, J, Durda, K, Jaworska-Bieniek, K, Claes, K, Van Maerken, T, Diez, O, Hansen, TV, Jonson, L, Gerdes, AM, Ejlertsen, B, de la Hoya, M, Caldees, T, Dunning, AM, Oliver, C, Fineberg, E, Cook, M, Peock, S, McCann, E, Murray, A, Jacobs, C, Pichert, G, Lalloo, F, Chu, C, Dorkins, H, Paterson, J, Ong, KR, Teixeira, MR, Teixeira, Hogervorst, FBL, van der Hout, AH, Seynaeve, Caroline, van der Luijt, RB, Ligtenberg, MJL, Devilee, P, Wijnen, JT, Rookus, MA, Meijers-Heijboer, HEJ, Blok, MJ, van den Ouweland, Ans, Aalfs, CM, Rodriguez, GC, Phillips, KAA, Piedmonte, M, Nerenstone, SR, Bae-Jump, VL, O'Malley, DM, Ratner, ES, Schmutzler, RK, Wappenschmidt, B, Rhiem, K, Engel, C, Meindl, A, Ditsch, N, Arnold, N, Plendl, HJ, Niederacher, D, Sutter, C, Wang-Gohrke, S, Steinemann, D, Preisler-Adams, S, Kast, K, Varon-Mateeva, R, Gehrig, A, Bojesen, A, Pedersen, IS, Sunde, L, Jensen, UB, Thomassen, Marga, Kruse, TA, Foretova, L, Peterlongo, P, Bernard, L, Peissel, B, Scuvera, G, Manoukian, S, Radice, P, Ottini, L, Montagna, M, Agata, S, Maugard, C, Simard, J, Soucy, P, Berger, A, Fink-Retter, A, Singer, CF, Rappaport, C, Geschwantler-Kaulich, D, Tea, MK, Pfeiler, G, John, EM, Miron, A, Neuhausen, SL, Terry, MB, Chung, WK, Daly, MB, Goldgar, DE, Janavicius, R, Dorfling, CM, van Rensburg, EJ, Fostira, F, Konstantopoulou, I, Garber, J, Godwin, AK, Olah, E, Narod, SA, Rennert, G, Paluch, SS, Laitman, Y, Friedman, E, Liljegren, A, Rantala, J, Stenmark-Askmalm, M, Loman, N, Imyanitov, EN, Hamann, U, Spurdle, AB, Healey, S, Weitzel, JN, Herzog, J, Margileth, D, Gorrini, C, Esteller, M, Gomez, A, Sayols, S, Vidal, E, Heyn, H, Stoppa-Lyonnet, Leone, M, Barjhoux, L, Fassy-Colcombet, M, de Pauw, A, Lasset, C, Ferrer, SF, Castera, L, Berthet, P, Cornelis, F, Bignon, YJ, Damiola, F, Mazoyer, S, Sinilnikova, OM, Maxwell, CA, Vijai, J, Robson, M, Kauff, N, Corines, MJ, Villano, D, Cunningham, J, van der Lee, A, Lindor, N, Lazaro, C (Conxi), Easton, DF, Offit, K, Chenevix-Trench, G, Couch, FJ, Antoniou, AC, and Pujana, MA
- Abstract
While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood approach. The association of HMMR rs299290 with breast cancer risk in BRCA1 mutation carriers was confirmed: per-allele hazard ratio (HR) = 1.10, 95% confidence interval (CI) 1.04 - 1.15, p = 1.9 x 10(-4) (false discovery rate (FDR)-adjusted p = 0.043). Variation in CSTF1, located next to AURKA, was also found to be associated with breast cancer risk in BRCA2 mutation carriers: rs2426618 per-allele HR = 1.10, 95% CI 1.03 - 1.16, p = 0.005 (FDR-adjusted p = 0.045). Assessment of pairwise interactions provided suggestions (FDR-adjusted p(interaction) values > 0.05) for deviations from the multiplicative model for rs299290 and CSTF1 rs6064391, and rs299290 and TUBG1 rs11649877 in both BRCA1 and BRCA2 mutation carriers. Following these suggestions, the expression of HMMR and AURKA or TUBG1 in sporadic breast tumors was found to potentially interact, influencing patients' survival. Together, the results of this study support the hypothesis of a causative link between altered function of AURKA-HMMR-TPX2-TUBG1 and breast carcinogenesis in BRCA1/2 mutation carriers.
- Published
- 2015
32. Computer aided cytometry in high grade malignant non-Hodgkin’s lymphomas and tonsils
- Author
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Bergmann, M., Heyn, H., Harms, H., and Müller-Hermelink, H. K.
- Published
- 1989
- Full Text
- View/download PDF
33. DNA methylation profiling in breast cancer discordant identical twins identifies DOK7 as novel epigenetic biomarker
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Heyn H, Carmona FJ, Gomez A, Ferreira HJ, Bell JT, Sayols S, Ward K, Stefansson OA, Moran S, Sandoval J, Eyfjord JE, Spector TD, and Esteller M
- Abstract
Using whole blood from 15 twin pairs discordant for breast cancer and high-resolution (450K) DNA methylation analysis, we identified 403 differentially methylated CpG sites including known and novel potential breast cancer genes. Confirming the results in an independent validation cohort of 21 twin pairs determined the docking protein DOK7 as a candidate for blood-based cancer diagnosis. DNA hypermethylation of the promoter region was also seen in primary breast cancer tissues and cancer cell lines. Hypermethylation of DOK7 occurs years before tumor diagnosis, suggesting a role as a powerful epigenetic blood-based biomarker as well as providing insights into breast cancer pathogenesis.
- Published
- 2013
34. Validation of a DNA methylation microarray for 450,000 CpG sites in the human genome
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Sandoval J, Heyn H, Moran S, Serra-Musach J, Pujana MA, Bibikova M, and Esteller M
- Abstract
DNA methylation is the most studied epigenetic mark and CpG methylation is central to many biological processes and human diseases. Since cancer has highlighted the contribution to disease of aberrant DNA methylation patterns, such as the presence of promoter CpG island hypermethylation-associated silencing of tumor suppressor genes and global DNA hypomethylation defects, their importance will surely become apparent in other pathologies. However, advances in obtaining comprehensive DNA methylomes are hampered by the high cost and time-consuming aspects of the single nucleotide methods currently available for whole genome DNA methylation analyses. Following the success of the standard CpG methylation microarrays for 1,505 CpG sites and 27,000 CpG sites, we have validated in vivo the newly developed 450,000 (450K) cytosine microarray (Illumina). The 450K microarray includes CpG and CNG sites, CpG islands/shores/shelves/open sea, non-coding RNA (microRNAs and long non-coding RNAs) and sites surrounding the transcription start sites (-200 bp to -1,500 bp, 5'-UTRs and exons 1) for coding genes, but also for the corresponding gene bodies and 3'-UTRs, in addition to intergenic regions derived from GWAS studies. Herein, we demonstrate that the 450K DNA methylation array can consistently and significantly detect CpG methylation changes in the HCT-116 colorectal cancer cell line in comparison with normal colon mucosa or HCT-116 cells with defective DNA methyltransferases (DKO). The provided validation highlights the potential use of the 450K DNA methylation microarray as a useful tool for ongoing and newly designed epigenome projects.
- Published
- 2011
35. DNMT3A mutations mediate the epigenetic reactivation of the leukemogenic factor MEIS1 in acute myeloid leukemia
- Author
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Ferreira, H J, primary, Heyn, H, additional, Vizoso, M, additional, Moutinho, C, additional, Vidal, E, additional, Gomez, A, additional, Martínez-Cardús, A, additional, Simó-Riudalbas, L, additional, Moran, S, additional, Jost, E, additional, and Esteller, M, additional
- Published
- 2015
- Full Text
- View/download PDF
36. Impaired DICER1 function promotes stemness and metastasis in colon cancer
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Iliou, M S, primary, da Silva-Diz, V, additional, Carmona, F J, additional, Ramalho-Carvalho, J, additional, Heyn, H, additional, Villanueva, A, additional, Muñoz, P, additional, and Esteller, M, additional
- Published
- 2013
- Full Text
- View/download PDF
37. DNA methylation profiling in breast cancer discordant identical twins identifies DOK7 as novel epigenetic biomarker
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Heyn, H., primary, Carmona, F. J., additional, Gomez, A., additional, Ferreira, H. J., additional, Bell, J. T., additional, Sayols, S., additional, Ward, K., additional, Stefansson, O. A., additional, Moran, S., additional, Sandoval, J., additional, Eyfjord, J. E., additional, Spector, T. D., additional, and Esteller, M., additional
- Published
- 2012
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- View/download PDF
38. Influence of inflammatory mechanisms on the redox balance in interstitial lung diseases
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Lenz, A.-G, primary, Hinze-Heyn, H, additional, Schneider, A, additional, Behr, J, additional, Häußinger, K, additional, Heindl, S, additional, Stanzel, F, additional, and Maier, K.L, additional
- Published
- 2004
- Full Text
- View/download PDF
39. The Expression of Human Relaxin in Yeast
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Yang, S., primary, Heyn, H., additional, Zhang, Y.Z., additional, Bullesbach, E.E., additional, and Schwabe, C., additional
- Published
- 1993
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- View/download PDF
40. Cetacean Relaxin
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Schwabe, C, Böllesbach, E E, Heyn, H, and Yoshioka, M
- Abstract
The tendency toward extremely high variability among relaxing derived from purportedly closely related species has come to an abrupt end with the discovery of quasi-porcine relaxin in the minke whale (Balaenoptera acutorostrata) and the Bryde's whale (Balaenoptera edeni). An aqueous abstract of the corpora lutea of the two baleen whales contained significant amounts of relaxin-like activity as determined by a mouse bioassay and by cross-reactivity with anti-pig relaxin antibodies. The activity could be isolated and purified to homogeneity. Sequence analysis revealed that both whale relaxins differed from each other by about 3 residues, whereas the relaxin of B. edenidiffered at only one position from that of pig relaxin. The similarity appears to include even the chain length heterogeneity observed at the C-terminal end of the B chain in porcine relaxin which is produced by a peculiar mode of connecting peptide removal from the prohormone. This finding may well represent one of the better documented challenges to the current paradigm of molecular evolution.
- Published
- 1989
- Full Text
- View/download PDF
41. Computer aided cytometry in high grade malignant non-Hodgkin's lymphomas and tonsils
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Hans Konrad Müller-Hermelink, Heyn H, Harms H, and Bergmann M
- Subjects
Pathology ,medicine.medical_specialty ,Hodgkin s ,Cell type ,Multivariate analysis ,business.industry ,Chronic tonsillitis ,Lymphoma, Non-Hodgkin ,Palatine Tonsil ,High resolution ,Color ,Lymphatic tissues ,Feature (computer vision) ,hemic and lymphatic diseases ,Multivariate Analysis ,medicine ,Image Processing, Computer-Assisted ,Humans ,Lymphocytes ,business ,Cytometry - Abstract
The aim of the study is to establish quantitative cytological criteria for reliable diagnoses in high grade malignant non-Hodgkin's lymphomas (NHL). For this purpose Pappenheim-stained cytologic imprints from 15 cases of high grade malignant NHL and ten cases of chronic tonsillitis have been analysed using a TV-microscope system, high resolution color scanning (13.3 pixel/microns), and image processing on a computer. The highly reliable computer-extracted cell features can be used to discriminate the different cell types of malignant NHL. Because of a considerable overlap, no feature on its own is sufficient to discriminate all the different cells. Only multivariate analysis of a suitable combination of features allows reliable discrimination. The results show that the different cells defined by subjective morphological criteria in the Kiel-classification of malignant NHL also form distinctive subpopulations with regard to their objective mathematical cell features and show distinctive differences when compared with their benign counterparts derived from reactive lymphatic tissue.
- Published
- 1989
42. DNMT3A mutations mediate the epigenetic reactivation of the leukemogenic factor MEIS1 in acute myeloid leukemia
- Author
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Ferreira, H. J., Heyn, H., Vizoso, M., Moutinho, C., Vidal, E., Gomez, A., Martínez-Cardús, A., Simó-Riudalbas, L., Moran, S., Jost, Edgar, and Esteller, M.
- Subjects
3. Good health - Abstract
Oncogene : including Oncogene reviews 35(23), 3079-3082 (2016). doi:10.1038/onc.2015.359, Published by Nature Publ. Group, Basingstoke
43. A Landscape of Pharmacogenomic Interactions in Cancer
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Francesco Iorio, Ta, Knijnenburg, Dj, Vis, Gr, Bignell, Mp, Menden, Schubert M, Aben N, Gonçalves E, Barthorpe S, Lightfoot H, Cokelaer T, Greninger P, van Dyk E, Chang H, de Silva H, Heyn H, Deng X, Rk, Egan, Liu Q, and Mironenko T
44. Bromination of 2-pyrazolines and 3,4,5-trimethylpyrazole
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Closs, G.L., primary and Heyn, H., additional
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- 1966
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- View/download PDF
45. 268P Impact of B cell and plasma cell infiltration on survival in early-stage breast cancer (BC) without recurrence.
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Angelats, L., Brunet, L. Pare, Rubio-Perez, C., Torres, E. Sanfeliu, Solis, E. Segui, Villacampa, G., Marin, M., Conte, B., Saez, O. Martinez, Fernandez-Martinez, A., Buckingham, W., Guedan, S., Heyn, H., Vivancos, A., Parker, J., Gonzalez, P. Villagrasa, Perou, C.M., Prat, A., and Maristany, F. Braso
- Subjects
- *
PLASMA cells , *B cells , *CELL survival , *BREAST cancer - Published
- 2024
- Full Text
- View/download PDF
46. Machine Learning Identifies Stemness Features Associated with Oncogenic Dedifferentiation
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Tathiane M. Malta, Artem Sokolov, Andrew J. Gentles, Tomasz Burzykowski, Laila Poisson, John N. Weinstein, Bożena Kamińska, Joerg Huelsken, Larsson Omberg, Olivier Gevaert, Antonio Colaprico, Patrycja Czerwińska, Sylwia Mazurek, Lopa Mishra, Holger Heyn, Alex Krasnitz, Andrew K. Godwin, Alexander J. Lazar, Joshua M. Stuart, Katherine A. Hoadley, Peter W. Laird, Houtan Noushmehr, Maciej Wiznerowicz, Samantha J. Caesar-Johnson, John A. Demchok, Ina Felau, Melpomeni Kasapi, Martin L. Ferguson, Carolyn M. Hutter, Heidi J. Sofia, Roy Tarnuzzer, Zhining Wang, Liming Yang, Jean C. Zenklusen, Jiashan (Julia) Zhang, Sudha Chudamani, Jia Liu, Laxmi Lolla, Rashi Naresh, Todd Pihl, Qiang Sun, Yunhu Wan, Ye Wu, Juok Cho, Timothy DeFreitas, Scott Frazer, Nils Gehlenborg, Gad Getz, David I. Heiman, Jaegil Kim, Michael S. Lawrence, Pei Lin, Sam Meier, Michael S. Noble, Gordon Saksena, Doug Voet, Hailei Zhang, Brady Bernard, Nyasha Chambwe, Varsha Dhankani, Theo Knijnenburg, Roger Kramer, Kalle Leinonen, Yuexin Liu, Michael Miller, Sheila Reynolds, Ilya Shmulevich, Vesteinn Thorsson, Wei Zhang, Rehan Akbani, Bradley M. Broom, Apurva M. Hegde, Zhenlin Ju, Rupa S. Kanchi, Anil Korkut, Jun Li, Han Liang, Shiyun Ling, Wenbin Liu, Yiling Lu, Gordon B. Mills, Kwok-Shing Ng, Arvind Rao, Michael Ryan, Jing Wang, Jiexin Zhang, Adam Abeshouse, Joshua Armenia, Debyani Chakravarty, Walid K. Chatila, Ino de Bruijn, Jianjiong Gao, Benjamin E. Gross, Zachary J. Heins, Ritika Kundra, Konnor La, Marc Ladanyi, Augustin Luna, Moriah G. Nissan, Angelica Ochoa, Sarah M. Phillips, Ed Reznik, Francisco Sanchez-Vega, Chris Sander, Nikolaus Schultz, Robert Sheridan, S. Onur Sumer, Yichao Sun, Barry S. Taylor, Jioajiao Wang, Hongxin Zhang, Pavana Anur, Myron Peto, Paul Spellman, Christopher Benz, Christopher K. Wong, Christina Yau, D. Neil Hayes, Joel S. Parker, Matthew D. Wilkerson, Adrian Ally, Miruna Balasundaram, Reanne Bowlby, Denise Brooks, Rebecca Carlsen, Eric Chuah, Noreen Dhalla, Robert Holt, Steven J.M. Jones, Katayoon Kasaian, Darlene Lee, Yussanne Ma, Marco A. Marra, Michael Mayo, Richard A. Moore, Andrew J. Mungall, Karen Mungall, A. Gordon Robertson, Sara Sadeghi, Jacqueline E. Schein, Payal Sipahimalani, Angela Tam, Nina Thiessen, Kane Tse, Tina Wong, Ashton C. Berger, Rameen Beroukhim, Andrew D. Cherniack, Carrie Cibulskis, Stacey B. Gabriel, Galen F. Gao, Gavin Ha, Matthew Meyerson, Steven E. Schumacher, Juliann Shih, Melanie H. Kucherlapati, Raju S. Kucherlapati, Stephen Baylin, Leslie Cope, Ludmila Danilova, Moiz S. Bootwalla, Phillip H. Lai, Dennis T. Maglinte, David J. Van Den Berg, Daniel J. Weisenberger, J. Todd Auman, Saianand Balu, Tom Bodenheimer, Cheng Fan, Alan P. Hoyle, Stuart R. Jefferys, Corbin D. Jones, Shaowu Meng, Piotr A. Mieczkowski, Lisle E. Mose, Amy H. Perou, Charles M. Perou, Jeffrey Roach, Yan Shi, Janae V. Simons, Tara Skelly, Matthew G. Soloway, Donghui Tan, Umadevi Veluvolu, Huihui Fan, Toshinori Hinoue, Hui Shen, Wanding Zhou, Michelle Bellair, Kyle Chang, Kyle Covington, Chad J. Creighton, Huyen Dinh, HarshaVardhan Doddapaneni, Lawrence A. Donehower, Jennifer Drummond, Richard A. Gibbs, Robert Glenn, Walker Hale, Yi Han, Jianhong Hu, Viktoriya Korchina, Sandra Lee, Lora Lewis, Wei Li, Xiuping Liu, Margaret Morgan, Donna Morton, Donna Muzny, Jireh Santibanez, Margi Sheth, Eve Shinbrot, Linghua Wang, Min Wang, David A. Wheeler, Liu Xi, Fengmei Zhao, Julian Hess, Elizabeth L. Appelbaum, Matthew Bailey, Matthew G. Cordes, Li Ding, Catrina C. Fronick, Lucinda A. Fulton, Robert S. Fulton, Cyriac Kandoth, Elaine R. Mardis, Michael D. McLellan, Christopher A. Miller, Heather K. Schmidt, Richard K. Wilson, Daniel Crain, Erin Curley, Johanna Gardner, Kevin Lau, David Mallery, Scott Morris, Joseph Paulauskis, Robert Penny, Candace Shelton, Troy Shelton, Mark Sherman, Eric Thompson, Peggy Yena, Jay Bowen, Julie M. Gastier-Foster, Mark Gerken, Kristen M. Leraas, Tara M. Lichtenberg, Nilsa C. Ramirez, Lisa Wise, Erik Zmuda, Niall Corcoran, Tony Costello, Christopher Hovens, Andre L. Carvalho, Ana C. de Carvalho, José H. Fregnani, Adhemar Longatto-Filho, Rui M. Reis, Cristovam Scapulatempo-Neto, Henrique C.S. Silveira, Daniel O. Vidal, Andrew Burnette, Jennifer Eschbacher, Beth Hermes, Ardene Noss, Rosy Singh, Matthew L. Anderson, Patricia D. Castro, Michael Ittmann, David Huntsman, Bernard Kohl, Xuan Le, Richard Thorp, Chris Andry, Elizabeth R. Duffy, Vladimir Lyadov, Oxana Paklina, Galiya Setdikova, Alexey Shabunin, Mikhail Tavobilov, Christopher McPherson, Ronald Warnick, Ross Berkowitz, Daniel Cramer, Colleen Feltmate, Neil Horowitz, Adam Kibel, Michael Muto, Chandrajit P. Raut, Andrei Malykh, Jill S. Barnholtz-Sloan, Wendi Barrett, Karen Devine, Jordonna Fulop, Quinn T. Ostrom, Kristen Shimmel, Yingli Wolinsky, Andrew E. Sloan, Agostino De Rose, Felice Giuliante, Marc Goodman, Beth Y. Karlan, Curt H. Hagedorn, John Eckman, Jodi Harr, Jerome Myers, Kelinda Tucker, Leigh Anne Zach, Brenda Deyarmin, Hai Hu, Leonid Kvecher, Caroline Larson, Richard J. Mural, Stella Somiari, Ales Vicha, Tomas Zelinka, Joseph Bennett, Mary Iacocca, Brenda Rabeno, Patricia Swanson, Mathieu Latour, Louis Lacombe, Bernard Têtu, Alain Bergeron, Mary McGraw, Susan M. Staugaitis, John Chabot, Hanina Hibshoosh, Antonia Sepulveda, Tao Su, Timothy Wang, Olga Potapova, Olga Voronina, Laurence Desjardins, Odette Mariani, Sergio Roman-Roman, Xavier Sastre, Marc-Henri Stern, Feixiong Cheng, Sabina Signoretti, Andrew Berchuck, Darell Bigner, Eric Lipp, Jeffrey Marks, Shannon McCall, Roger McLendon, Angeles Secord, Alexis Sharp, Madhusmita Behera, Daniel J. Brat, Amy Chen, Keith Delman, Seth Force, Fadlo Khuri, Kelly Magliocca, Shishir Maithel, Jeffrey J. Olson, Taofeek Owonikoko, Alan Pickens, Suresh Ramalingam, Dong M. Shin, Gabriel Sica, Erwin G. Van Meir, Hongzheng Zhang, Wil Eijckenboom, Ad Gillis, Esther Korpershoek, Leendert Looijenga, Wolter Oosterhuis, Hans Stoop, Kim E. van Kessel, Ellen C. Zwarthoff, Chiara Calatozzolo, Lucia Cuppini, Stefania Cuzzubbo, Francesco DiMeco, Gaetano Finocchiaro, Luca Mattei, Alessandro Perin, Bianca Pollo, Chu Chen, John Houck, Pawadee Lohavanichbutr, Arndt Hartmann, Christine Stoehr, Robert Stoehr, Helge Taubert, Sven Wach, Bernd Wullich, Witold Kycler, Dawid Murawa, Ki Chung, W. Jeffrey Edenfield, Julie Martin, Eric Baudin, Glenn Bubley, Raphael Bueno, Assunta De Rienzo, William G. Richards, Steven Kalkanis, Tom Mikkelsen, Lisa Scarpace, Nicolas Girard, Marta Aymerich, Elias Campo, Eva Giné, Armando López Guillermo, Nguyen Van Bang, Phan Thi Hanh, Bui Duc Phu, Yufang Tang, Howard Colman, Kimberley Evason, Peter R. Dottino, John A. Martignetti, Hani Gabra, Hartmut Juhl, Teniola Akeredolu, Serghei Stepa, Dave Hoon, Keunsoo Ahn, Koo Jeong Kang, Felix Beuschlein, Anne Breggia, Michael Birrer, Debra Bell, Mitesh Borad, Alan H. Bryce, Erik Castle, Vishal Chandan, John Cheville, John A. Copland, Michael Farnell, Thomas Flotte, Nasra Giama, Thai Ho, Michael Kendrick, Jean-Pierre Kocher, Karla Kopp, Catherine Moser, David Nagorney, Daniel O’Brien, Brian Patrick O’Neill, Tushar Patel, Gloria Petersen, Florencia Que, Michael Rivera, Lewis Roberts, Robert Smallridge, Thomas Smyrk, Melissa Stanton, R. Houston Thompson, Michael Torbenson, Ju Dong Yang, Lizhi Zhang, Fadi Brimo, Jaffer A. Ajani, Ana Maria Angulo Gonzalez, Carmen Behrens, Jolanta Bondaruk, Russell Broaddus, Bogdan Czerniak, Bita Esmaeli, Junya Fujimoto, Jeffrey Gershenwald, Charles Guo, Christopher Logothetis, Funda Meric-Bernstam, Cesar Moran, Lois Ramondetta, David Rice, Anil Sood, Pheroze Tamboli, Timothy Thompson, Patricia Troncoso, Anne Tsao, Ignacio Wistuba, Candace Carter, Lauren Haydu, Peter Hersey, Valerie Jakrot, Hojabr Kakavand, Richard Kefford, Kenneth Lee, Georgina Long, Graham Mann, Michael Quinn, Robyn Saw, Richard Scolyer, Kerwin Shannon, Andrew Spillane, Jonathan Stretch, Maria Synott, John Thompson, James Wilmott, Hikmat Al-Ahmadie, Timothy A. Chan, Ronald Ghossein, Anuradha Gopalan, Douglas A. Levine, Victor Reuter, Samuel Singer, Bhuvanesh Singh, Nguyen Viet Tien, Thomas Broudy, Cyrus Mirsaidi, Praveen Nair, Paul Drwiega, Judy Miller, Jennifer Smith, Howard Zaren, Joong-Won Park, Nguyen Phi Hung, Electron Kebebew, W. Marston Linehan, Adam R. Metwalli, Karel Pacak, Peter A. Pinto, Mark Schiffman, Laura S. Schmidt, Cathy D. Vocke, Nicolas Wentzensen, Robert Worrell, Hannah Yang, Marc Moncrieff, Chandra Goparaju, Jonathan Melamed, Harvey Pass, Natalia Botnariuc, Irina Caraman, Mircea Cernat, Inga Chemencedji, Adrian Clipca, Serghei Doruc, Ghenadie Gorincioi, Sergiu Mura, Maria Pirtac, Irina Stancul, Diana Tcaciuc, Monique Albert, Iakovina Alexopoulou, Angel Arnaout, John Bartlett, Jay Engel, Sebastien Gilbert, Jeremy Parfitt, Harman Sekhon, George Thomas, Doris M. Rassl, Robert C. Rintoul, Carlo Bifulco, Raina Tamakawa, Walter Urba, Nicholas Hayward, Henri Timmers, Anna Antenucci, Francesco Facciolo, Gianluca Grazi, Mirella Marino, Roberta Merola, Ronald de Krijger, Anne-Paule Gimenez-Roqueplo, Alain Piché, Simone Chevalier, Ginette McKercher, Kivanc Birsoy, Gene Barnett, Cathy Brewer, Carol Farver, Theresa Naska, Nathan A. Pennell, Daniel Raymond, Cathy Schilero, Kathy Smolenski, Felicia Williams, Carl Morrison, Jeffrey A. Borgia, Michael J. Liptay, Mark Pool, Christopher W. Seder, Kerstin Junker, Mikhail Dinkin, George Manikhas, Domenico Alvaro, Maria Consiglia Bragazzi, Vincenzo Cardinale, Guido Carpino, Eugenio Gaudio, David Chesla, Sandra Cottingham, Michael Dubina, Fedor Moiseenko, Renumathy Dhanasekaran, Karl-Friedrich Becker, Klaus-Peter Janssen, Julia Slotta-Huspenina, Mohamed H. Abdel-Rahman, Dina Aziz, Sue Bell, Colleen M. Cebulla, Amy Davis, Rebecca Duell, J. Bradley Elder, Joe Hilty, Bahavna Kumar, James Lang, Norman L. Lehman, Randy Mandt, Phuong Nguyen, Robert Pilarski, Karan Rai, Lynn Schoenfield, Kelly Senecal, Paul Wakely, Paul Hansen, Ronald Lechan, James Powers, Arthur Tischler, William E. Grizzle, Katherine C. Sexton, Alison Kastl, Joel Henderson, Sima Porten, Jens Waldmann, Martin Fassnacht, Sylvia L. Asa, Dirk Schadendorf, Marta Couce, Markus Graefen, Hartwig Huland, Guido Sauter, Thorsten Schlomm, Ronald Simon, Pierre Tennstedt, Oluwole Olabode, Mark Nelson, Oliver Bathe, Peter R. Carroll, June M. Chan, Philip Disaia, Pat Glenn, Robin K. Kelley, Charles N. Landen, Joanna Phillips, Michael Prados, Jeffry Simko, Karen Smith-McCune, Scott VandenBerg, Kevin Roggin, Ashley Fehrenbach, Ady Kendler, Suzanne Sifri, Ruth Steele, Antonio Jimeno, Francis Carey, Ian Forgie, Massimo Mannelli, Michael Carney, Brenda Hernandez, Benito Campos, Christel Herold-Mende, Christin Jungk, Andreas Unterberg, Andreas von Deimling, Aaron Bossler, Joseph Galbraith, Laura Jacobus, Michael Knudson, Tina Knutson, Deqin Ma, Mohammed Milhem, Rita Sigmund, Rashna Madan, Howard G. Rosenthal, Clement Adebamowo, Sally N. Adebamowo, Alex Boussioutas, David Beer, Thomas Giordano, Anne-Marie Mes-Masson, Fred Saad, Therese Bocklage, Lisa Landrum, Robert Mannel, Kathleen Moore, Katherine Moxley, Russel Postier, Joan Walker, Rosemary Zuna, Michael Feldman, Federico Valdivieso, Rajiv Dhir, James Luketich, Edna M. 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Aredes, Armaz Mariamidze, Malta T.M., Sokolov A., Gentles A.J., Burzykowski T., Poisson L., Weinstein J.N., Kaminska B., Huelsken J., Omberg L., Gevaert O., Colaprico A., Czerwinska P., Mazurek S., Mishra L., Heyn H., Krasnitz A., Godwin A.K., Lazar A.J., Caesar-Johnson S.J., Demchok J.A., Felau I., Kasapi M., Ferguson M.L., Hutter C.M., Sofia H.J., Tarnuzzer R., Wang Z., Yang L., Zenklusen J.C., Zhang J.J., Chudamani S., Liu J., Lolla L., Naresh R., Pihl T., Sun Q., Wan Y., Wu Y., Cho J., DeFreitas T., Frazer S., Gehlenborg N., Getz G., Heiman D.I., Kim J., Lawrence M.S., Lin P., Meier S., Noble M.S., Saksena G., Voet D., Zhang H., Bernard B., Chambwe N., Dhankani V., Knijnenburg T., Kramer R., Leinonen K., Liu Y., Miller M., Reynolds S., Shmulevich I., Thorsson V., Zhang W., Akbani R., Broom B.M., Hegde A.M., Ju Z., Kanchi R.S., Korkut A., Li J., Liang H., Ling S., Liu W., Lu Y., Mills G.B., Ng K.-S., Rao A., Ryan M., Wang J., Zhang J., Abeshouse A., Armenia J., Chakravarty D., 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Jones C.D., Meng S., Mieczkowski P.A., Mose L.E., Perou A.H., Perou C.M., Roach J., Shi Y., Simons J.V., Skelly T., Soloway M.G., Tan D., Veluvolu U., Fan H., Hinoue T., Laird P.W., Shen H., Zhou W., Bellair M., Chang K., Covington K., Creighton C.J., Dinh H., Doddapaneni H., Donehower L.A., Drummond J., Gibbs R.A., Glenn R., Hale W., Han Y., Hu J., Korchina V., Lee S., Lewis L., Li W., Liu X., Morgan M., Morton D., Muzny D., Santibanez J., Sheth M., Shinbrot E., Wang L., Wang M., Wheeler D.A., Xi L., Zhao F., Hess J., Appelbaum E.L., Bailey M., Cordes M.G., Ding L., Fronick C.C., Fulton L.A., Fulton R.S., Kandoth C., Mardis E.R., McLellan M.D., Miller C.A., Schmidt H.K., Wilson R.K., Crain D., Curley E., Gardner J., Lau K., Mallery D., Morris S., Paulauskis J., Penny R., Shelton C., Shelton T., Sherman M., Thompson E., Yena P., Bowen J., Gastier-Foster J.M., Gerken M., Leraas K.M., Lichtenberg T.M., Ramirez N.C., Wise L., Zmuda E., Corcoran N., Costello T., Hovens C., Carvalho A.L., de Carvalho A.C., Fregnani J.H., Longatto-Filho A., Reis R.M., Scapulatempo-Neto C., Silveira H.C.S., Vidal D.O., Burnette A., Eschbacher J., Hermes B., Noss A., Singh R., Anderson M.L., Castro P.D., Ittmann M., Huntsman D., Kohl B., Le X., Thorp R., Andry C., Duffy E.R., Lyadov V., Paklina O., Setdikova G., Shabunin A., Tavobilov M., McPherson C., Warnick R., Berkowitz R., Cramer D., Feltmate C., Horowitz N., Kibel A., Muto M., Raut C.P., Malykh A., Barnholtz-Sloan J.S., Barrett W., Devine K., Fulop J., Ostrom Q.T., Shimmel K., Wolinsky Y., Sloan A.E., De Rose A., Giuliante F., Goodman M., Karlan B.Y., Hagedorn C.H., Eckman J., Harr J., Myers J., Tucker K., Zach L.A., Deyarmin B., Hu H., Kvecher L., Larson C., Mural R.J., Somiari S., Vicha A., Zelinka T., Bennett J., Iacocca M., Rabeno B., Swanson P., Latour M., Lacombe L., Tetu B., Bergeron A., McGraw M., Staugaitis S.M., Chabot J., Hibshoosh H., Sepulveda A., Su T., Wang T., Potapova O., Voronina O., Desjardins L., Mariani O., 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0301 basic medicine ,Carcinogenesis ,pan-cancer ,Cancer Genome Atlas Research Network ,medicine.disease_cause ,Biochemistry ,epigenomic ,Epigenesis, Genetic ,genomic ,Machine Learning ,GENE-EXPRESSION SIGNATURE ,TUMOR ,Neoplasms ,Databases, Genetic ,Tumor Microenvironment ,LS4_6 ,Stemness ,Neoplasm Metastasis ,610 Medicine & health ,Induced pluripotent stem cell ,11 Medical and Health Sciences ,Carcinogenesi ,Epigenomics ,Cancer stem cells ,Stem Cells ,PROLIFERATION ,MicroRNA ,Sciences bio-médicales et agricoles ,CANCER ,stemne ,Neoplasm Metastasi ,CONNECTIVITY MAP ,ALGORITMOS ,Stem cell ,Life Sciences & Biomedicine ,Human ,Biochemistry & Molecular Biology ,cancer stem cell ,The Cancer Genome Atlas ,Biology ,Article ,General Biochemistry, Genetics and Molecular Biology ,NO ,ANNEXIN 1 ,03 medical and health sciences ,Stem Cell ,Cancer stem cell ,medicine ,Humans ,Epigenetics ,EMBRYONIC STEM ,Tumor microenvironment ,Science & Technology ,Biochemistry, Genetics and Molecular Biology(all) ,dedifferentiation ,Cell Biology ,06 Biological Sciences ,Cell Dedifferentiation ,DNA Methylation ,Immune checkpoint ,SELF-RENEWAL ,MicroRNAs ,030104 developmental biology ,CELLS ,Cancer research ,Neoplasm ,OVEREXPRESSION ,The Cancer Genome Atla ,Transcriptome ,cancer stem cells ,machine learning ,stemness ,Genetics and Molecular Biology(all) ,Developmental Biology - Abstract
Cancer progression involves the gradual loss of a differentiated phenotype and acquisition of progenitor and stem-cell-like features. Here, we provide novel stemness indices for assessing the degree of oncogenic dedifferentiation. We used an innovative one-class logistic regression (OCLR) machine-learning algorithm to extract transcriptomic and epigenetic feature sets derived from non-transformed pluripotent stem cells and their differentiated progeny. Using OCLR, we were able to identify previously undiscovered biological mechanisms associated with the dedifferentiated oncogenic state. Analyses of the tumor microenvironment revealed unanticipated correlation of cancer stemness with immune checkpoint expression and infiltrating immune cells. We found that the dedifferentiated oncogenic phenotype was generally most prominent in metastatic tumors. Application of our stemness indices to single-cell data revealed patterns of intra-tumor molecular heterogeneity. Finally, the indices allowed for the identification of novel targets and possible targeted therapies aimed at tumor differentiation. Stemness features extracted from transcriptomic and epigenetic data from TCGA tumors reveal novel biological and clinical insight, as well as potential drug targets for anti-cancer therapies., 0, info:eu-repo/semantics/published
- Published
- 2018
47. RELIABILITY INVESTIGATIONS ON TWO SHUTDOWN SYSTEMS FOR A HELIUM-COOLED HTR.
- Author
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Schulz-Heyn, H
- Published
- 1971
48. FixNCut: A Practical Guide to Sample Preservation by Reversible Fixation for Single Cell Assays.
- Author
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Wang S, Jiménez-Gracia L, De Amaral AA, Vlachos IS, Plummer J, Heyn H, and Martelotto LG
- Abstract
The quality of standard single-cell experiments often depends on the immediate processing of cells or tissues post-harvest to preserve fragile and vulnerable cell populations, unless the samples are adequately fixed and stored. Despite the recent rise in popularity of probe-based and aldehyde-fixed RNA assays, these methods face limitations in species and target availability and are not suitable for immunoprofiling or assessing chromatin accessibility. Recently, a reversible fixation strategy known as FixNCut has been successfully deployed to separate sampling from downstream applications in a reproducible and robust manner, avoiding stress or necrosis-related artifacts. In this article, we present an optimized and robust practical guide to the FixNCut protocol to aid the end-to-end adaptation of this versatile method. This protocol not only decouples tissue or cell harvesting from single-cell assays but also enables a flexible and decentralized workflow that unlocks the potential for single-cell analysis as well as unconventional study designs that were previously considered unfeasible. Key features • Reversible fixation: Preserves cellular and molecular structures with the option to later reverse the fixation for downstream applications, maintaining cell integrity • Compatibility with single-cell assays: Supports single-cell genomic assays such as scRNA-seq and ATAC-seq, essential for high-resolution analysis of cell function and gene expression • Flexibility in sample handling: Allows immediate fixation post-collection, decoupling sample processing from analysis, beneficial in settings where immediate processing is impractical • Preservation of RNA and DNA integrity: Effectively preserves RNA and DNA, reducing degradation to ensure accurate transcriptomic and genomic profiling • Suitability for various biological samples: Applicable to a wide range of biological samples, including tissues and cell suspensions, whether freshly isolated or post-dissociated • Enables multi-center studies: Facilitates collaborative research across multiple centers by allowing sample fixation at the point of collection, enhancing research scale and diversity • Avoidance of artifacts: Minimizes stress or necrosis-related artifacts, preserving the natural cellular physiology for accurate genomic and transcriptomic analysis., Competing Interests: Competing interestsH.H. is a co-founder and shareholder of Omniscope, a scientific advisory board member of MiRXES and Nanostring, and a consultant to Moderna and Singularity. L.G.M is an advisor and shareholder of Omniscope, and advisor for ArgenTAG and BioScryb. Omniscope has filed a patent related to the application of the FixNCut protocol. All other authors declare no competing interests., (©Copyright : © 2024 The Authors; This is an open access article under the CC BY-NC license.)
- Published
- 2024
- Full Text
- View/download PDF
49. Spatiotemporal omics for biology and medicine.
- Author
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Liu L, Chen A, Li Y, Mulder J, Heyn H, and Xu X
- Subjects
- Humans, Animals, Proteomics, Genomics
- Abstract
The completion of the Human Genome Project has provided a foundational blueprint for understanding human life. Nonetheless, understanding the intricate mechanisms through which our genetic blueprint is involved in disease or orchestrates development across temporal and spatial dimensions remains a profound scientific challenge. Recent breakthroughs in cellular omics technologies have paved new pathways for understanding the regulation of genomic elements and the relationship between gene expression, cellular functions, and cell fate determination. The advent of spatial omics technologies, encompassing both imaging and sequencing-based methodologies, has enabled a comprehensive understanding of biological processes from a cellular ecosystem perspective. This review offers an updated overview of how spatial omics has advanced our understanding of the translation of genetic information into cellular heterogeneity and tissue structural organization and their dynamic changes over time. It emphasizes the discovery of various biological phenomena, related to organ functionality, embryogenesis, species evolution, and the pathogenesis of diseases., Competing Interests: Declaration of interests X.X., L.L., A.C., and Y.L. are the co-inventors of Stereo-seq technology. The chip, procedure, and applications of Stereo-seq are covered in pending patents., (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
50. Systematic mapping of organism-scale gene-regulatory networks in aging using population asynchrony.
- Author
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Eder M, Martin OMF, Oswal N, Sedlackova L, Moutinho C, Del Carmen-Fabregat A, Menendez Bravo S, Sebé-Pedrós A, Heyn H, and Stroustrup N
- Subjects
- Animals, Caenorhabditis elegans Proteins metabolism, Caenorhabditis elegans Proteins genetics, RNA, Messenger metabolism, RNA, Messenger genetics, Caenorhabditis elegans genetics, Caenorhabditis elegans physiology, Aging genetics, Gene Regulatory Networks, Transcriptome genetics, Longevity genetics
- Abstract
In aging, physiologic networks decline in function at rates that differ between individuals, producing a wide distribution of lifespan. Though 70% of human lifespan variance remains unexplained by heritable factors, little is known about the intrinsic sources of physiologic heterogeneity in aging. To understand how complex physiologic networks generate lifespan variation, new methods are needed. Here, we present Asynch-seq, an approach that uses gene-expression heterogeneity within isogenic populations to study the processes generating lifespan variation. By collecting thousands of single-individual transcriptomes, we capture the Caenorhabditis elegans "pan-transcriptome"-a highly resolved atlas of non-genetic variation. We use our atlas to guide a large-scale perturbation screen that identifies the decoupling of total mRNA content between germline and soma as the largest source of physiologic heterogeneity in aging, driven by pleiotropic genes whose knockdown dramatically reduces lifespan variance. Our work demonstrates how systematic mapping of physiologic heterogeneity can be applied to reduce inter-individual disparities in aging., Competing Interests: Declaration of interests H.H. is co-founder of Omniscope and scientific advisory board member of MiRXES. C.M. is scientific consultant member of GLG., (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
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