Volume 24 Issue 10, October 2018

Volume 24 Issue 10

Defining healthy microbiomes

Clinical studies have demonstrated that the composition of the gut microbiome often links to patient health. However, recent work has also revealed extensive variation in the composition of the gut microbiome, even among seemingly healthy patients. In this issue of Nature Medicine, two large-scale clinical microbiome studies provide transformative insight into two factors contributing to this variation: ethnicity and geography. The cover art is a conceptual representation of the work by Hong-wei Zhou and colleagues identifying host location as having the strongest association with microbiota variation in a cohort of 7,009 individuals from 14 districts within a single province in China.

See Zhou and colleagues, Deschasaux et al. and News & Views by Sharpton and Gaulke

Image credit: Tianxing Shi. Cover design: Erin Dewalt

Editorial

  • Editorial |

    Thanks to improvements in data collection and analysis, some polygenic risk scores that predict disease risk are approaching the same predictive accuracy offered by tests for monogenic mutations. The time to think about how best to incorporate polygenic tests in the clinic is now.

News Feature

  • News Feature |

    Virologists say sewage systems are flush with opportunity.

    • Colin Barras
  • News Feature |

    Will the rise of patient navigators help avert health disparities?

    • Shraddha Chakradhar

Research Highlights

News & Views

  • News & Views |

    Acquired resistance to CD19-targeted CAR T cell therapy can occur through mutations in the CD19 gene or after insertion of a chimeric antigen receptor (CAR) into leukemia cells, resulting in the adjacent receptor being masked by the CAR.

    • Sarwish Rafiq
    •  & Renier J. Brentjens
  • News & Views |

    Informing physicians who prescribe opioids about opioid-linked deaths in their practice reduces future opioid prescribing.

    • Nora D. Volkow
    •  & Ruben Baler

Brief Communications

  • Brief Communication |

    A CAR gene unintentionally introduced in a contaminating leukemia cell during the manufacturing of CAR T cells caused a patient to relapse after therapy.

    • Marco Ruella
    • , Jun Xu
    • , David M. Barrett
    • , Joseph A. Fraietta
    • , Tyler J. Reich
    • , David E. Ambrose
    • , Michael Klichinsky
    • , Olga Shestova
    • , Prachi R. Patel
    • , Irina Kulikovskaya
    • , Farzana Nazimuddin
    • , Vijay G. Bhoj
    • , Elena J. Orlando
    • , Terry J. Fry
    • , Hans Bitter
    • , Shannon L. Maude
    • , Bruce L. Levine
    • , Christopher L. Nobles
    • , Frederic D. Bushman
    • , Regina M. Young
    • , John Scholler
    • , Saar I. Gill
    • , Carl H. June
    • , Stephan A. Grupp
    • , Simon F. Lacey
    •  & J. Joseph Melenhorst
  • Brief Communication |

    Mutations in the CD19 gene suggesting irreversible loss of its surface expression are identified in the majority of analyzed cases of CD19 relapse in two clinical trials of pediatric ALL CD19 CAR T therapy, offering considerations for the rational choice of follow-up therapies.

    • Elena J. Orlando
    • , Xia Han
    • , Catherine Tribouley
    • , Patricia A. Wood
    • , Rebecca J. Leary
    • , Markus Riester
    • , John E. Levine
    • , Muna Qayed
    • , Stephan A. Grupp
    • , Michael Boyer
    • , Barbara De Moerloose
    • , Eneida R. Nemecek
    • , Henrique Bittencourt
    • , Hidefumi Hiramatsu
    • , Jochen Buechner
    • , Stella M. Davies
    • , Michael R. Verneris
    • , Kevin Nguyen
    • , Jennifer L. Brogdon
    • , Hans Bitter
    • , Michael Morrissey
    • , Piotr Pierog
    • , Serafino Pantano
    • , Jeffrey A. Engelman
    •  & Wendy Winckler

Letters

  • Letter |

    The long-term follow-up results of a phase 1/2 retinal gene therapy clinical trial for choroideremia ( NCT01461213 ) support the safety and efficacy of the treatment.

    • Kanmin Xue
    • , Jasleen K Jolly
    • , Alun R. Barnard
    • , Anna Rudenko
    • , Anna P. Salvetti
    • , Maria I. Patrício
    • , Thomas L. Edwards
    • , Markus Groppe
    • , Harry O. Orlans
    • , Tanya Tolmachova
    • , Graeme C. Black
    • , Andrew R. Webster
    • , Andrew J. Lotery
    • , Graham E. Holder
    • , Susan M. Downes
    • , Miguel C. Seabra
    •  & Robert E. MacLaren

    Nature Outlook:

  • Letter |

    Viral-mediated base editing in utero enables therapeutic editing of two metabolic genes in mice.

    • Avery C. Rossidis
    • , John D. Stratigis
    • , Alexandra C. Chadwick
    • , Heather A. Hartman
    • , Nicholas J. Ahn
    • , Haiying Li
    • , Kshitiz Singh
    • , Barbara E. Coons
    • , Li Li
    • , Wenjian Lv
    • , Philip W. Zoltick
    • , Deepthi Alapati
    • , William Zacharias
    • , Rajan Jain
    • , Edward E. Morrisey
    • , Kiran Musunuru
    •  & William H. Peranteau

    Collection:

  • Letter |

    AAV-mediated base editing corrects an autosomal recessive mutation in the Pahenu2 gene and ameliorates molecular deficits in a mouse model of metabolic liver disease.

    • Lukas Villiger
    • , Hiu Man Grisch-Chan
    • , Helen Lindsay
    • , Femke Ringnalda
    • , Chiara B. Pogliano
    • , Gabriella Allegri
    • , Ralph Fingerhut
    • , Johannes Häberle
    • , Joao Matos
    • , Mark D. Robinson
    • , Beat Thöny
    •  & Gerald Schwank

    Collection:

  • Letter |

    Stool microbiota composition correlates with the ethnic backgrounds of people living in the same city, suggesting that geographical location and ethnicity have distinct effects on microbiota.

    • Mélanie Deschasaux
    • , Kristien E. Bouter
    • , Andrei Prodan
    • , Evgeni Levin
    • , Albert K. Groen
    • , Hilde Herrema
    • , Valentina Tremaroli
    • , Guido J. Bakker
    • , Ilias Attaye
    • , Sara-Joan Pinto-Sietsma
    • , Daniel H. van Raalte
    • , Marieke B. Snijder
    • , Mary Nicolaou
    • , Ron Peters
    • , Aeilko H. Zwinderman
    • , Fredrik Bäckhed
    •  & Max Nieuwdorp

    Collection:

  • Letter |

    The definition of a 'healthy' microbiome is impacted by geographic regional variations.

    • Yan He
    • , Wei Wu
    • , Hui-Min Zheng
    • , Pan Li
    • , Daniel McDonald
    • , Hua-Fang Sheng
    • , Mu-Xuan Chen
    • , Zi-Hui Chen
    • , Gui-Yuan Ji
    • , Zhong-Dai-Xi Zheng
    • , Prabhakar Mujagond
    • , Xiao-Jiao Chen
    • , Zu-Hua Rong
    • , Peng Chen
    • , Li-Yi Lyu
    • , Xian Wang
    • , Chong-Bin Wu
    • , Nan Yu
    • , Yan-Jun Xu
    • , Jia Yin
    • , Jeroen Raes
    • , Rob Knight
    • , Wen-Jun Ma
    •  & Hong-Wei Zhou

    Collection:

  • Letter |

    Large tumors induce anemia and expansion of CD45+ immature erythroid cells, which represent a major immunosuppressive population in the spleen, contributing to systemic suppression of T cell immunity in late-stage cancer.

    • Lintao Zhao
    • , Ran He
    • , Haixia Long
    • , Bo Guo
    • , Qingzhu Jia
    • , Diyuan Qin
    • , Si-Qi Liu
    • , Zhongyu Wang
    • , Tong Xiang
    • , Jue Zhang
    • , Yulong Tan
    • , Jiani Huang
    • , Junying Chen
    • , Fang Wang
    • , Minglu Xiao
    • , Jianbao Gao
    • , Xinxin Yang
    • , Hao Zeng
    • , Xinxin Wang
    • , Chunyan Hu
    • , Peter B. Alexander
    • , Alistair L. J. Symonds
    • , Jia Yu
    • , Yisong Wan
    • , Qi-Jing Li
    • , Lilin Ye
    •  & Bo Zhu
  • Letter |

    A gene signature identified in spontaneously regressing neuroblastoma identifies responders to immune checkpoint blockade among patients with melanoma with accuracy superior to previously reported biomarkers.

    • Noam Auslander
    • , Gao Zhang
    • , Joo Sang Lee
    • , Dennie T. Frederick
    • , Benchun Miao
    • , Tabea Moll
    • , Tian Tian
    • , Zhi Wei
    • , Sanna Madan
    • , Ryan J. Sullivan
    • , Genevieve Boland
    • , Keith Flaherty
    • , Meenhard Herlyn
    •  & Eytan Ruppin

Articles

  • Article |

    An algorithm-selected gene signature focused on tumor immune evasion and suppression predicts response to immune checkpoint blockade in melanoma, exceeding the accuracy of current clinical biomarkers.

    • Peng Jiang
    • , Shengqing Gu
    • , Deng Pan
    • , Jingxin Fu
    • , Avinash Sahu
    • , Xihao Hu
    • , Ziyi Li
    • , Nicole Traugh
    • , Xia Bu
    • , Bo Li
    • , Jun Liu
    • , Gordon J. Freeman
    • , Myles A. Brown
    • , Kai W. Wucherpfennig
    •  & X. Shirley Liu
  • Article |

    A convolutional neural network model using feature extraction and machine-learning techniques provides a tool for classification of lung cancer histopathology images and predicting mutational status of driver oncogenes

    • Nicolas Coudray
    • , Paolo Santiago Ocampo
    • , Theodore Sakellaropoulos
    • , Navneet Narula
    • , Matija Snuderl
    • , David Fenyö
    • , Andre L. Moreira
    • , Narges Razavian
    •  & Aristotelis Tsirigos
  • Article |

    CRISPR–Cas9-mediated gene editing of TSC1 and TSC2 in human pluripotent stem cells is used to investigate the contribution of tuberous sclerosis complex–mechanistic target of rapamycin complex 1 signaling to human neural development in two-dimensional monolayer and three-dimensional spheroid models of the neurodevelopmental disorder tuberous sclerosis complex.

    • John D. Blair
    • , Dirk Hockemeyer
    •  & Helen S. Bateup
  • Article |

    iPSC-derived motor neurons from over 30 heterogeneous sporadic ALS cases exhibit pathologies correlated with clinical disease progression, are more similar to FUS/TDP-43 familial ALS than SOD1-ALS and are corrected by repurposing of ropinirole.

    • Koki Fujimori
    • , Mitsuru Ishikawa
    • , Asako Otomo
    • , Naoki Atsuta
    • , Ryoichi Nakamura
    • , Tetsuya Akiyama
    • , Shinji Hadano
    • , Masashi Aoki
    • , Hideyuki Saya
    • , Gen Sobue
    •  & Hideyuki Okano
  • Article |

    Distinct routes of immunization elicit different antibody isotypes and functions associated with protection against SIV infection that converge on phagocytosis as a candidate protective mechanism of independent SIV vaccines.

    • Margaret E. Ackerman
    • , Jishnu Das
    • , Srivamshi Pittala
    • , Thomas Broge
    • , Caitlyn Linde
    • , Todd J. Suscovich
    • , Eric P. Brown
    • , Todd Bradley
    • , Harini Natarajan
    • , Shu Lin
    • , Jessica K. Sassic
    • , Sean O’Keefe
    • , Nickita Mehta
    • , Derrick Goodman
    • , Magdalena Sips
    • , Joshua A. Weiner
    • , Georgia D. Tomaras
    • , Barton F. Haynes
    • , Douglas A. Lauffenburger
    • , Chris Bailey-Kellogg
    • , Mario Roederer
    •  & Galit Alter
  • Article |

    Interdependence between YAP/TAZ and BRD4 drives transcriptional addiction in cancer cells and determines sensitivity to BET inhibition.

    • Francesca Zanconato
    • , Giusy Battilana
    • , Mattia Forcato
    • , Letizia Filippi
    • , Luca Azzolin
    • , Andrea Manfrin
    • , Erika Quaranta
    • , Daniele Di Biagio
    • , Gianluca Sigismondo
    • , Vincenza Guzzardo
    • , Pascale Lejeune
    • , Bernard Haendler
    • , Jeroen Krijgsveld
    • , Matteo Fassan
    • , Silvio Bicciato
    • , Michelangelo Cordenonsi
    •  & Stefano Piccolo

Resources

  • Resource |

    In-depth methylation analysis of formalin-fixed paraffin-embedded glioblastoma samples demonstrates heterogeneity between primary and recurring tumors and enables prediction of composition of the tumor microenvironment and insights into progression.

    • Johanna Klughammer
    • , Barbara Kiesel
    • , Thomas Roetzer
    • , Nikolaus Fortelny
    • , Amelie Nemc
    • , Karl-Heinz Nenning
    • , Julia Furtner
    • , Nathan C. Sheffield
    • , Paul Datlinger
    • , Nadine Peter
    • , Martha Nowosielski
    • , Marco Augustin
    • , Mario Mischkulnig
    • , Thomas Ströbel
    • , Donat Alpar
    • , Bekir Ergüner
    • , Martin Senekowitsch
    • , Patrizia Moser
    • , Christian F. Freyschlag
    • , Johannes Kerschbaumer
    • , Claudius Thomé
    • , Astrid E. Grams
    • , Günther Stockhammer
    • , Melitta Kitzwoegerer
    • , Stefan Oberndorfer
    • , Franz Marhold
    • , Serge Weis
    • , Johannes Trenkler
    • , Johanna Buchroithner
    • , Josef Pichler
    • , Johannes Haybaeck
    • , Stefanie Krassnig
    • , Kariem Mahdy Ali
    • , Gord von Campe
    • , Franz Payer
    • , Camillo Sherif
    • , Julius Preiser
    • , Thomas Hauser
    • , Peter A. Winkler
    • , Waltraud Kleindienst
    • , Franz Würtz
    • , Tanisa Brandner-Kokalj
    • , Martin Stultschnig
    • , Stefan Schweiger
    • , Karin Dieckmann
    • , Matthias Preusser
    • , Georg Langs
    • , Bernhard Baumann
    • , Engelbert Knosp
    • , Georg Widhalm
    • , Christine Marosi
    • , Johannes A. Hainfellner
    • , Adelheid Woehrer
    •  & Christoph Bock

Amendments & Corrections