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Cell
This journal offers authors two options (open access or subscription) to publish research

Apr 15, 2021

Volume 184Issue 8p1941-2258
Open Archive
On the cover: The Global Microbiome Conservancy (GMbC) is an international non-profit initiative to preserve and characterize rapidly disappearing gut microbiome biodiversity worldwide. In this issue, Groussin and Poyet et al. show that industrialization profoundly impacts the genome and function of gut bacteria, with implications for antibiotic resistance and other major health concerns. They also reveal that the functions of transferred genes reflect host lifestyle. In the cover image, Hadza foragers rest by the fire under starlight after a long hunt. The remaining hunter-gatherer populations worldwide currently maintain the richest microbiome diversity, but their lifestyles are under significant pressure to change. Lake Eyasi, Tanzania. February 2018. Artist/image source: Christopher Corzett (corzett@usc.edu) for the Global Microbiome Conservancy....
On the cover: The Global Microbiome Conservancy (GMbC) is an international non-profit initiative to preserve and characterize rapidly disappearing gut microbiome biodiversity worldwide. In this issue, Groussin and Poyet et al. show that industrialization profoundly impacts the genome and function of gut bacteria, with implications for antibiotic resistance and other major health concerns. They also reveal that the functions of transferred genes reflect host lifestyle. In the cover image, Hadza foragers rest by the fire under starlight after a long hunt. The remaining hunter-gatherer populations worldwide currently maintain the richest microbiome diversity, but their lifestyles are under significant pressure to change. Lake Eyasi, Tanzania. February 2018. Artist/image source: Christopher Corzett (corzett@usc.edu) for the Global Microbiome Conservancy.

Leading Edge

Letters

  • Lack of evidence for a role of PIWIL1 variants in human male infertility

    • M.S. Oud,
    • L. Volozonoka,
    • C. Friedrich,
    • S. Kliesch,
    • L. Nagirnaja,
    • C. Gilissen,
    • M.K. O’Bryan,
    • R.I. McLachlan,
    • K.I. Aston,
    • F. Tüttelmann,
    • D.F. Conrad,
    • J.A. Veltman
    Infertility affects one in six couples, half of which is explained by a male factor (Tüttelmann et al., 2018). While thousands of genes are involved in spermatogenesis, there is a lack of diagnostically relevant genes. Critical evaluation of newly reported candidate genes is important before incorporating these into the diagnostic workup. As part of a recently performed clinical validity assessment (Oud et al., 2019), an effort by the International Male Infertility Genomics Consortium (IMIGC, http://imigc.org/ ), a closer look was taken at the quality of the evidence described in this journal by Gou et al.
  • Reply to Lack of evidence for a role of PIWIL1 variants in human male infertility

    • Lan-Tao Gou,
    • Yang Gao,
    • Jun-Yan Kang,
    • Xin Wang,
    • Hao Chen,
    • Min-Min Hua,
    • Zheng Li,
    • Dangsheng Li,
    • Xiang-Dong Fu,
    • Hui-Juan Shi,
    • Shuhua Xu,
    • Mo-Fang Liu
    A letter by Oud et al. (2021) raised an issue on the authenticity of the PIWIL1 D-box mutations we identified in 3 out of 413 Han Chinese patients with idiopathic azoospermia (Gou et al., 2017). By sequencing a cohort of infertile men from Europe, the United States, and Australia, these authors could not detect the identical mutations in PIWIL1 as we reported in the patients of Han Chinese ancestry (Oud et al., 2021). Because of the seemly unusual feature of the mutations (two consecutive mutations from a short T run), these authors further questioned our Sanger sequencing data and the mutational mechanism.

Benchmarks

Conversations

  • Connecting communities to tackle cancer from many sides

    Interdisciplinary work has played a key role in Dr. Elizabeth Eisenhauer’s wide-ranging research contributions and leadership in cancer clinical trials, drug delivery, treatment standards, and research and prevention strategy. Cell editor Emma Yee talked with Dr. Eisenhauer, recipient of the 2021 Canada Gairdner Wightman Award, to learn more about the factors that influenced her work in cancer care and the lessons she learned along the way. This conversation is presented below, edited for clarity and length.
  • Transforming lives through genetics

    Mary-Claire King’s approach to genetics has had a major impact on breast and ovarian cancer and, more recently, mental illnesses including schizophrenia. Science writer Kendall Morgan talked with Mary-Claire, recipient of a 2021 Canada Gairdner International Award, about her life, her lengthy quest to discover the genetic basis of susceptibility to breast cancer, the struggles for women in science, and much more. An edited version of this conversation is presented below.
  • One world, one health

    • Joseph Sriyal Malik Peiris
    The past year has underscored the threat that emerging viruses pose to global health. The 2021 John Dirks Canada Gairdner Global Health award recognizes the contributions of Joseph Sriyal Malik Peiris and Yi Guan toward understanding the origins and options for control of newly emerging infectious disease outbreaks in Asia, notably zoonotic influenza and severe acute respiratory syndrome (SARS). Nicole Neuman of Cell corresponded with Malik Peiris about his path to studying emerging infectious diseases and the challenges of this work.
  • The origins of viral infection sleuth

    The events of the past year have underscored the serious and rapid threat that emerging viruses pose to global health. However, much of the rapid progress in understanding and combating SARS-CoV-2 was made possible because of the decades of important groundwork laid from researchers studying other emergent infectious diseases. The 2021 John Dirks Canada Gairdner Global Health award recognizes the contributions of Joseph Sriyal Malik Peiris and Yi Guan toward understanding the origins and options for control of newly emerging infectious disease outbreaks in Asia, notably zoonotic influenza and severe acute respiratory syndrome (SARS).

Previews

  • Advancing the ethical dialogue about monkey/human chimeric embryos

    • Henry T. Greely,
    • Nita A. Farahany
    In this issue of Cell, Tan et al. report the first injection of human stem cells into in vitro non-human primate blastocysts with significant survival of the human cells, raising new scientific possibilities but also important ethical issues.
  • Is genetic ancestry a tool to combat health disparities?

    • Rex L. Chisholm
    The use of race and ethnicity in medicine has become a matter of intense debate. Currently the social construct of race and ethnicity is far from precise, serving as a poor proxy for ancestry. In this issue of Cell, Belbin et al. provide an interesting framework for better characterizing population substructure in a diverse urban environment.
  • Founder cells shape brain evolution

    • Jing Liu,
    • Debra L. Silver
    Humans have an extraordinarily expanded and complex cerebral cortex, relative to non-human primates. Yet the mechanisms underlying cortical differences across evolution are unclear. A new study by Benito-Kwiecinski et al. employs cerebral organoids derived across great apes to implicate neuroepithelial progenitor shape transitions in human cortical expansion.
  • Neu(ronal) custodians of cutaneous immunity

    • Kody Paul Mansfield,
    • Shruti Naik
    Sensory neurons have surfaced as key instigators of skin inflammation. In this issue of Cell, Zhang et al. define an anti-inflammatory Langerhans cell (LC)-neuron-mast cell (MC) circuit that underlies skin immune homeostasis. They uncover a role for LCs in maintaining innervation of MrgprD+ nonpeptidergic neurons that restrain MC activation via glutamate secretion.

Perspective

Review

  • The aging lung: Physiology, disease, and immunity

    • Jaime L. Schneider,
    • Jared H. Rowe,
    • Carolina Garcia-de-Alba,
    • Carla F. Kim,
    • Arlene H. Sharpe,
    • Marcia C. Haigis
    Recent cellular and molecular studies have given insight into why the incidence and/or severity of many lung diseases, from lung cancer to COVID-19, increase with age.

Articles

  • Chimeric contribution of human extended pluripotent stem cells to monkey embryos ex vivo

    • Tao Tan,
    • Jun Wu,
    • Chenyang Si,
    • Shaoxing Dai,
    • Youyue Zhang,
    • Nianqin Sun,
    • E Zhang,
    • Honglian Shao,
    • Wei Si,
    • Pengpeng Yang,
    • Hong Wang,
    • Zhenzhen Chen,
    • Ran Zhu,
    • Yu Kang,
    • Reyna Hernandez-Benitez,
    • Llanos Martinez Martinez,
    • Estrella Nuñez Delicado,
    • W. Travis Berggren,
    • May Schwarz,
    • Zongyong Ai,
    • Tianqing Li,
    • Hongkui Deng,
    • Concepcion Rodriguez Esteban,
    • Weizhi Ji,
    • Yuyu Niu,
    • Juan Carlos Izpisua Belmonte
    Human cells, in the form of extended pluripotent stem cells, have the ability to contribute to both embryonic and extra-embryonic lineages in ex-vivo-cultured monkey embryos.
  • Genetically engineered myeloid cells rebalance the core immune suppression program in metastasis

    • Sabina Kaczanowska,
    • Daniel W. Beury,
    • Vishaka Gopalan,
    • Arielle K. Tycko,
    • Haiying Qin,
    • Miranda E. Clements,
    • Justin Drake,
    • Chiadika Nwanze,
    • Meera Murgai,
    • Zachary Rae,
    • Wei Ju,
    • Katherine A. Alexander,
    • Jessica Kline,
    • Cristina F. Contreras,
    • Kristin M. Wessel,
    • Shil Patel,
    • Sridhar Hannenhalli,
    • Michael C. Kelly,
    • Rosandra N. Kaplan
    Genetically engineered myeloid cells expressing IL-12 can reverse the immunosuppressive environment developed during metastatic progression by augmenting T cell responses and reducing metastatic burden in preclinical models.
  • Elevated rates of horizontal gene transfer in the industrialized human microbiome

    • Mathieu Groussin,
    • Mathilde Poyet,
    • Ainara Sistiaga,
    • Sean M. Kearney,
    • Katya Moniz,
    • Mary Noel,
    • Jeff Hooker,
    • Sean M. Gibbons,
    • Laure Segurel,
    • Alain Froment,
    • Rihlat Said Mohamed,
    • Alain Fezeu,
    • Vanessa A. Juimo,
    • Sophie Lafosse,
    • Francis E. Tabe,
    • Catherine Girard,
    • Deborah Iqaluk,
    • Le Thanh Tu Nguyen,
    • B. Jesse Shapiro,
    • Jenni Lehtimäki,
    • Lasse Ruokolainen,
    • Pinja P. Kettunen,
    • Tommi Vatanen,
    • Shani Sigwazi,
    • Audax Mabulla,
    • Manuel Domínguez-Rodrigo,
    • Yvonne A. Nartey,
    • Adwoa Agyei-Nkansah,
    • Amoako Duah,
    • Yaw A. Awuku,
    • Kenneth A. Valles,
    • Shadrack O. Asibey,
    • Mary Y. Afihene,
    • Lewis R. Roberts,
    • Amelie Plymoth,
    • Charles A. Onyekwere,
    • Roger E. Summons,
    • Ramnik J. Xavier,
    • Eric J. Alm
    A worldwide microbiome analysis from 15 populations along the industrialization gradient reveals that horizontal gene transfer occurs on short timescales and that microbiomes continuously acquire new functionality based on host lifestyle.
  • Toward a fine-scale population health monitoring system

    • Gillian M. Belbin,
    • Sinead Cullina,
    • Stephane Wenric,
    • Emily R. Soper,
    • Benjamin S. Glicksberg,
    • Denis Torre,
    • Arden Moscati,
    • Genevieve L. Wojcik,
    • Ruhollah Shemirani,
    • Noam D. Beckmann,
    • Ariella Cohain,
    • Elena P. Sorokin,
    • Danny S. Park,
    • Jose-Luis Ambite,
    • Steve Ellis,
    • Adam Auton,
    • CBIPM Genomics Team,
    • Regeneron Genetics Center,
    • Erwin P. Bottinger,
    • Judy H. Cho,
    • Ruth J.F. Loos,
    • Noura S. Abul-Husn,
    • Noah A. Zaitlen,
    • Christopher R. Gignoux,
    • Eimear E. Kenny
    Taking a quantitative approach to genetic ancestry in health systems furthers understanding of disease burdens specific to fine-scale populations and the environmental and demographic ties that can impact disease.
  • An early cell shape transition drives evolutionary expansion of the human forebrain

    • Silvia Benito-Kwiecinski,
    • Stefano L. Giandomenico,
    • Magdalena Sutcliffe,
    • Erlend S. Riis,
    • Paula Freire-Pritchett,
    • Iva Kelava,
    • Stephanie Wunderlich,
    • Ulrich Martin,
    • Gregory A. Wray,
    • Kate McDole,
    • Madeline A. Lancaster
    Cerebral organoid models reveal that differences in the duration of a developmental transitional state driven by the factor ZEB2 underlie the basis of brain expansion in humans in comparison to great apes.
  • Simultaneous binding of Guidance Cues NET1 and RGM blocks extracellular NEO1 signaling

    • Ross A. Robinson,
    • Samuel C. Griffiths,
    • Lieke L. van de Haar,
    • Tomas Malinauskas,
    • Eljo Y. van Battum,
    • Pavol Zelina,
    • Rebekka A. Schwab,
    • Dimple Karia,
    • Lina Malinauskaite,
    • Sara Brignani,
    • Marleen H. van den Munkhof,
    • Özge Düdükcü,
    • Anna A. De Ruiter,
    • Dianne M.A. Van den Heuvel,
    • Benjamin Bishop,
    • Jonathan Elegheert,
    • A. Radu Aricescu,
    • R. Jeroen Pasterkamp,
    • Christian Siebold
    When extracellular guidance molecules Netrin and RGM that have opposing functions simultaneously bind the Neogenin receptor, a super-complex is formed that diminishes their functional outputs.
  • Structure and gating mechanism of the α7 nicotinic acetylcholine receptor

    • Colleen M. Noviello,
    • Anant Gharpure,
    • Nuriya Mukhtasimova,
    • Rico Cabuco,
    • Leah Baxter,
    • Dominika Borek,
    • Steven M. Sine,
    • Ryan E. Hibbs
    Cryo-EM structures of the α7 nicotinic acetylcholine receptor in three major conformational states of the gating cycle—resting, activated, and desensitized—along with functional studies reveal components involved in calcium conductance and allosteric coupling of ligand binding to channel opening.
  • The molecular basis for sarcomere organization in vertebrate skeletal muscle

    • Zhexin Wang,
    • Michael Grange,
    • Thorsten Wagner,
    • Ay Lin Kho,
    • Mathias Gautel,
    • Stefan Raunser
    Visualizing the mouse sarcomere in the rigor state using electron cryo-tomography reveals architectural details of the different zones and provides insight into how key factors are arranged within them to support function during muscle contraction.
  • Nonpeptidergic neurons suppress mast cells via glutamate to maintain skin homeostasis

    • Shiqun Zhang,
    • Tara N. Edwards,
    • Virendra K. Chaudhri,
    • Jianing Wu,
    • Jonathan A. Cohen,
    • Toshiro Hirai,
    • Natalie Rittenhouse,
    • Elizabeth G. Schmitz,
    • Paul Yifan Zhou,
    • Benjamin D. McNeil,
    • Yi Yang,
    • H. Richard Koerber,
    • Tina L. Sumpter,
    • Amanda C. Poholek,
    • Brian M. Davis,
    • Kathryn M. Albers,
    • Harinder Singh,
    • Daniel H. Kaplan
    A subset of sensory neurons marked by MrgprD maintain skin homeostasis by suppressing mast cell inflammatory responses.
  • BET inhibition blocks inflammation-induced cardiac dysfunction and SARS-CoV-2 infection

    • Richard J. Mills,
    • Sean J. Humphrey,
    • Patrick R.J. Fortuna,
    • Mary Lor,
    • Simon R. Foster,
    • Gregory A. Quaife-Ryan,
    • Rebecca L. Johnston,
    • Troy Dumenil,
    • Cameron Bishop,
    • Rajeev Rudraraju,
    • Daniel J. Rawle,
    • Thuy Le,
    • Wei Zhao,
    • Leo Lee,
    • Charley Mackenzie-Kludas,
    • Neda R. Mehdiabadi,
    • Christopher Halliday,
    • Dean Gilham,
    • Li Fu,
    • Stephen J. Nicholls,
    • Jan Johansson,
    • Michael Sweeney,
    • Norman C.W. Wong,
    • Ewelina Kulikowski,
    • Kamil A. Sokolowski,
    • Brian W.C. Tse,
    • Lynn Devilée,
    • Holly K. Voges,
    • Liam T. Reynolds,
    • Sophie Krumeich,
    • Ellen Mathieson,
    • Dad Abu-Bonsrah,
    • Kathy Karavendzas,
    • Brendan Griffen,
    • Drew Titmarsh,
    • David A. Elliott,
    • James McMahon,
    • Andreas Suhrbier,
    • Kanta Subbarao,
    • Enzo R. Porrello,
    • Mark J. Smyth,
    • Christian R. Engwerda,
    • Kelli P.A. MacDonald,
    • Tobias Bald,
    • David E. James,
    • James E. Hudson
    COVID-19 causes cardiac injury, although mechanisms and effective therapeutics are lacking. In this study, Mills et al., show that cytokines elevated in COVID-19 patients drive cardiac dysfunction. These responses are mapped using phosphoproteomics and single nuclei RNA sequencing, enabling a targeted drug screen to identify therapeutics for rapid repurposing. BET inhibitors were identified as leading candidates to block cardiac dysfunction and decrease SARS-CoV-2 cardiac infection.
  • The antigenic anatomy of SARS-CoV-2 receptor binding domain

    • Wanwisa Dejnirattisai,
    • Daming Zhou,
    • Helen M. Ginn,
    • Helen M.E. Duyvesteyn,
    • Piyada Supasa,
    • James Brett Case,
    • Yuguang Zhao,
    • Thomas S. Walter,
    • Alexander J. Mentzer,
    • Chang Liu,
    • Beibei Wang,
    • Guido C. Paesen,
    • Jose Slon-Campos,
    • César López-Camacho,
    • Natasha M. Kafai,
    • Adam L. Bailey,
    • Rita E. Chen,
    • Baoling Ying,
    • Craig Thompson,
    • Jai Bolton,
    • Alex Fyfe,
    • Sunetra Gupta,
    • Tiong Kit Tan,
    • Javier Gilbert-Jaramillo,
    • William James,
    • Michael Knight,
    • Miles W. Carroll,
    • Donal Skelly,
    • Christina Dold,
    • Yanchun Peng,
    • Robert Levin,
    • Tao Dong,
    • Andrew J. Pollard,
    • Julian C. Knight,
    • Paul Klenerman,
    • Nigel Temperton,
    • David R. Hall,
    • Mark A. Williams,
    • Neil G. Paterson,
    • Felicity K.R. Bertram,
    • C. Alistair Siebert,
    • Daniel K. Clare,
    • Andrew Howe,
    • Julika Radecke,
    • Yun Song,
    • Alain R. Townsend,
    • Kuan-Ying A. Huang,
    • Elizabeth E. Fry,
    • Juthathip Mongkolsapaya,
    • Michael S. Diamond,
    • Jingshan Ren,
    • David I. Stuart,
    • Gavin R. Screaton
    Dejnirattisai et al. present an in-depth study of the human antibody response to SARS-CoV-2 infection. By characterizing 377 human mAbs from recovered COVID-19 patients, and determining 19 protein structures, they construct a map of antibody footprints on the RBD that describes in great detail its antigenic anatomy.
  • Reduced neutralization of SARS-CoV-2 B.1.1.7 variant by convalescent and vaccine sera

    • Piyada Supasa,
    • Daming Zhou,
    • Wanwisa Dejnirattisai,
    • Chang Liu,
    • Alexander J. Mentzer,
    • Helen M. Ginn,
    • Yuguang Zhao,
    • Helen M.E. Duyvesteyn,
    • Rungtiwa Nutalai,
    • Aekkachai Tuekprakhon,
    • Beibei Wang,
    • Guido C. Paesen,
    • Jose Slon-Campos,
    • César López-Camacho,
    • Bassam Hallis,
    • Naomi Coombes,
    • Kevin R. Bewley,
    • Sue Charlton,
    • Thomas S. Walter,
    • Eleanor Barnes,
    • Susanna J. Dunachie,
    • Donal Skelly,
    • Sheila F. Lumley,
    • Natalie Baker,
    • Imam Shaik,
    • Holly E. Humphries,
    • Kerry Godwin,
    • Nick Gent,
    • Alex Sienkiewicz,
    • Christina Dold,
    • Robert Levin,
    • Tao Dong,
    • Andrew J. Pollard,
    • Julian C. Knight,
    • Paul Klenerman,
    • Derrick Crook,
    • Teresa Lambe,
    • Elizabeth Clutterbuck,
    • Sagida Bibi,
    • Amy Flaxman,
    • Mustapha Bittaye,
    • Sandra Belij-Rammerstorfer,
    • Sarah Gilbert,
    • David R. Hall,
    • Mark A. Williams,
    • Neil G. Paterson,
    • William James,
    • Miles W. Carroll,
    • Elizabeth E. Fry,
    • Juthathip Mongkolsapaya,
    • Jingshan Ren,
    • David I. Stuart,
    • Gavin R. Screaton
    The SARS-CoV-2 B.1.1.7 variant is not neutralized as easily as the original form of the virus. Some public antibodies cannot neutralize B.1.1.7, due to altered light-chain contacts with residue 501. However, B.1.1.7 does not show widespread escape from monoclonal antibodies, natural antibody responses, or vaccines.
  • Soluble ACE2-mediated cell entry of SARS-CoV-2 via interaction with proteins related to the renin-angiotensin system

    • Man Lung Yeung,
    • Jade Lee Lee Teng,
    • Lilong Jia,
    • Chaoyu Zhang,
    • Chengxi Huang,
    • Jian-Piao Cai,
    • Runhong Zhou,
    • Kwok-Hung Chan,
    • Hanjun Zhao,
    • Lin Zhu,
    • Kam-Leung Siu,
    • Sin-Yee Fung,
    • Susan Yung,
    • Tak Mao Chan,
    • Kelvin Kai-Wang To,
    • Jasper Fuk-Woo Chan,
    • Zongwei Cai,
    • Susanna Kar Pui Lau,
    • Zhiwei Chen,
    • Dong-Yan Jin,
    • Patrick Chiu Yat Woo,
    • Kwok-Yung Yuen
    Using an infection-permissive human kidney cell line, Yeung et al. show that a soluble form of ACE2 that is cleaved and liberated from the host cell surface mediates SARS-CoV-2 binding and uptake by receptors involved in renin-angiotensin system signaling.

Resources

  • A trans-complementation system for SARS-CoV-2 recapitulates authentic viral replication without virulence

    • Xianwen Zhang,
    • Yang Liu,
    • Jianying Liu,
    • Adam L. Bailey,
    • Kenneth S. Plante,
    • Jessica A. Plante,
    • Jing Zou,
    • Hongjie Xia,
    • Nathen E. Bopp,
    • Patricia V. Aguilar,
    • Ping Ren,
    • Vineet D. Menachery,
    • Michael S. Diamond,
    • Scott C. Weaver,
    • Xuping Xie,
    • Pei-Yong Shi
    Zhang et al. develop a trans-complementation system to produce single-round infectious SARS-CoV-2 that recapitulates authentic viral infection and replication. They then show the system can be safely used at biosafety level 2 for high-throughput antiviral testing.
  • Characterizing genetic intra-tumor heterogeneity across 2,658 human cancer genomes

    • Stefan C. Dentro,
    • Ignaty Leshchiner,
    • Kerstin Haase,
    • Maxime Tarabichi,
    • Jeff Wintersinger,
    • Amit G. Deshwar,
    • Kaixian Yu,
    • Yulia Rubanova,
    • Geoff Macintyre,
    • Jonas Demeulemeester,
    • Ignacio Vázquez-García,
    • Kortine Kleinheinz,
    • Dimitri G. Livitz,
    • Salem Malikic,
    • Nilgun Donmez,
    • Subhajit Sengupta,
    • Pavana Anur,
    • Clemency Jolly,
    • Marek Cmero,
    • Daniel Rosebrock,
    • Steven E. Schumacher,
    • Yu Fan,
    • Matthew Fittall,
    • Ruben M. Drews,
    • Xiaotong Yao,
    • Thomas B.K. Watkins,
    • Juhee Lee,
    • Matthias Schlesner,
    • Hongtu Zhu,
    • David J. Adams,
    • Nicholas McGranahan,
    • Charles Swanton,
    • Gad Getz,
    • Paul C. Boutros,
    • Marcin Imielinski,
    • Rameen Beroukhim,
    • S. Cenk Sahinalp,
    • Yuan Ji,
    • Martin Peifer,
    • Inigo Martincorena,
    • Florian Markowetz,
    • Ville Mustonen,
    • Ke Yuan,
    • Moritz Gerstung,
    • Paul T. Spellman,
    • Wenyi Wang,
    • Quaid D. Morris,
    • David C. Wedge,
    • Peter Van Loo
    • on behalf of the PCAWG Evolution and Heterogeneity Working Group and the PCAWG Consortium
    Dentro et al. provide a comprehensive annotation of intra-tumor heterogeneity and its drivers in cancer evolution.

Editorial note

Corrections

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