• Article
    | Open Access

    A large-scale metagenomic analysis of plant and mammal environmental DNA reveals complex ecological changes across the circumpolar region over the past 50,000 years, as biota responded to changing climates, culminating in the postglacial extinction of large mammals and emergence of modern ecosystems.

    • Yucheng Wang
    • , Mikkel Winther Pedersen
    •  & Eske Willerslev
  • Article
    | Open Access

    Whole-exome sequencing analysis of 454,787 individuals in the UK Biobank is used to examine the association of protein-coding variants with nearly 4,000 health-related traits, identifying 564 distinct genes with significant trait associations.

    • Joshua D. Backman
    • , Alexander H. Li
    •  & Manuel A. R. Ferreira
  • Article |

    NanoSeq is used to detect mutations in single DNA molecules and analyses show that mutational processes that are independent of cell division are important contributors to somatic mutagenesis.

    • Federico Abascal
    • , Luke M. R. Harvey
    •  & Iñigo Martincorena
  • Article
    | Open Access

    The goals, resources and design of the NHLBI Trans-Omics for Precision Medicine (TOPMed) programme are described, and analyses of rare variants detected in the first 53,831 samples provide insights into mutational processes and recent human evolutionary history.

    • Daniel Taliun
    • , Daniel N. Harris
    •  & Gonçalo R. Abecasis
  • Article |

    Time-resolved RNA–protein cross-linking with a pulsed femtosecond ultraviolet laser, followed by immunoprecipitation and high-throughput sequencing, enables the determination of binding and dissociation kinetics of the RNA-binding protein DAZL within cells.

    • Deepak Sharma
    • , Leah L. Zagore
    •  & Eckhard Jankowsky
  • Article |

    A comprehensive map of transcriptomes, cis-regulatory elements, heterochromatin structure, the methylome and 3D genome organization in the zebrafish (Danio rerio) enables identification of species-specific and evolutionarily conserved regulatory features, and provides a foundation for modelling studies on human disease and development.

    • Hongbo Yang
    • , Yu Luan
    •  & Feng Yue
  • Article |

    Whole-genome sequencing analyses of African populations provide insights into continental migration, gene flow and the response to human disease, highlighting the importance of including diverse populations in genomic analyses to understand human ancestry and improve health.

    • Ananyo Choudhury
    • , Shaun Aron
    •  & Neil A. Hanchard
  • Article
    | Open Access

    High-coverage, ultra-long-read nanopore sequencing is used to create a new human genome assembly that improves on the coverage and accuracy of the current reference (GRCh38) and includes the gap-free, telomere-to-telomere sequence of the X chromosome.

    • Karen H. Miga
    • , Sergey Koren
    •  & Adam M. Phillippy
  • Article |

    A method termed ac4C-seq is introduced for the transcriptome-wide mapping of the RNA modification N4-acetylcytidine, revealing widespread temperature-dependent acetylation that facilitates thermoadaptation in hyperthermophilic archaea.

    • Aldema Sas-Chen
    • , Justin M. Thomas
    •  & Schraga Schwartz
  • Article |

    Thousands of sperm genomes have been analysed with a new method called Sperm-seq, revealing interconnected meiotic variation at the single-cell and person-to-person levels, and suggesting chromosome compaction as a way to explain the relationships between diverse recombination phenotypes.

    • Avery Davis Bell
    • , Curtis J. Mello
    •  & Steven A. McCarroll
  • Article |

    Single-cell RNA sequencing and spatial transcriptomics reveal that the somitogenesis clock is active in mouse gastruloids, which can be induced to generate somites with the correct rostral–caudal patterning.

    • Susanne C. van den Brink
    • , Anna Alemany
    •  & Alexander van Oudenaarden
  • Article |

    Single-cell transcriptomic profiling of fetal liver, skin, kidney and yolk sac reveals the differentiation trajectories of human haematopoietic stem cells and multipotent progenitors, which are validated to produce an integrated map of fetal liver haematopoiesis.

    • Dorin-Mirel Popescu
    • , Rachel A. Botting
    •  & Muzlifah Haniffa
  • Article
    | Open Access

    Exome-sequencing analyses of a large cohort of patients with type 2 diabetes and control individuals without diabetes from five ancestries are used to identify gene-level associations of rare variants that are associated with type 2 diabetes.

    • Jason Flannick
    • , Josep M. Mercader
    •  & Michael Boehnke
  • Article |

    Combinatorial tagging of single cells using expressed DNA barcodes, delivered by a lentiviral vector, is used to track individual cells and reconstruct their lineages and trajectories during cell fate reprogramming.

    • Brent A. Biddy
    • , Wenjun Kong
    •  & Samantha A. Morris
  • Letter
    | Open Access

    Long-read sequencing allows the assembly of antigen-gene arrays in Trypanosoma brucei and, coupled with deletion experiments, demonstrates that histone variants act as a molecular link between genome architecture, chromatin conformation and antigen variation.

    • Laura S. M. Müller
    • , Raúl O. Cosentino
    •  & T. Nicolai Siegel
  • Article |

    A large-scale genomics study shows that the cell of origin and founding mutations determine disease subtype and lead to the expression of multiple haematopoietic lineage-defining antigens in mixed phenotype acute leukaemia.

    • Thomas B. Alexander
    • , Zhaohui Gu
    •  & Charles G. Mullighan
  • Letter |

    Genetic similarity among late Neanderthals is predicted well by their geographical location, and although some of these Neanderthals were contemporaneous with early modern humans, their genomes show no evidence of recent gene flow from modern humans.

    • Mateja Hajdinjak
    • , Qiaomei Fu
    •  & Janet Kelso
  • Letter |

    Genome sequencing analyses from 765 specimens of Anopheles gambiae and Anopheles coluzzii from 15 locations across Africa characterize patterns of gene flow and variations in population size, and provide a resource for studying the evolution of natural malaria vector populations.

    • Alistair Miles
    • , Nicholas J. Harding
    •  & Dominic P. Kwiatkowski
  • Letter
    | Open Access

    The authors show that rare genetic variants contribute to large gene expression changes across diverse human tissues and provide an integrative method for interpretation of rare variants in individual genomes.

    • Xin Li
    • , Yungil Kim
    •  & Stephen B. Montgomery
  • Review Article |

    The history and future potential of DNA sequencing, including the development of the underlying technologies and the expansion of its areas of application, are reviewed.

    • Jay Shendure
    • , Shankar Balasubramanian
    •  & Robert H. Waterston
  • Letter |

    One hundred and ten Zika virus genomes from ten countries and territories involved in the Zika virus epidemic reveal rapid expansion of the epidemic within Brazil and multiple introductions to other regions.

    • Hayden C. Metsky
    • , Christian B. Matranga
    •  & Pardis C. Sabeti
  • Letter |

    Gene expression analysis in brain tissue from individuals with and without autism spectrum disorder (ASD) suggests that the transcription factor SOX5 contributes to an ASD-associated reduction in transcriptional differences between brain areas and indicates that common transcriptomic changes occur in different forms of ASD.

    • Neelroop N. Parikshak
    • , Vivek Swarup
    •  & Daniel H. Geschwind
  • Letter |

    Here, the selection of substrates by the protein–RNA complex known as the signal recognition particle (SRP) is investigated in the bacterium Escherichia coli, revealing that the SRP has a strong preference for hydrophobic transmembrane domains of inner membrane proteins.

    • Daniela Schibich
    • , Felix Gloge
    •  & Günter Kramer
  • Letter |

    A translation complex sequencing approach has been developed enabling intermediates of all mRNA-associated processes of translation to be isolated and localized across the transcriptome; the results support longstanding models of initiation and termination and offer new mechanistic insights.

    • Stuart K. Archer
    • , Nikolay E. Shirokikh
    •  & Thomas Preiss
  • Article |

    Sequencing data from two large-scale studies show that most of the genetic variation influencing the risk of type 2 diabetes involves common alleles and is found in regions previously identified by genome-wide association studies, clarifying the genetic architecture of this disease.

    • Christian Fuchsberger
    • , Jason Flannick
    •  & Mark I. McCarthy
  • Article |

    The prevalence of N6-adenine DNA methylation in mammals was previously unknown; this study reveals that N6-methyladenine can be found in mouse embryonic stem cells, especially at subfamilies of young (<1.5 million years old) LINE-1 transposons.

    • Tao P. Wu
    • , Tao Wang
    •  & Andrew Z. Xiao
  • Letter |

    Tumours can require certain amino acids for their proliferation, and the diricore method described here helps to identify such restrictive amino acids; using this method in kidney cancer tissue and breast carcinoma cells, the authors observe an association between proline deficiency and upregulation of PYCR1, an enzyme required for proline synthesis.

    • Fabricio Loayza-Puch
    • , Koos Rooijers
    •  & Reuven Agami
  • Letter |

    A nanopore DNA sequencer is used for real-time genomic surveillance of the Ebola virus epidemic in the field in Guinea; the authors demonstrate that it is possible to pack a genomic surveillance laboratory in a suitcase and transport it to the field for on-site virus sequencing, generating results within 24 hours of sample collection.

    • Joshua Quick
    • , Nicholas J. Loman
    •  & Miles W. Carroll