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| March 2016 Volume 48, Issue 3 |  | | |  |  Editorial
Correspondence
News and Views
Analysis
Articles
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Advertisement | | The Geoffrey Beene Cancer Research Center at Memorial Sloan Kettering Cancer Center, Nature, Nature Cell Biology and Nature Reviews Cancer present:
CANCER AS AN EVOLVING AND SYSTEMIC DISEASE
March 12-15, 2016 | New York, NY, USA
REGISTER NOW! |  | | | | | | Editorial |  Top | |  | | Peer review in the cloud p223
doi:10.1038/ng.3524
The migration of cancer genomics data to cloud computing is a great encouragement for data reuse and integration by bioinformaticians and other data symbionts. Because the cloud allows rapid, transparent and reproducible research on large data sets, we are keen to consider articles and analyses submitted to the journal that provide peer referee access to their constituent cloud projects. | | Correspondence | Top | | | | Analysis of five years of controlled access and data sharing compliance at the International Cancer Genome Consortium pp224 - 225
Yann Joly, Emilie de Vries-Seguin, Don Chalmers, B F Francis Ouellette, Joseph Yamada, Martin Bobrow & Bartha M Knoppers for the ICGC Data Access Compliance Office and the ICGC International Data Access Committee
doi:10.1038/ng.3499 | | News and Views | Top | | | | | | Analysis | Top | | | | Genes with monoallelic expression contribute disproportionately to genetic diversity in humans pp231 - 237
Virginia Savova, Sung Chun, Mashaal Sohail, Ruth B McCole, Robert Witwicki, Lisa Gai, Tobias L Lenz, C-ting Wu, Shamil R Sunyaev & Alexander A Gimelbrant
doi:10.1038/ng.3493
Shamil Sunyaev, Alexander Gimelbrant and colleagues report an analysis of the genetic variability in human monoallelically expressed genes. They find that genes with monoallelic expression show greater genetic diversity than biallelically expressed genes and that this diversity is associated with greater allelic age. | | | | Identification of neutral tumor evolution across cancer types pp238 - 244
Marc J Williams, Benjamin Werner, Chris P Barnes, Trevor A Graham & Andrea Sottoriva
doi:10.1038/ng.3489
Andrea Sottoriva, Trevor Graham and colleagues analyze tumor sequencing data and show that a substantial proportion of cancers of many different types are characterized by neutral evolution resulting in a characteristic power-law distribution of the mutant allele frequencies. This neutral framework provides a new way to interpret cancer genomic data and to discriminate between functional and non-functional intratumoral heterogeneity. | | Articles | Top | | | | Integrative approaches for large-scale transcriptome-wide association studies pp245 - 252
Alexander Gusev, Arthur Ko, Huwenbo Shi, Gaurav Bhatia, Wonil Chung, Brenda W J H Penninx, Rick Jansen, Eco J C de Geus, Dorret I Boomsma, Fred A Wright, Patrick F Sullivan, Elina Nikkola, Marcus Alvarez, Mete Civelek, Aldons J Lusis, Terho Lehtimäki, Emma Raitoharju, Mika Kähönen, Ilkka Seppälä, Olli T Raitakari, Johanna Kuusisto, Markku Laakso, Alkes L Price, Päivi Pajukanta & Bogdan Pasaniuc
doi:10.1038/ng.3506
Alexander Gusev, Bogdan Pasaniuc and colleagues present a strategy that integrates gene expression measurements with summary statistics from large-scale genome-wide association studies to identify genes whose cis-regulated expression is associated with complex traits. They identify 69 new genes significantly associated with obesity-related traits and illustrate how this approach can provide insights into the genetic basis of complex traits. | | | | DNA methylation dynamics during B cell maturation underlie a continuum of disease phenotypes in chronic lymphocytic leukemia pp253 - 264
Christopher C Oakes, Marc Seifert, Yassen Assenov, Lei Gu, Martina Przekopowitz, Amy S Ruppert, Qi Wang, Charles D Imbusch, Andrius Serva, Sandra D Koser, David Brocks, Daniel B Lipka, Olga Bogatyrova, Dieter Weichenhan, Benedikt Brors, Laura Rassenti, Thomas J Kipps, Daniel Mertens, Marc Zapatka, Peter Lichter, Hartmut Döhner, Ralf Küppers, Thorsten Zenz, Stephan Stilgenbauer, John C Byrd & Christoph Plass
doi:10.1038/ng.3488
Christoph Plass, Christopher Oakes and colleagues study genome-wide DNA methylation dynamics during B cell maturation and the pathogenic role of transcription factor dysregulation in chronic lymphocytic leukemia (CLL). By comparing normal and malignant B cells, they find that tumors derive from a continuum of maturation states, which correlate with different clinical outcomes. | | | | An oncogenic MYB feedback loop drives alternate cell fates in adenoid cystic carcinoma pp265 - 272
Yotam Drier, Matthew J Cotton, Kaylyn E Williamson, Shawn M Gillespie, Russell J H Ryan, Michael J Kluk, Christopher D Carey, Scott J Rodig, Lynette M Sholl, Amir H Afrogheh, William C Faquin, Lurdes Queimado, Jun Qi, Michael J Wick, Adel K El-Naggar, James E Bradner, Christopher A Moskaluk, Jon C Aster, Birgit Knoechel & Bradley E Bernstein
doi:10.1038/ng.3502
Bradley Bernstein, Birgit Knoechel and colleagues identify super-enhancer translocations that drive overexpression of MYB in adenoid cystic carcinoma (ACC). They find that MYB binds to the translocated enhancers and to other active enhancers that drive different regulatory programs in alternate cell lineages in ACC. | | | | MYB-QKI rearrangements in angiocentric glioma drive tumorigenicity through a tripartite mechanism pp273 - 282
Pratiti Bandopadhayay, Lori A Ramkissoon, Payal Jain, Guillaume Bergthold, Jeremiah Wala, Rhamy Zeid, Steven E Schumacher, Laura Urbanski, Ryan O'Rourke, William J Gibson, Kristine Pelton, Shakti H Ramkissoon, Harry J Han, Yuankun Zhu, Namrata Choudhari, Amanda Silva, Katie Boucher, Rosemary E Henn, Yun Jee Kang, David Knoff, Brenton R Paolella, Adrianne Gladden-Young, Pascale Varlet, Melanie Pages, Peleg M Horowitz, Alexander Federation, Hayley Malkin, Adam A Tracy, Sara Seepo, Matthew Ducar, Paul Van Hummelen, Mariarita Santi, Anna Maria Buccoliero, Mirko Scagnet, Daniel C Bowers, Caterina Giannini, Stephanie Puget, Cynthia Hawkins, Uri Tabori, Almos Klekner, Laszlo Bognar, Peter C Burger, Charles Eberhart, Fausto J Rodriguez, D Ashley Hill, Sabine Mueller, Daphne A Haas-Kogan, Joanna J Phillips, Sandro Santagata, Charles D Stiles, James E Bradner, Nada Jabado, Alon Goren, Jacques Grill, Azra H Ligon, Liliana Goumnerova, Angela J Waanders, Phillip B Storm, Mark W Kieran, Keith L Ligon, Rameen Beroukhim & Adam C Resnick
doi:10.1038/ng.3500
Keith Ligon, Adam Resnick, Rameen Beroukhim and colleagues identify MYB-QKI fusions in angiocentric gliomas and show that these rearrangements promote tumorigenesis through activation of MYB by truncation, enhancer translocation driving aberrant MYB-QKI expression and hemizygous loss of QKI. | | | | Piwi maintains germline stem cells and oogenesis in Drosophila through negative regulation of Polycomb group proteins pp283 - 291
Jamy C Peng, Anton Valouev, Na Liu & Haifan Lin
doi:10.1038/ng.3486
Haifan Lin, Jamy Peng and colleagues report that the Drosophila Piwi protein is a negative regulator of PRC2 in the fly ovary, a function required for the maintenance of germline stem cells. Their results indicate that Piwi sequesters PRC2 in the nucleoplasm, thereby reducing genome-wide levels of H3K27me3. | | | | Quantitatively predictable control of Drosophila transcriptional enhancers in vivo with engineered transcription factors pp292 - 298
Justin Crocker, Garth R Ilsley & David L Stern
doi:10.1038/ng.3509
Justin Crocker, Garth Ilsley and David Stern use engineered transcription factors to regulate enhancers in a quantitatively predictable manner in Drosophila embryos. Their models of enhancer function provide a framework for the quantitative control of enhancers in vivo. | | | | The genomic basis of parasitism in the Strongyloides clade of nematodes OPEN pp299 - 307
Vicky L Hunt, Isheng J Tsai, Avril Coghlan, Adam J Reid, Nancy Holroyd, Bernardo J Foth, Alan Tracey, James A Cotton, Eleanor J Stanley, Helen Beasley, Hayley M Bennett, Karen Brooks, Bhavana Harsha, Rei Kajitani, Arpita Kulkarni, Dorothee Harbecke, Eiji Nagayasu, Sarah Nichol, Yoshitoshi Ogura, Michael A Quail, Nadine Randle, Dong Xia, Norbert W Brattig, Hanns Soblik, Diogo M Ribeiro, Alejandro Sanchez-Flores, Tetsuya Hayashi, Takehiko Itoh, Dee R Denver, Warwick Grant, Jonathan D Stoltzfus, James B Lok, Haruhiko Murayama, Jonathan Wastling, Adrian Streit, Taisei Kikuchi, Mark Viney & Matthew Berriman
doi:10.1038/ng.3495
Taisei Kikuchi, Mark Viney, Matthew Berriman and colleagues report the genome sequences of six species of nematodes from the Strongyloides clade of nematodes, including human and animal pathogens, facultative parasites and a free-living species. They find that expansions of the astacin and SCP/TAPS gene families are associated with parasitism in these species. | | | | Uncovering Listeria monocytogenes hypervirulence by harnessing its biodiversity pp308 - 313
Mylène M Maury, Yu-Huan Tsai, Caroline Charlier, Marie Touchon, Viviane Chenal-Francisque, Alexandre Leclercq, Alexis Criscuolo, Charlotte Gaultier, Sophie Roussel, Anne Brisabois, Olivier Disson, Eduardo P C Rocha, Sylvain Brisse & Marc Lecuit
doi:10.1038/ng.3501
Marc Lecuit, Sylvain Brisse and colleagues combine Listeria monocytogenes population genomic data with human epidemiological and clinical data to study human listeriosis. They report new putative virulence factors and demonstrate that some clones are hypervirulent in a humanized mouse model of listeriosis and have enhanced neural and placental tropism.
See also: News and Views by Grad & Fortune | | Letters | Top | | | | Weighting sequence variants based on their annotation increases power of whole-genome association studies pp314 - 317
Gardar Sveinbjornsson, Anders Albrechtsen, Florian Zink, Sigurjón A Gudjonsson, Asmundur Oddson, Gísli Másson, Hilma Holm, Augustine Kong, Unnur Thorsteinsdottir, Patrick Sulem, Daniel F Gudbjartsson & Kari Stefansson
doi:10.1038/ng.3507
Daniel Gudbjartsson, Kari Stefansson and colleagues propose a new weighted Bonferroni approach for determining significance thresholds for human genome-wide association studies (GWAS). They demonstrate that the weighted approach, which is based on sequence annotation enrichments, improves power over standard GWAS methods. | | | | HLA class II sequence variants influence tuberculosis risk in populations of European ancestry pp318 - 322
Gardar Sveinbjornsson, Daniel F Gudbjartsson, Bjarni V Halldorsson, Karl G Kristinsson, Magnus Gottfredsson, Jeffrey C Barrett, Larus J Gudmundsson, Kai Blondal, Arnaldur Gylfason, Sigurjon Axel Gudjonsson, Hafdis T Helgadottir, Adalbjorg Jonasdottir, Aslaug Jonasdottir, Ari Karason, Ljiljana Bulat Kardum, Jelena Knežević, Helgi Kristjansson, Mar Kristjansson, Arthur Love, Yang Luo, Olafur T Magnusson, Patrick Sulem, Augustine Kong, Gisli Masson, Unnur Thorsteinsdottir, Zlatko Dembic, Sergey Nejentsev, Thorsteinn Blondal, Ingileif Jonsdottir & Kari Stefansson
doi:10.1038/ng.3498
Ingileif Jonsdottir, Kari Stefansson and colleagues show that variants in the HLA class II region contribute to tuberculosis risk in populations of European ancestry. They propose that the associated variants influence disease risk by altering expression of HLA class II molecules presenting protective M. tuberculosis antigens to T cells. | | | | High-density genotyping of immune-related loci identifies new SLE risk variants in individuals with Asian ancestry pp323 - 330
Celi Sun, Julio E Molineros, Loren L Looger, Xu-jie Zhou, Kwangwoo Kim, Yukinori Okada, Jianyang Ma, Yuan-yuan Qi, Xana Kim-Howard, Prasenjeet Motghare, Krishna Bhattarai, Adam Adler, So-Young Bang, Hye-Soon Lee, Tae-Hwan Kim, Young Mo Kang, Chang-Hee Suh, Won Tae Chung, Yong-Beom Park, Jung-Yoon Choe, Seung Cheol Shim, Yuta Kochi, Akari Suzuki, Michiaki Kubo, Takayuki Sumida, Kazuhiko Yamamoto, Shin-Seok Lee, Young Jin Kim, Bok-Ghee Han, Mikhail Dozmorov, Kenneth M Kaufman, Jonathan D Wren, John B Harley, Nan Shen, Kek Heng Chua, Hong Zhang, Sang-Cheol Bae & Swapan K Nath
doi:10.1038/ng.3496
Swapan Nath, Sang-Cheol Bae and colleagues report the results of a large-scale association study of systemic lupus erythematosus in individuals of Asian ancestry. They identify several new susceptibility loci and find enrichment for signals near genes implicated in B cell and T cell function. | | | | A predictive computational framework for direct reprogramming between human cell types pp331 - 335
Owen J L Rackham, Jaber Firas, Hai Fang, Matt E Oates, Melissa L Holmes, Anja S Knaupp, The FANTOM Consortium, Harukazu Suzuki, Christian M Nefzger, Carsten O Daub, Jay W Shin, Enrico Petretto, Alistair R R Forrest, Yoshihide Hayashizaki, Jose M Polo & Julian Gough
doi:10.1038/ng.3487
Owen Rackham, Jose Polo, Julian Gough and colleagues present a method, Mogrify, for predicting sets of transcription factors that can induce transdifferentiation between cell types. They show that Mogrify is able to predict known factors for published cell conversions and experimentally validate factors for two new conversions.
See also: News and Views by Cahan | | | | A single three-dimensional chromatin compartment in amphioxus indicates a stepwise evolution of vertebrate Hox bimodal regulation pp336 - 341
Rafael D Acemel, Juan J Tena, Ibai Irastorza-Azcarate, Ferdinand Marlétaz, Carlos Gómez-Marín, Elisa de la Calle-Mustienes, Stéphanie Bertrand, Sergio G Diaz, Daniel Aldea, Jean-Marc Aury, Sophie Mangenot, Peter W H Holland, Damien P Devos, Ignacio Maeso, Hector Escrivá & José Luis Gómez-Skarmeta
doi:10.1038/ng.3497
José Luis Gómez-Skarmeta, Hector Escriva, Ignacio Maeso, Damien Devos and colleagues perform 4C-seq profiling of the Hox cluster in amphioxus embryos and find that, unlike in vertebrate embryos, the cluster is organized into a single chromatin interaction domain. They suggest that the vertebrate Hox bipartite regulatory system is an evolutionary novelty.
See also: News and Views by Deschamps | | | Top | |  | | | | | | | Natureevents is a fully searchable, multi-disciplinary database designed to maximise exposure for events organisers. The contents of the Natureevents Directory are now live. The digital version is available here.
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