Browse Articles

  • Letter |

    Aptamer-based proteomic analysis of plasma from healthy individuals aged 18–95 years reveals wave-like patterns of protein expression that are associated with age-related diseases and phenotypic traits.

    • Benoit Lehallier
    • , David Gate
    • , Nicholas Schaum
    • , Tibor Nanasi
    • , Song Eun Lee
    • , Hanadie Yousef
    • , Patricia Moran Losada
    • , Daniela Berdnik
    • , Andreas Keller
    • , Joe Verghese
    • , Sanish Sathyan
    • , Claudio Franceschi
    • , Sofiya Milman
    • , Nir Barzilai
    •  & Tony Wyss-Coray
  • Editorial |

    The recent report of an antisense oligonucleotide therapy designed for only one patient spotlights regulatory, economic and ethical issues that must be grappled with in an era of accelerated development of ‘ultra-personalized’ drugs.

  • Turning Points |

    Rachel Ramoni is chief research and development officer for the Department of Veterans Affairs, where she oversees 2,000 active projects at more than 100 sites.

    • Rachel Ramoni
  • News Feature |

    To celebrate the end of our 25th anniversary year, we asked thought leaders and experts in the field to answer one question: What will shape the next 25 years of medical research?

  • Article |

    Herpes simplex virus-1 encephalitis is linked to variants in a small nucleolar RNA, suggesting a new mechanism for antiviral immunity in cortical neurons.

    • Fabien G. Lafaille
    • , Oliver Harschnitz
    • , Yoon Seung Lee
    • , Peng Zhang
    • , Mary L. Hasek
    • , Gaspard Kerner
    • , Yuval Itan
    • , Osefame Ewaleifoh
    • , Franck Rapaport
    • , Thomas M. Carlile
    • , Madalina E. Carter-Timofte
    • , Dominik Paquet
    • , Kerry Dobbs
    • , Bastian Zimmer
    • , Daxing Gao
    • , Maria F. Rojas-Duran
    • , Dylan Kwart
    • , Vimel Rattina
    • , Michael J. Ciancanelli
    • , Jessica L. McAlpine
    • , Lazaro Lorenzo
    • , Soraya Boucherit
    • , Flore Rozenberg
    • , Rabih Halwani
    • , Benoit Henry
    • , Naima Amenzoui
    • , Zobaida Alsum
    • , Laura Marques
    • , Joseph A. Church
    • , Saleh Al-Muhsen
    • , Marc Tardieu
    • , Ahmed Aziz Bousfiha
    • , Søren R. Paludan
    • , Trine Hyrup Mogensen
    • , Lluis Quintana-Murci
    • , Marc Tessier-Lavigne
    • , Gregory A. Smith
    • , Luigi D. Notarangelo
    • , Lorenz Studer
    • , Wendy Gilbert
    • , Laurent Abel
    • , Jean-Laurent Casanova
    •  & Shen-Ying Zhang
  • Turning Points |

    Julie Makani is an associate professor in the Department of Haematology and Blood Transfusion at Muhimbili University of Health and Allied Sciences in Dar es Salaam, where she helped Tanzania establish one of the world’s largest single-center study cohorts for sickle cell disease. She received the 2011 Royal Society Africa Award on the translation of genomics to health benefits.

    • Julie Makani
  • Perspective |

    Systemic chronic inflammation increases with age and is linked to the development of several diseases, as presented in this Perspective.

    • David Furman
    • , Judith Campisi
    • , Eric Verdin
    • , Pedro Carrera-Bastos
    • , Sasha Targ
    • , Claudio Franceschi
    • , Luigi Ferrucci
    • , Derek W. Gilroy
    • , Alessio Fasano
    • , Gary W. Miller
    • , Andrew H. Miller
    • , Alberto Mantovani
    • , Cornelia M. Weyand
    • , Nir Barzilai
    • , Jorg J. Goronzy
    • , Thomas A. Rando
    • , Rita B. Effros
    • , Alejandro Lucia
    • , Nicole Kleinstreuer
    •  & George M. Slavich
  • Article |

    Prenatal androgen exposure causes transgenerational increases in offspring susceptibility to polycystic ovary syndrome in adulthood.

    • Sanjiv Risal
    • , Yu Pei
    • , Haojiang Lu
    • , Maria Manti
    • , Romina Fornes
    • , Han-Pin Pui
    • , Zhiyi Zhao
    • , Julie Massart
    • , Claes Ohlsson
    • , Eva Lindgren
    • , Nicolas Crisosto
    • , Manuel Maliqueo
    • , Barbara Echiburú
    • , Amanda Ladrón de Guevara
    • , Teresa Sir-Petermann
    • , Henrik Larsson
    • , Mina A. Rosenqvist
    • , Carolyn E. Cesta
    • , Anna Benrick
    • , Qiaolin Deng
    •  & Elisabet Stener-Victorin
  • Article
    | Open Access

    Analysis of fully clinically annotated and sequenced melanoma tumor samples collected before anti-PD1 treatment suggests that determinants of response differ on the basis of previous anti-CTLA4 therapy, and that tumor mutational burden may not be a strong predictor of response across melanoma subtypes.

    • David Liu
    • , Bastian Schilling
    • , Derek Liu
    • , Antje Sucker
    • , Elisabeth Livingstone
    • , Livnat Jerby-Amon
    • , Lisa Zimmer
    • , Ralf Gutzmer
    • , Imke Satzger
    • , Carmen Loquai
    • , Stephan Grabbe
    • , Natalie Vokes
    • , Claire A. Margolis
    • , Jake Conway
    • , Meng Xiao He
    • , Haitham Elmarakeby
    • , Felix Dietlein
    • , Diana Miao
    • , Adam Tracy
    • , Helen Gogas
    • , Simone M. Goldinger
    • , Jochen Utikal
    • , Christian U. Blank
    • , Ricarda Rauschenberg
    • , Dagmar von Bubnoff
    • , Angela Krackhardt
    • , Benjamin Weide
    • , Sebastian Haferkamp
    • , Felix Kiecker
    • , Ben Izar
    • , Levi Garraway
    • , Aviv Regev
    • , Keith Flaherty
    • , Annette Paschen
    • , Eliezer M. Van Allen
    •  & Dirk Schadendorf
  • News & Views |

    There is a transgenerational increase in the susceptibility of female offspring to developing PCOS that occurs via the female germline and is linked to fetal exposure to excess androgen.

    • H. M. Picton
    •  & A. H. Balen
  • Article |

    Imaging of muscle fibrosis with a handheld device could potentially serve as a biomarker for disease progression and response to therapy in patients with Duchenne muscular dystrophy.

    • Adrian P. Regensburger
    • , Lina M. Fonteyne
    • , Jörg Jüngert
    • , Alexandra L. Wagner
    • , Teresa Gerhalter
    • , Armin M. Nagel
    • , Rafael Heiss
    • , Florian Flenkenthaler
    • , Matthias Qurashi
    • , Markus F. Neurath
    • , Nikolai Klymiuk
    • , Elisabeth Kemter
    • , Thomas Fröhlich
    • , Michael Uder
    • , Joachim Woelfle
    • , Wolfgang Rascher
    • , Regina Trollmann
    • , Eckhard Wolf
    • , Maximilian J. Waldner
    •  & Ferdinand Knieling
  • News & Views |

    Enteroviral infection persistence as determined by host genetic susceptibility, rather than independent, short-lived infections, may contribute to islet autoimmunity and be a precursor to the development of type 1 diabetes.

    • Bart O. Roep
  • Letter |

    Analysis of known viruses in stool samples from young children with high genetic risk for type 1 diabetes shows that sustained enterovirus B (EV-B) infections, rather than independent, short-duration EV-B infections, might be involved in the development of islet autoimmunity, but not type 1 diabetes.

    • Kendra Vehik
    • , Kristian F. Lynch
    • , Matthew C. Wong
    • , Xiangjun Tian
    • , Matthew C. Ross
    • , Richard A. Gibbs
    • , Nadim J. Ajami
    • , Joseph F. Petrosino
    • , Marian Rewers
    • , Jorma Toppari
    • , Anette G. Ziegler
    • , Jin-Xiong She
    • , Ake Lernmark
    • , Beena Akolkar
    • , William A. Hagopian
    • , Desmond A. Schatz
    • , Jeffrey P. Krischer
    • , Heikki Hyöty
    •  & Richard E. Lloyd
  • Letter |

    Large-scale aptamer-based scanning of plasma proteins coupled with machine learning demonstrates proof-of-concept and feasibility of an individualized health check using a single blood sample.

    • Stephen A. Williams
    • , Mika Kivimaki
    • , Claudia Langenberg
    • , Aroon D. Hingorani
    • , J. P. Casas
    • , Claude Bouchard
    • , Christian Jonasson
    • , Mark A. Sarzynski
    • , Martin J. Shipley
    • , Leigh Alexander
    • , Jessica Ash
    • , Tim Bauer
    • , Jessica Chadwick
    • , Gargi Datta
    • , Robert Kirk DeLisle
    • , Yolanda Hagar
    • , Michael Hinterberg
    • , Rachel Ostroff
    • , Sophie Weiss
    • , Peter Ganz
    •  & Nicholas J. Wareham
  • Article |

    A combination of high-resolution imaging and modeling approaches facilitates the study of the mechanisms and clinical progression of non-alcoholic fatty liver disease in humans.

    • Fabián Segovia-Miranda
    • , Hernán Morales-Navarrete
    • , Michael Kücken
    • , Vincent Moser
    • , Sarah Seifert
    • , Urska Repnik
    • , Fabian Rost
    • , Mario Brosch
    • , Alexander Hendricks
    • , Sebastian Hinz
    • , Christoph Röcken
    • , Dieter Lütjohann
    • , Yannis Kalaidzidis
    • , Clemens Schafmayer
    • , Lutz Brusch
    • , Jochen Hampe
    •  & Marino Zerial
  • Article |

    The first BCL-XL-degrading PROTAC achieves safer and more potent antitumor activity than dual BCL-XL and BCL-2 inhibitor navitoclax because of reduced dose-limiting platelet toxicity and high target specificity.

    • Sajid Khan
    • , Xuan Zhang
    • , Dongwen Lv
    • , Qi Zhang
    • , Yonghan He
    • , Peiyi Zhang
    • , Xingui Liu
    • , Dinesh Thummuri
    • , Yaxia Yuan
    • , Janet S. Wiegand
    • , Jing Pei
    • , Weizhou Zhang
    • , Abhisheak Sharma
    • , Christopher R. McCurdy
    • , Vinitha M. Kuruvilla
    • , Natalia Baran
    • , Adolfo A. Ferrando
    • , Yong-mi Kim
    • , Anna Rogojina
    • , Peter J. Houghton
    • , Guangcun Huang
    • , Robert Hromas
    • , Marina Konopleva
    • , Guangrong Zheng
    •  & Daohong Zhou
  • Article |

    Ultra-sensitive cell-free DNA (cfDNA) sequencing uncovers clonal hematopoiesis as a major source of somatic cfDNA variants in healthy individuals and patients with cancer, and underscores the importance of matched white blood cell DNA sequencing in liquid biopsy procedures.

    • Pedram Razavi
    • , Bob T. Li
    • , David N. Brown
    • , Byoungsok Jung
    • , Earl Hubbell
    • , Ronglai Shen
    • , Wassim Abida
    • , Krishna Juluru
    • , Ino De Bruijn
    • , Chenlu Hou
    • , Oliver Venn
    • , Raymond Lim
    • , Aseem Anand
    • , Tara Maddala
    • , Sante Gnerre
    • , Ravi Vijaya Satya
    • , Qinwen Liu
    • , Ling Shen
    • , Nicholas Eattock
    • , Jeanne Yue
    • , Alexander W. Blocker
    • , Mark Lee
    • , Amy Sehnert
    • , Hui Xu
    • , Megan P. Hall
    • , Angie Santiago-Zayas
    • , William F. Novotny
    • , James M. Isbell
    • , Valerie W. Rusch
    • , George Plitas
    • , Alexandra S. Heerdt
    • , Marc Ladanyi
    • , David M. Hyman
    • , David R. Jones
    • , Monica Morrow
    • , Gregory J. Riely
    • , Howard I. Scher
    • , Charles M. Rudin
    • , Mark E. Robson
    • , Luis A. Diaz Jr.
    • , David B. Solit
    • , Alexander M. Aravanis
    •  & Jorge S. Reis-Filho
  • News & Views |

    Ultra-deep sequencing of paired plasma-circulating free DNA and white blood cells allows the identification of tumor-derived somatic mutations with high accuracy by filtering out variants consistent with clonal hematopoiesis.

    • Beatriz Bellosillo
    •  & Clara Montagut
  • Comment |

    With the growing number of efficient gene therapies on the market, now is the time to take actions to ensure reasonable pricing of gene therapy products. Among these, we propose to incentivize gene therapy companies to adopt a status that translates their corporate social responsibility into concrete commitments.

    • Alain Fischer
    • , Mathias Dewatripont
    •  & Michel Goldman
  • Letter |

    A new assay combining genotypic and phenotypic information accelerates accurate clinical antibiotic susceptibility testing.

    • Roby P. Bhattacharyya
    • , Nirmalya Bandyopadhyay
    • , Peijun Ma
    • , Sophie S. Son
    • , Jamin Liu
    • , Lorrie L. He
    • , Lidan Wu
    • , Rustem Khafizov
    • , Rich Boykin
    • , Gustavo C. Cerqueira
    • , Alejandro Pironti
    • , Robert F. Rudy
    • , Milesh M. Patel
    • , Rui Yang
    • , Jennifer Skerry
    • , Elizabeth Nazarian
    • , Kimberly A. Musser
    • , Jill Taylor
    • , Virginia M. Pierce
    • , Ashlee M. Earl
    • , Lisa A. Cosimi
    • , Noam Shoresh
    • , Joseph Beechem
    • , Jonathan Livny
    •  & Deborah T. Hung
  • Brief Communication |

    Inhibition of CSF-1R with recurrent activating alterations and other actionable targets identified by genomic sequencing elicits clinical activity in patients with histiocytosis.

    • Benjamin H. Durham
    • , Estibaliz Lopez Rodrigo
    • , Jennifer Picarsic
    • , David Abramson
    • , Veronica Rotemberg
    • , Steven De Munck
    • , Erwin Pannecoucke
    • , Sydney X. Lu
    • , Alessandro Pastore
    • , Akihide Yoshimi
    • , Diana Mandelker
    • , Ozge Ceyhan-Birsoy
    • , Gary A. Ulaner
    • , Michael Walsh
    • , Mariko Yabe
    • , Kseniya Petrova-Drus
    • , Maria E. Arcila
    • , Marc Ladanyi
    • , David B. Solit
    • , Michael F. Berger
    • , David M. Hyman
    • , Mario E. Lacouture
    • , Caroline Erickson
    • , Ruth Saganty
    • , Michelle Ki
    • , Ira J. Dunkel
    • , Vicente Santa-María López
    • , Jaume Mora
    • , Julien Haroche
    • , Jean-Francois Emile
    • , Olivier Decaux
    • , Frederic Geissmann
    • , Savvas N. Savvides
    • , Alexander Drilon
    • , Eli L. Diamond
    •  & Omar Abdel-Wahab
  • Author Correction |

    • Aparna R. Parikh
    • , Ignaty Leshchiner
    • , Liudmila Elagina
    • , Lipika Goyal
    • , Chaya Levovitz
    • , Giulia Siravegna
    • , Dimitri Livitz
    • , Kahn Rhrissorrakrai
    • , Elizabeth E. Martin
    • , Emily E. Van Seventer
    • , Megan Hanna
    • , Kara Slowik
    • , Filippo Utro
    • , Christopher J. Pinto
    • , Alicia Wong
    • , Brian P. Danysh
    • , Ferran Fece de la Cruz
    • , Isobel J. Fetter
    • , Brandon Nadres
    • , Heather A. Shahzade
    • , Jill N. Allen
    • , Lawrence S. Blaszkowsky
    • , Jeffrey W. Clark
    • , Bruce Giantonio
    • , Janet E. Murphy
    • , Ryan D. Nipp
    • , Eric Roeland
    • , David P. Ryan
    • , Colin D. Weekes
    • , Eunice L. Kwak
    • , Jason E. Faris
    • , Jennifer Y. Wo
    • , François Aguet
    • , Ipsita Dey-Guha
    • , Mehlika Hazar-Rethinam
    • , Dora Dias-Santagata
    • , David T. Ting
    • , Andrew X. Zhu
    • , Theodore S. Hong
    • , Todd R. Golub
    • , A. John Iafrate
    • , Viktor A. Adalsteinsson
    • , Alberto Bardelli
    • , Laxmi Parida
    • , Dejan Juric
    • , Gad Getz
    •  & Ryan B. Corcoran
  • Letter |

    Pluripotent stem cells can generate functional lungs when injected into blastocyst-stage mouse embryos, a step toward the goal of growing human lungs in large animals for disease modeling and therapeutic applications.

    • Munemasa Mori
    • , Kazuhiro Furuhashi
    • , Jennifer A. Danielsson
    • , Yuichi Hirata
    • , Miwako Kakiuchi
    • , Chyuan-Sheng Lin
    • , Mayu Ohta
    • , Paul Riccio
    • , Yusuke Takahashi
    • , Xinjing Xu
    • , Charles W. Emala
    • , Chao Lu
    • , Hiromitsu Nakauchi
    •  & Wellington V. Cardoso
  • Comment |

    Cardiometabolic disease is the leading cause of death and disability in the world, driven in part by the rise in unhealthy diets, poor air quality and other byproducts of economic development. A new economic model is needed, one that places people rather than profits at its center.

    • Johanna Ralston
    •  & Rachel Nugent
  • Editorial |

    The rise in cardiometabolic diseases is linked to the availability of unhealthy products from industry, such as ultraprocessed foods, and studying the efficacy of intervention strategies against these products must be high on the research agenda.

  • Letter |

    Epigenetic regulators modulating chromatin accessibility dictate sensitivity to anthracycline-based therapy in early breast cancer and represent potential biomarkers for patient stratification.

    • Jose A. Seoane
    • , Jacob G. Kirkland
    • , Jennifer L. Caswell-Jin
    • , Gerald R. Crabtree
    •  & Christina Curtis
  • News & Views |

    New findings regarding the risks of over-the-counter probiotics in critically ill patients underscore the need for microbiota-targeted therapies that are based on efficacy in a disease- and host-specific context.

    • Bastiaan W. Haak
    •  & W. Joost Wiersinga