• Article
    | Open Access

    A cross-ancestry meta-analysis of genome-wide association studies identifies association signals for stroke and its subtypes at 89 (61 new) independent loci, reveals putative causal genes, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as potential drug targets, and provides cross-ancestry integrative risk prediction.

    • Aniket Mishra
    • , Rainer Malik
    •  & Stephanie Debette
  • Article |

    Targeted therapies matched to genomics improved progression-free survival when genomic alterations were classified as level I/II (according to ESCAT), and genomics should thus be driven by target actionability in patients with metastatic breast cancer.

    • Fabrice Andre
    • , Thomas Filleron
    •  & Ivan Bieche
  • Article
    | Open Access

    Analyses of circulating cell-free RNA (cfRNA) in blood samples from pregnant mothers identify changes in gene expression that could be used in liquid biopsy tests to identify and monitor individuals who are at risk of preeclampsia.

    • Mira N. Moufarrej
    • , Sevahn K. Vorperian
    •  & Stephen R. Quake
  • Perspective |

    The Dog Aging Project is an open-data, community science study to identify genetic, environmental and lifestyle factors associated with canine healthy lifespan, generating knowledge that could readily translate to human ageing.

    • Kate E. Creevy
    • , Joshua M. Akey
    •  & Benjamin S. Wilfond
  • Article |

    A robust, cost-effective technique based on whole-exome sequencing data can be used to characterize immune infiltrates, relate the extent of these infiltrates to somatic changes in tumours, and enables prediction of tumour responses to immune checkpoint inhibition therapy.

    • Robert Bentham
    • , Kevin Litchfield
    •  & Nicholas McGranahan
  • Perspective |

    The LifeTime initiative is an ambitious, multidisciplinary programme that aims to improve healthcare by tracking individual human cells during disease processes and responses to treatment in order to develop and implement cell-based interceptive medicine in Europe.

    • Nikolaus Rajewsky
    • , Geneviève Almouzni
    •  & Frauke Zipp
  • Article |

    Microbial nucleic acids are detected in samples of tissues and blood from more than 10,000 patients with cancer, and machine learning is used to show that these can be used to discriminate between and among different types of cancer, suggesting a new microbiome-based diagnostic approach.

    • Gregory D. Poore
    • , Evguenia Kopylova
    •  & Rob Knight
  • Article |

    Multiomic profiling of several cohorts of patients treated with immune checkpoint blockade highlights the presence and potential role of B cells and tertiary lymphoid structures in promoting therapy response.

    • Beth A. Helmink
    • , Sangeetha M. Reddy
    •  & Jennifer A. Wargo
  • Article |

    Immune profiling of the tumour microenvironment of soft-tissue sarcoma identifies a group of patients with high levels of B-cell infiltration and tertiary lymphoid structures that have improved survival and a high response rate to immune checkpoint blockade therapy.

    • Florent Petitprez
    • , Aurélien de Reyniès
    •  & Wolf H. Fridman
  • Article
    | Open Access

    Deep profiling of transcriptomes, metabolomes, cytokines, and proteomes, alongside changes in the microbiome, in samples from individuals with and without prediabetes reveal insights into inter-individual variability and associations between changes in the microbiome and other factors.

    • Wenyu Zhou
    • , M. Reza Sailani
    •  & Michael Snyder
  • Letter |

    In a phase I trial, highly individualized peptide vaccines against unmutated tumour antigens and neoepitopes elicited sustained responses in CD8+ and CD4+ T cells, respectively, in patients with newly diagnosed glioblastoma.

    • Norbert Hilf
    • , Sabrina Kuttruff-Coqui
    •  & Wolfgang Wick
  • Article |

    Analyses of samples from patients with acute myeloid leukaemia reveal that drug response is associated with mutational status and gene expression; the generated dataset provides a basis for future clinical and functional studies of this disease.

    • Jeffrey W. Tyner
    • , Cristina E. Tognon
    •  & Brian J. Druker
  • Article
    | Open Access

    Analyses of genomes from 914 children, adolescents, and young adults provide a comprehensive resource of genomic alterations across a spectrum of common childhood cancers.

    • Susanne N. Gröbner
    • , Barbara C. Worst
    •  & Stefan M. Pfister
  • Letter |

    In humans, TGFβ signalling is associated with lack of response to immunotherapy in immune-excluded tumours; in mouse models of this immune phenotype, robust tumour infiltration by T cells and tumour regression are observed only when checkpoint inhibition is combined with inhibition of TGFβ signalling.

    • Sanjeev Mariathasan
    • , Shannon J. Turley
    •  & Thomas Powles
  • Article |

    Circulating tumour DNA profiling in early-stage non-small-cell lung cancer can be used to track single-nucleotide variants in plasma to predict lung cancer relapse and identify tumour subclones involved in the metastatic process.

    • Christopher Abbosh
    • , Nicolai J. Birkbak
    •  & Charles Swanton
  • Article |

    Genomic analyses of localized, non-indolent prostate cancer identify recurrent aberrations that can predict relapse, and also highlight differences between early prostate cancer and metastatic, castration-resistant disease.

    • Michael Fraser
    • , Veronica Y. Sabelnykova
    •  & Paul C. Boutros
  • Letter |

    A rapid gene signature test (LSC17) that captures stem cell expression programs in acute myeloid leukaemia patients at diagnosis is associated with therapy response and survival, facilitating initial treatment stratification.

    • Stanley W. K. Ng
    • , Amanda Mitchell
    •  & Jean C. Y. Wang
  • Brief Communications Arising |

    • Zhaleh Safikhani
    • , Nehme El-Hachem
    •  & Benjamin Haibe-Kains
  • Letter |

    In a mouse model of ischaemia, mitochondrial particles released from astroctyes are taken up by adjacent neurons, leading to enhanced cell survival signalling; disruption of this release mechanism resulted in worsened neurological outcomes.

    • Kazuhide Hayakawa
    • , Elga Esposito
    •  & Eng H. Lo
  • Brief Communications Arising |

    • Nan Qin
    • , Emmanuelle Le Chatelier
    •  & S. Dusko Ehrlich
  • Article |

    Glypican-1 identifies cancer exosomes and serves as a biomarker for detection of early pancreatic cancer in patients and mouse models of the disease; the findings may enable early and non-invasive identification, and prevention of malignant cancer.

    • Sonia A. Melo
    • , Linda B. Luecke
    •  & Raghu Kalluri
  • Letter |

    Many factors have been proposed as contributors to risk of alcohol abuse, but quantifying their influence has been difficult; here a longitudinal study of a large sample of adolescents and machine learning are used to generate models of predictors of current and future alcohol abuse, assessing the relative contribution of many factors, including life history, individual personality differences, brain structure and genotype.

    • Robert Whelan
    • , Richard Watts
    •  & Veronika Ziesch.
  • Article
    | Open Access

    This paper reports integrative molecular analyses of urothelial bladder carcinoma at the DNA, RNA, and protein levels performed as part of The Cancer Genome Atlas project; recurrent mutations were found in 32 genes, including those involved in cell-cycle regulation, chromatin regulation and kinase signalling pathways; chromatin regulatory genes were more frequently mutated in urothelial carcinoma than in any other common cancer studied so far.

    • John N. Weinstein
    • , Rehan Akbani
    •  & Greg Eley
  • Perspective
    | Open Access

    A checklist of criteria to determine the readiness of high-throughput ‘omics’-based tests for guiding patient therapy in clinical trials is discussed; the checklist, developed by the US National Cancer Institute in collaboration with additional scientists with relevant expertise, provides a framework to evaluate the strength of evidence for a test and outlines practical issues to consider before using the test in a clinical setting, with an aim to avoid premature advancement of omics-based tests in clinical trials.

    • Lisa M. McShane
    • , Margaret M. Cavenagh
    •  & Barbara A. Conley
  • Letter |

    Exploration of the interacting effect of statin exposure and genetic variation on gene expression identifies a cis-eQTL that is differentially associated with expression of the GATM gene, which encodes a rate-limiting enzyme involved in creatine synthesis, and that is associated with incidence of statin-induced myopathy, the major adverse effect of statin treatment.

    • Lara M. Mangravite
    • , Barbara E. Engelhardt
    •  & Ronald M. Krauss
  • Letter |

    The Cancer Cell Line Encyclopedia presents the first results from a large-scale screen of some 947 cancer cell lines with 24 anticancer drugs, with the aim of identifying specific genomic alterations and gene expression profiles associated with selective sensitivity or resistance to potential therapeutic agents.

    • Jordi Barretina
    • , Giordano Caponigro
    •  & Levi A. Garraway