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Prepublication data sharing (2009)

E. Birney ; T. J. Hudson ; E. D. Green ; [et al.]

Nature Publishing Group (NPG)

In: Nature. 461(7261): 168-70. doi: 10.1038/461168a.

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Publication Date: 2009-09-11

Description: Rapid release of prepublication data has served the field of genomics well. Attendees at a workshop in Toronto recommend extending the practice to other biological data sets.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3073843/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3073843/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Toronto International Data Release Workshop Authors -- Birney, Ewan -- Hudson, Thomas J -- Green, Eric D -- Gunter, Chris -- Eddy, Sean -- Rogers, Jane -- Harris, Jennifer R -- Ehrlich, S Dusko -- Apweiler, Rolf -- Austin, Christopher P -- Berglund, Lisa -- Bobrow, Martin -- Bountra, Chas -- Brookes, Anthony J -- Cambon-Thomsen, Anne -- Carter, Nigel P -- Chisholm, Rex L -- Contreras, Jorge L -- Cooke, Robert M -- Crosby, William L -- Dewar, Ken -- Durbin, Richard -- Dyke, Stephanie O M -- Ecker, Joseph R -- El Emam, Khaled -- Feuk, Lars -- Gabriel, Stacey B -- Gallacher, John -- Gelbart, William M -- Granell, Antoni -- Guarner, Francisco -- Hubbard, Tim -- Jackson, Scott A -- Jennings, Jennifer L -- Joly, Yann -- Jones, Steven M -- Kaye, Jane -- Kennedy, Karen L -- Knoppers, Bartha Maria -- Kyrpides, Nikos C -- Lowrance, William W -- Luo, Jingchu -- MacKay, John J -- Martin-Rivera, Luis -- McCombie, W Richard -- McPherson, John D -- Miller, Linda -- Miller, Webb -- Moerman, Don -- Mooser, Vincent -- Morton, Cynthia C -- Ostell, James M -- Ouellette, B F Francis -- Parkhill, Julian -- Raina, Parminder S -- Rawlings, Christopher -- Scherer, Steven E -- Scherer, Stephen W -- Schofield, Paul N -- Sensen, Christoph W -- Stodden, Victoria C -- Sussman, Michael R -- Tanaka, Toshihiro -- Thornton, Janet -- Tsunoda, Tatsuhiko -- Valle, David -- Vuorio, Eero I -- Walker, Neil M -- Wallace, Susan -- Weinstock, George -- Whitman, William B -- Worley, Kim C -- Wu, Cathy -- Wu, Jiayan -- Yu, Jun -- 062023/Wellcome Trust/United Kingdom -- 077198/Wellcome Trust/United Kingdom -- U54 HG003273/HG/NHGRI NIH HHS/ -- U54 HG003273-04/HG/NHGRI NIH HHS/ -- U54 HG003273-04S1/HG/NHGRI NIH HHS/ -- U54 HG003273-05/HG/NHGRI NIH HHS/ -- U54 HG003273-05S1/HG/NHGRI NIH HHS/ -- U54 HG003273-05S2/HG/NHGRI NIH HHS/ -- U54 HG003273-06/HG/NHGRI NIH HHS/ -- U54 HG003273-06S1/HG/NHGRI NIH HHS/ -- U54 HG003273-06S2/HG/NHGRI NIH HHS/ -- U54 HG003273-07/HG/NHGRI NIH HHS/ -- U54 HG003273-08/HG/NHGRI NIH HHS/ -- Biotechnology and Biological Sciences Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2009 Sep 10;461(7261):168-70. doi: 10.1038/461168a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19741685" target="_blank"〉PubMed〈/a〉

Keywords: *Access to Information ; Cooperative Behavior ; *Guidelines as Topic ; Human Genome Project ; Humans ; Ontario ; *Publishing/ethics/standards ; *Research/standards ; Research Personnel/ethics/standards

Print ISSN: 0028-0836

Electronic ISSN: 1476-4687

Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics

Published by Nature Publishing Group (NPG)

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International network of cancer genome projects (2010)

T. J. Hudson ; W. Anderson ; A. Artez ; [et al.]

Nature Publishing Group (NPG)

In: Nature. 464(7291): 993-8. doi: 10.1038/nature08987.

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Publication Date: 2010-04-16

Description: The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2902243/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2902243/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉International Cancer Genome Consortium -- Hudson, Thomas J -- Anderson, Warwick -- Artez, Axel -- Barker, Anna D -- Bell, Cindy -- Bernabe, Rosa R -- Bhan, M K -- Calvo, Fabien -- Eerola, Iiro -- Gerhard, Daniela S -- Guttmacher, Alan -- Guyer, Mark -- Hemsley, Fiona M -- Jennings, Jennifer L -- Kerr, David -- Klatt, Peter -- Kolar, Patrik -- Kusada, Jun -- Lane, David P -- Laplace, Frank -- Youyong, Lu -- Nettekoven, Gerd -- Ozenberger, Brad -- Peterson, Jane -- Rao, T S -- Remacle, Jacques -- Schafer, Alan J -- Shibata, Tatsuhiro -- Stratton, Michael R -- Vockley, Joseph G -- Watanabe, Koichi -- Yang, Huanming -- Yuen, Matthew M F -- Knoppers, Bartha M -- Bobrow, Martin -- Cambon-Thomsen, Anne -- Dressler, Lynn G -- Dyke, Stephanie O M -- Joly, Yann -- Kato, Kazuto -- Kennedy, Karen L -- Nicolas, Pilar -- Parker, Michael J -- Rial-Sebbag, Emmanuelle -- Romeo-Casabona, Carlos M -- Shaw, Kenna M -- Wallace, Susan -- Wiesner, Georgia L -- Zeps, Nikolajs -- Lichter, Peter -- Biankin, Andrew V -- Chabannon, Christian -- Chin, Lynda -- Clement, Bruno -- de Alava, Enrique -- Degos, Francoise -- Ferguson, Martin L -- Geary, Peter -- Hayes, D Neil -- Johns, Amber L -- Kasprzyk, Arek -- Nakagawa, Hidewaki -- Penny, Robert -- Piris, Miguel A -- Sarin, Rajiv -- Scarpa, Aldo -- van de Vijver, Marc -- Futreal, P Andrew -- Aburatani, Hiroyuki -- Bayes, Monica -- Botwell, David D L -- Campbell, Peter J -- Estivill, Xavier -- Grimmond, Sean M -- Gut, Ivo -- Hirst, Martin -- Lopez-Otin, Carlos -- Majumder, Partha -- Marra, Marco -- McPherson, John D -- Ning, Zemin -- Puente, Xose S -- Ruan, Yijun -- Stunnenberg, Hendrik G -- Swerdlow, Harold -- Velculescu, Victor E -- Wilson, Richard K -- Xue, Hong H -- Yang, Liu -- Spellman, Paul T -- Bader, Gary D -- Boutros, Paul C -- Flicek, Paul -- Getz, Gad -- Guigo, Roderic -- Guo, Guangwu -- Haussler, David -- Heath, Simon -- Hubbard, Tim J -- Jiang, Tao -- Jones, Steven M -- Li, Qibin -- Lopez-Bigas, Nuria -- Luo, Ruibang -- Muthuswamy, Lakshmi -- Ouellette, B F Francis -- Pearson, John V -- Quesada, Victor -- Raphael, Benjamin J -- Sander, Chris -- Speed, Terence P -- Stein, Lincoln D -- Stuart, Joshua M -- Teague, Jon W -- Totoki, Yasushi -- Tsunoda, Tatsuhiko -- Valencia, Alfonso -- Wheeler, David A -- Wu, Honglong -- Zhao, Shancen -- Zhou, Guangyu -- Lathrop, Mark -- Thomas, Gilles -- Yoshida, Teruhiko -- Axton, Myles -- Gunter, Chris -- Miller, Linda J -- Zhang, Junjun -- Haider, Syed A -- Wang, Jianxin -- Yung, Christina K -- Cros, Anthony -- Liang, Yong -- Gnaneshan, Saravanamuttu -- Guberman, Jonathan -- Hsu, Jack -- Chalmers, Don R C -- Hasel, Karl W -- Kaan, Terry S H -- Lowrance, William W -- Masui, Tohru -- Rodriguez, Laura Lyman -- Vergely, Catherine -- Bowtell, David D L -- Cloonan, Nicole -- deFazio, Anna -- Eshleman, James R -- Etemadmoghadam, Dariush -- Gardiner, Brooke B -- Kench, James G -- Sutherland, Robert L -- Tempero, Margaret A -- Waddell, Nicola J -- Wilson, Peter J -- Gallinger, Steve -- Tsao, Ming-Sound -- Shaw, Patricia A -- Petersen, Gloria M -- Mukhopadhyay, Debabrata -- DePinho, Ronald A -- Thayer, Sarah -- Shazand, Kamran -- Beck, Timothy -- Sam, Michelle -- Timms, Lee -- Ballin, Vanessa -- Lu, Youyong -- Ji, Jiafu -- Zhang, Xiuqing -- Chen, Feng -- Hu, Xueda -- Yang, Qi -- Tian, Geng -- Zhang, Lianhai -- Xing, Xiaofang -- Li, Xianghong -- Zhu, Zhenggang -- Yu, Yingyan -- Yu, Jun -- Tost, Jorg -- Brennan, Paul -- Holcatova, Ivana -- Zaridze, David -- Brazma, Alvis -- Egevard, Lars -- Prokhortchouk, Egor -- Banks, Rosamonde Elizabeth -- Uhlen, Mathias -- Viksna, Juris -- Ponten, Fredrik -- Skryabin, Konstantin -- Birney, Ewan -- Borg, Ake -- Borresen-Dale, Anne-Lise -- Caldas, Carlos -- Foekens, John A -- Martin, Sancha -- Reis-Filho, Jorge S -- Richardson, Andrea L -- Sotiriou, Christos -- Thoms, Giles -- van't Veer, Laura -- Birnbaum, Daniel -- Blanche, Helene -- Boucher, Pascal -- Boyault, Sandrine -- Masson-Jacquemier, Jocelyne D -- Pauporte, Iris -- Pivot, Xavier -- Vincent-Salomon, Anne -- Tabone, Eric -- Theillet, Charles -- Treilleux, Isabelle -- Bioulac-Sage, Paulette -- Decaens, Thomas -- Franco, Dominique -- Gut, Marta -- Samuel, Didier -- Zucman-Rossi, Jessica -- Eils, Roland -- Brors, Benedikt -- Korbel, Jan O -- Korshunov, Andrey -- Landgraf, Pablo -- Lehrach, Hans -- Pfister, Stefan -- Radlwimmer, Bernhard -- Reifenberger, Guido -- Taylor, Michael D -- von Kalle, Christof -- Majumder, Partha P -- Pederzoli, Paolo -- Lawlor, Rita A -- Delledonne, Massimo -- Bardelli, Alberto -- Gress, Thomas -- Klimstra, David -- Zamboni, Giuseppe -- Nakamura, Yusuke -- Miyano, Satoru -- Fujimoto, Akihiro -- Campo, Elias -- de Sanjose, Silvia -- Montserrat, Emili -- Gonzalez-Diaz, Marcos -- Jares, Pedro -- Himmelbauer, Heinz -- Bea, Silvia -- Aparicio, Samuel -- Easton, Douglas F -- Collins, Francis S -- Compton, Carolyn C -- Lander, Eric S -- Burke, Wylie -- Green, Anthony R -- Hamilton, Stanley R -- Kallioniemi, Olli P -- Ley, Timothy J -- Liu, Edison T -- Wainwright, Brandon J -- 077198/Wellcome Trust/United Kingdom -- 088340/Wellcome Trust/United Kingdom -- 093867/Wellcome Trust/United Kingdom -- 6613/Cancer Research UK/United Kingdom -- K08 DK071329/DK/NIDDK NIH HHS/ -- K08 DK071329-04/DK/NIDDK NIH HHS/ -- K08 DK071329-05/DK/NIDDK NIH HHS/ -- P01 CA117969/CA/NCI NIH HHS/ -- P01 CA117969-04S1/CA/NCI NIH HHS/ -- P01 CA117969-05/CA/NCI NIH HHS/ -- P50 CA102701/CA/NCI NIH HHS/ -- P50 CA102701-08/CA/NCI NIH HHS/ -- P50 CA127003/CA/NCI NIH HHS/ -- P50 CA127003-04/CA/NCI NIH HHS/ -- P50 CA127003-05/CA/NCI NIH HHS/ -- R01 HG001806-02/HG/NHGRI NIH HHS/ -- England -- Nature. 2010 Apr 15;464(7291):993-8. doi: 10.1038/nature08987.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20393554" target="_blank"〉PubMed〈/a〉

Keywords: DNA Methylation ; DNA Mutational Analysis/trends ; Databases, Genetic ; Genes, Neoplasm/genetics ; Genetics, Medical/*organization & administration/trends ; Genome, Human/*genetics ; Genomics/*organization & administration/trends ; Humans ; Intellectual Property ; *International Cooperation ; Mutation ; Neoplasms/classification/*genetics/pathology/therapy

Print ISSN: 0028-0836

Electronic ISSN: 1476-4687

Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics

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In silico genetics: identification of a functional element regulating H2-Ealpha gene expression (2004)

G. Liao ; J. Wang ; J. Guo ; [et al.]

American Association for the Advancement of Science (AAAS)

In: Science. 306(5696): 690-5. doi: 10.1126/science.1100636.

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Publication Date: 2004-10-23

Description: Computational tools can markedly accelerate the rate at which murine genetic models can be analyzed. We developed a computational method for mapping phenotypic traits that vary among inbred strains onto haplotypic blocks. This method correctly predicted the genetic basis for strain-specific differences in several biologically important traits. It was also used to identify an allele-specific functional genomic element regulating H2-Ealpha gene expression. This functional element, which contained the binding sites for YY1 and a second transcription factor that is probably serum response factor, is located within the first intron of the H2-Ealpha gene. This computational method will greatly improve our ability to identify the genetic basis for a variety of phenotypic traits, ranging from qualitative trait information to quantitative gene expression data, which vary among inbred mouse strains.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Liao, Guochun -- Wang, Jianmei -- Guo, Jingshu -- Allard, John -- Cheng, Janet -- Ng, Anh -- Shafer, Steve -- Puech, Anne -- McPherson, John D -- Foernzler, Dorothee -- Peltz, Gary -- Usuka, Jonathan -- 1 R01 HG02322-01/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2004 Oct 22;306(5696):690-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics and Genomics, Roche Palo Alto, 3431 Hillview Avenue, Palo Alto, CA 94304-1397, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15499019" target="_blank"〉PubMed〈/a〉

Keywords: Alleles ; Animals ; Binding Sites ; *Computational Biology ; Electrophoretic Mobility Shift Assay ; Gene Expression Profiling ; *Gene Expression Regulation ; Genes, MHC Class II ; Genetic Variation ; H-2 Antigens/*genetics ; Haplotypes ; Hydrocarbons, Aromatic/pharmacology ; Introns ; Liver/metabolism ; Lung/metabolism ; Major Histocompatibility Complex ; Mice ; Mice, Inbred Strains ; Oligodeoxyribonucleotides/metabolism ; Oligonucleotide Array Sequence Analysis ; Phenotype ; Polymorphism, Single Nucleotide ; Receptors, Aryl Hydrocarbon/chemistry/genetics/metabolism ; Regulatory Sequences, Nucleic Acid ; Serum Response Factor/metabolism ; Transcription Factors/metabolism

Print ISSN: 0036-8075

Electronic ISSN: 1095-9203

Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics

Published by American Association for the Advancement of Science (AAAS)

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Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes (2012)

A. V. Biankin ; N. Waddell ; K. S. Kassahn ; [et al.]

Nature Publishing Group (NPG)

In: Nature. 491(7424): 399-405. doi: 10.1038/nature11547.

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Publication Date: 2012-10-30

Description: Pancreatic cancer is a highly lethal malignancy with few effective therapies. We performed exome sequencing and copy number analysis to define genomic aberrations in a prospectively accrued clinical cohort (n = 142) of early (stage I and II) sporadic pancreatic ductal adenocarcinoma. Detailed analysis of 99 informative tumours identified substantial heterogeneity with 2,016 non-silent mutations and 1,628 copy-number variations. We define 16 significantly mutated genes, reaffirming known mutations (KRAS, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1), and uncover novel mutated genes including additional genes involved in chromatin modification (EPC1 and ARID2), DNA damage repair (ATM) and other mechanisms (ZIM2, MAP2K4, NALCN, SLC16A4 and MAGEA6). Integrative analysis with in vitro functional data and animal models provided supportive evidence for potential roles for these genetic aberrations in carcinogenesis. Pathway-based analysis of recurrently mutated genes recapitulated clustering in core signalling pathways in pancreatic ductal adenocarcinoma, and identified new mutated genes in each pathway. We also identified frequent and diverse somatic aberrations in genes described traditionally as embryonic regulators of axon guidance, particularly SLIT/ROBO signalling, which was also evident in murine Sleeping Beauty transposon-mediated somatic mutagenesis models of pancreatic cancer, providing further supportive evidence for the potential involvement of axon guidance genes in pancreatic carcinogenesis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3530898/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3530898/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Biankin, Andrew V -- Waddell, Nicola -- Kassahn, Karin S -- Gingras, Marie-Claude -- Muthuswamy, Lakshmi B -- Johns, Amber L -- Miller, David K -- Wilson, Peter J -- Patch, Ann-Marie -- Wu, Jianmin -- Chang, David K -- Cowley, Mark J -- Gardiner, Brooke B -- Song, Sarah -- Harliwong, Ivon -- Idrisoglu, Senel -- Nourse, Craig -- Nourbakhsh, Ehsan -- Manning, Suzanne -- Wani, Shivangi -- Gongora, Milena -- Pajic, Marina -- Scarlett, Christopher J -- Gill, Anthony J -- Pinho, Andreia V -- Rooman, Ilse -- Anderson, Matthew -- Holmes, Oliver -- Leonard, Conrad -- Taylor, Darrin -- Wood, Scott -- Xu, Qinying -- Nones, Katia -- Fink, J Lynn -- Christ, Angelika -- Bruxner, Tim -- Cloonan, Nicole -- Kolle, Gabriel -- Newell, Felicity -- Pinese, Mark -- Mead, R Scott -- Humphris, Jeremy L -- Kaplan, Warren -- Jones, Marc D -- Colvin, Emily K -- Nagrial, Adnan M -- Humphrey, Emily S -- Chou, Angela -- Chin, Venessa T -- Chantrill, Lorraine A -- Mawson, Amanda -- Samra, Jaswinder S -- Kench, James G -- Lovell, Jessica A -- Daly, Roger J -- Merrett, Neil D -- Toon, Christopher -- Epari, Krishna -- Nguyen, Nam Q -- Barbour, Andrew -- Zeps, Nikolajs -- Australian Pancreatic Cancer Genome Initiative -- Kakkar, Nipun -- Zhao, Fengmei -- Wu, Yuan Qing -- Wang, Min -- Muzny, Donna M -- Fisher, William E -- Brunicardi, F Charles -- Hodges, Sally E -- Reid, Jeffrey G -- Drummond, Jennifer -- Chang, Kyle -- Han, Yi -- Lewis, Lora R -- Dinh, Huyen -- Buhay, Christian J -- Beck, Timothy -- Timms, Lee -- Sam, Michelle -- Begley, Kimberly -- Brown, Andrew -- Pai, Deepa -- Panchal, Ami -- Buchner, Nicholas -- De Borja, Richard -- Denroche, Robert E -- Yung, Christina K -- Serra, Stefano -- Onetto, Nicole -- Mukhopadhyay, Debabrata -- Tsao, Ming-Sound -- Shaw, Patricia A -- Petersen, Gloria M -- Gallinger, Steven -- Hruban, Ralph H -- Maitra, Anirban -- Iacobuzio-Donahue, Christine A -- Schulick, Richard D -- Wolfgang, Christopher L -- Morgan, Richard A -- Lawlor, Rita T -- Capelli, Paola -- Corbo, Vincenzo -- Scardoni, Maria -- Tortora, Giampaolo -- Tempero, Margaret A -- Mann, Karen M -- Jenkins, Nancy A -- Perez-Mancera, Pedro A -- Adams, David J -- Largaespada, David A -- Wessels, Lodewyk F A -- Rust, Alistair G -- Stein, Lincoln D -- Tuveson, David A -- Copeland, Neal G -- Musgrove, Elizabeth A -- Scarpa, Aldo -- Eshleman, James R -- Hudson, Thomas J -- Sutherland, Robert L -- Wheeler, David A -- Pearson, John V -- McPherson, John D -- Gibbs, Richard A -- Grimmond, Sean M -- 13031/Cancer Research UK/United Kingdom -- 2P50CA101955/CA/NCI NIH HHS/ -- P01CA134292/CA/NCI NIH HHS/ -- P50 CA101955/CA/NCI NIH HHS/ -- P50 CA102701/CA/NCI NIH HHS/ -- P50CA062924/CA/NCI NIH HHS/ -- R01 CA097075/CA/NCI NIH HHS/ -- R01 CA97075/CA/NCI NIH HHS/ -- U54 HG003273/HG/NHGRI NIH HHS/ -- Cancer Research UK/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2012 Nov 15;491(7424):399-405. doi: 10.1038/nature11547. Epub 2012 Oct 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Kinghorn Cancer Centre, 370 Victoria Street, Darlinghurst, Sydney, New South Wales 2010, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23103869" target="_blank"〉PubMed〈/a〉

Keywords: Animals ; Axons/*metabolism ; Carcinoma, Pancreatic Ductal/*genetics/*pathology ; Gene Dosage ; Gene Expression Regulation, Neoplastic ; Genome/*genetics ; Humans ; Kaplan-Meier Estimate ; Mice ; Mutation ; Pancreatic Neoplasms/*genetics/*pathology ; Proteins/genetics ; Signal Transduction

Print ISSN: 0028-0836

Electronic ISSN: 1476-4687

Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics

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Identification of pre-leukaemic haematopoietic stem cells in acute leukaemia (2014)

L. I. Shlush ; S. Zandi ; A. Mitchell ; [et al.]

Nature Publishing Group (NPG)

In: Nature. 506(7488): 328-33. doi: 10.1038/nature13038.

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Publication Date: 2014-02-14

Description: In acute myeloid leukaemia (AML), the cell of origin, nature and biological consequences of initiating lesions, and order of subsequent mutations remain poorly understood, as AML is typically diagnosed without observation of a pre-leukaemic phase. Here, highly purified haematopoietic stem cells (HSCs), progenitor and mature cell fractions from the blood of AML patients were found to contain recurrent DNMT3A mutations (DNMT3A(mut)) at high allele frequency, but without coincident NPM1 mutations (NPM1c) present in AML blasts. DNMT3A(mut)-bearing HSCs showed a multilineage repopulation advantage over non-mutated HSCs in xenografts, establishing their identity as pre-leukaemic HSCs. Pre-leukaemic HSCs were found in remission samples, indicating that they survive chemotherapy. Therefore DNMT3A(mut) arises early in AML evolution, probably in HSCs, leading to a clonally expanded pool of pre-leukaemic HSCs from which AML evolves. Our findings provide a paradigm for the detection and treatment of pre-leukaemic clones before the acquisition of additional genetic lesions engenders greater therapeutic resistance.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shlush, Liran I -- Zandi, Sasan -- Mitchell, Amanda -- Chen, Weihsu Claire -- Brandwein, Joseph M -- Gupta, Vikas -- Kennedy, James A -- Schimmer, Aaron D -- Schuh, Andre C -- Yee, Karen W -- McLeod, Jessica L -- Doedens, Monica -- Medeiros, Jessie J F -- Marke, Rene -- Kim, Hyeoung Joon -- Lee, Kwon -- McPherson, John D -- Hudson, Thomas J -- HALT Pan-Leukemia Gene Panel Consortium -- Brown, Andrew M K -- Yousif, Fouad -- Trinh, Quang M -- Stein, Lincoln D -- Minden, Mark D -- Wang, Jean C Y -- Dick, John E -- CSC-105367/Canadian Institutes of Health Research/Canada -- R21 CA152613/CA/NCI NIH HHS/ -- England -- Nature. 2014 Feb 20;506(7488):328-33. doi: 10.1038/nature13038. Epub 2014 Feb 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, Ontario M5G 2M9, Canada [2]. ; Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, Ontario M5G 2M9, Canada. ; 1] Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, Ontario M5G 2M9, Canada [2] Department of Medicine, University of Toronto, Toronto, Ontario M5S 2J7, Canada [3] Division of Medical Oncology and Hematology, UHN, Toronto, Ontario M5G 2M9, Canada. ; 1] Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, Ontario M5G 2M9, Canada [2] Department of Medicine, University of Toronto, Toronto, Ontario M5S 2J7, Canada [3] Division of Medical Oncology and Hematology, UHN, Toronto, Ontario M5G 2M9, Canada [4] Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 2M9, Canada. ; 1] Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, Ontario M5G 2M9, Canada [2] Radboud University, Nijmegen Medical Centre, Nijmegen 6500 HB, The Netherlands. ; Chonnam National University Hwasun Hospital, Genome Research Center for Hematopoietic Diseases, Gwangju 519-809, South Korea. ; 1] Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 2M9, Canada [2] Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada. ; 1] Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 2M9, Canada [2] Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada [3] Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada. ; Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada. ; 1] Ontario Institute for Cancer Research, Toronto, Ontario M5G 0A3, Canada [2] Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada. ; 1] Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, Ontario M5G 2M9, Canada [2] Department of Molecular Genetics, University of Toronto, Toronto, Ontario M5S 1A8, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24522528" target="_blank"〉PubMed〈/a〉

Keywords: Animals ; Cell Differentiation ; Cell Division ; Cell Lineage ; Clone Cells/cytology/metabolism/pathology ; DNA (Cytosine-5-)-Methyltransferase/genetics/metabolism ; Drug Resistance, Neoplasm/drug effects ; Female ; Hematopoiesis ; Hematopoietic Stem Cells/*cytology/drug effects/metabolism/pathology ; Heterografts ; Humans ; Isocitrate Dehydrogenase/genetics ; Leukemia, Myeloid, Acute/diagnosis/drug therapy/genetics/*pathology ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Mutation/genetics ; Neoplasm Transplantation ; Neoplastic Stem Cells/*cytology/drug effects/metabolism/pathology ; Nuclear Proteins/genetics ; Remission Induction ; T-Lymphocytes/metabolism/pathology

Print ISSN: 0028-0836

Electronic ISSN: 1476-4687

Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics

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Distinct routes of lineage development reshape the human blood hierarchy across ontogeny (2015)

F. Notta ; S. Zandi ; N. Takayama ; [et al.]

American Association for the Advancement of Science (AAAS)

In: Science. 351(6269): aab2116. doi: 10.1126/science.aab2116.

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Publication Date: 2015-11-07

Description: In a classical view of hematopoiesis, the various blood cell lineages arise via a hierarchical scheme starting with multipotent stem cells that become increasingly restricted in their differentiation potential through oligopotent and then unipotent progenitors. We developed a cell-sorting scheme to resolve myeloid (My), erythroid (Er), and megakaryocytic (Mk) fates from single CD34(+) cells and then mapped the progenitor hierarchy across human development. Fetal liver contained large numbers of distinct oligopotent progenitors with intermingled My, Er, and Mk fates. However, few oligopotent progenitor intermediates were present in the adult bone marrow. Instead, only two progenitor classes predominate, multipotent and unipotent, with Er-Mk lineages emerging from multipotent cells. The developmental shift to an adult "two-tier" hierarchy challenges current dogma and provides a revised framework to understand normal and disease states of human hematopoiesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Notta, Faiyaz -- Zandi, Sasan -- Takayama, Naoya -- Dobson, Stephanie -- Gan, Olga I -- Wilson, Gavin -- Kaufmann, Kerstin B -- McLeod, Jessica -- Laurenti, Elisa -- Dunant, Cyrille F -- McPherson, John D -- Stein, Lincoln D -- Dror, Yigal -- Dick, John E -- Canadian Institutes of Health Research/Canada -- Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2016 Jan 8;351(6269):aab2116. doi: 10.1126/science.aab2116. Epub 2015 Nov 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada. Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada. ; Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada. ; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada. Ontario Institute for Cancer Research, Toronto, Ontario, Canada. ; Wellcome Trust, Medical Research Council Cambridge Stem Cell Institute, Department of Haematology, University of Cambridge, Cambridge, UK. ; Ecole Polytechnique Federale de Lausanne, LMC, Station 12, Lausanne, CH-1015, Switzerland. ; Medical Biophysics, University of Toronto, Toronto, Ontario, Canada. Ontario Institute for Cancer Research, Toronto, Ontario, Canada. ; The Hospital for Sick Children Research Institute, University of Toronto, Ontario, Canada. ; Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada. Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada. jdick@uhnres.utoronto.ca.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26541609" target="_blank"〉PubMed〈/a〉

Keywords: Adult ; Antigens, CD34/analysis ; Cell Lineage/genetics/*physiology ; Cell Separation ; Cells, Cultured ; Erythroid Cells/*cytology ; Fetal Blood/cytology ; Gene Expression Profiling ; Hematopoiesis/genetics/*physiology ; Humans ; Liver/cytology/embryology ; Megakaryocyte Progenitor Cells/*cytology ; Megakaryocytes/*cytology ; Multipotent Stem Cells/cytology ; Myeloid Cells/*cytology ; Transcription, Genetic

Print ISSN: 0036-8075

Electronic ISSN: 1095-9203

Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics

Published by American Association for the Advancement of Science (AAAS)

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Optimization of miRNA-seq data preprocessing (2015)

Tam, S., Tsao, M.-S., McPherson, J. D.

Oxford University Press

In: Briefings in Bioinformatics

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Publication Date: 2015-11-20

Description: The past two decades of microRNA (miRNA) research has solidified the role of these small non-coding RNAs as key regulators of many biological processes and promising biomarkers for disease. The concurrent development in high-throughput profiling technology has further advanced our understanding of the impact of their dysregulation on a global scale. Currently, next-generation sequencing is the platform of choice for the discovery and quantification of miRNAs. Despite this, there is no clear consensus on how the data should be preprocessed before conducting downstream analyses. Often overlooked, data preprocessing is an essential step in data analysis: the presence of unreliable features and noise can affect the conclusions drawn from downstream analyses. Using a spike-in dilution study, we evaluated the effects of several general-purpose aligners (BWA, Bowtie, Bowtie 2 and Novoalign), and normalization methods (counts-per-million, total count scaling, upper quartile scaling, Trimmed Mean of M, DESeq, linear regression, cyclic loess and quantile) with respect to the final miRNA count data distribution, variance, bias and accuracy of differential expression analysis. We make practical recommendations on the optimal preprocessing methods for the extraction and interpretation of miRNA count data from small RNA-sequencing experiments.

Print ISSN: 1467-5463

Electronic ISSN: 1477-4054

Topics: Biology , Computer Science

Published by Oxford University Press

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