Browse Articles

  • Review Article |

    Gene expression is subjected to various random processes (referred to as ‘noise’) that contribute to variability in molecular phenotypes. As Eling, Morgan and Marioni describe, there are various challenges to studying this variability, such as disentangling its multilayered sources, distinguishing it from deterministic influences on cellular variability, modelling it with appropriate statistical methods and understanding its practical consequences.

    • Nils Eling
    • , Michael D. Morgan
    •  & John C. Marioni
  • Research Highlight |

    A study in Nature describes a CRISPR–Cas9-based ‘molecular recorder’ that can report on cellular state and cell lineage, in mice, from fertilization through to adulthood.

    • Katharine H. Wrighton
  • Research Highlight |

    A study in Cell incorporates metabolic networks into a machine-learning approach to provide mechanistic insights into bacterial antibiotic lethality.

    • Darren J. Burgess
  • Editorial |

    Genomics has transformed the field of microbiology, but remaining challenges will need to be tackled for its benefits to be felt globally.

  • Research Highlight |

    A study in Science uses experimental and population genomic approaches to examine the molecular underpinnings of evolved pollution resistance in Gulf killifish.

    • Linda Koch
  • Review Article |

    For appropriate control of gene expression, enhancers must communicate with the right target genes at the right time, typically over large genomic distances. In this Review, Schoenfelder and Fraser discuss our latest understanding of long-range enhancer–promoter crosstalk, including target-gene specificity, interaction dynamics, protein and RNA architects of interactions, roles of 3D genome organization and the pathological consequences of regulatory rewiring.

    • Stefan Schoenfelder
    •  & Peter Fraser
  • Research Highlight |

    A study of ancient horse genomes, described in Cell, reveals the existence of two now-extinct horse lineages and shows that modern breeding practices reduced genetic diversity in horses.

    • Katharine H. Wrighton
  • Review Article |

    Throughout evolution, DNA has been the primary medium of biological information storage. In this article, Ceze, Nivala and Strauss discuss how DNA can be adopted as a storage medium for custom data, as a potential future complement to current data storage media such as computer hard disks, optical disks and tape. They discuss strategies for coding, decoding and error correction and give examples of implementation both in vitro and in vivo.

    • Luis Ceze
    • , Jeff Nivala
    •  & Karin Strauss
  • Review Article |

    Despite the success of human genome-wide association studies (GWAS) in associating genetic variants and complex diseases or traits, criticisms of the usefulness of this study design remain. This Review assesses the pros and cons of GWAS, with a focus on the cardiometabolic field.

    • Vivian Tam
    • , Nikunj Patel
    • , Michelle Turcotte
    • , Yohan Bossé
    • , Guillaume Paré
    •  & David Meyre
  • Research Highlight |

    A new study reports a genome-wide polygenic score (GPS) that is predictive of obesity, thus providing opportunities for early health interventions.

    • Darren J. Burgess
  • Research Highlight |

    An experimental evolution study published in Science demonstrates that non-additive interactions between pollinators (bumblebees) and herbivores (caterpillars) drive rapid evolution in plants.

    • Dorothy Clyde
  • Research Highlight |

    Two new spatial transcriptomics techniques published in Nature and Science bring us an important step closer to the goal of achieving transcriptome-wide data at single-cell resolution.

    • Darren J. Burgess
  • Research Highlight |

    Two meta-analyses of fecal metagenomics studies report the presence of a microbial signature that is predictive of colorectal cancer.

    • Linda Koch
  • Review Article |

    This article reviews recent advances in ancient pathogen genomics, from methodological improvements in retrieving whole genomes to evolutionary analyses of ancient pathogens that remain relevant to public health. Focusing on the evolutionary history of the plague pathogen Yersinia pestis, the authors present unique insights afforded by the study of ancient pathogen genomes.

    • Maria A. Spyrou
    • , Kirsten I. Bos
    • , Alexander Herbig
    •  & Johannes Krause
  • Research Highlight |

    A fuller understanding of bacterial genomic variation could provide insight into host pathophysiology. A new study in Nature demonstrates that structural variants are highly prevalent in human gut microbiomes and that some associate with host disease risk factors.

    • Dorothy Clyde
  • Research Highlight |

    A new study in Science reports the existence of a subpopulation of somatic cells from which ‘elite’ clones emerge that outperform other clones to drive reprogramming.

    • Linda Koch
  • Comment |

    The clinical application of genomic technologies is driving new discoveries that may be relevant to individuals who have previously undergone genetic testing. This Comment highlights the need for a framework to decide whether to recontact patients and inform them of new genetic findings.

    • Noor A. A. Giesbertz
    • , Wim H. van Harten
    •  & Annelien L. Bredenoord
  • Review Article |

    Clinical metagenomic next-generation sequencing (mNGS) is rapidly moving from bench to bedside. This Review discusses the clinical applications of mNGS, including infectious disease diagnostics, microbiome analyses, host response analyses and oncology applications. Moreover, the authors review the challenges that need to be overcome for mNGS to be successfully implemented in the clinical laboratory and propose solutions to maximize the benefits of clinical mNGS for patients.

    • Charles Y. Chiu
    •  & Steven A. Miller
  • Research Highlight |

    In a study in Nature Microbiology, Setoh et al. use deep mutational scanning to speed up viral evolution and identify key determinants of host tropism in Zika virus.

    • Dorothy Clyde
  • Review Article |

    Recent next-generation sequencing studies have captured the spatial and temporal evolutionary patterns that shape cancer. This Review provides an overview of the theoretical models of tumour evolution and discusses what to consider when inferring evolutionary dynamics from genomic data.

    • Samra Turajlic
    • , Andrea Sottoriva
    • , Trevor Graham
    •  & Charles Swanton
  • Research Highlight |

    Two studies report substantial temporal and spatial variability in mutagenic signatures caused by APOBEC cytidine deaminases in cancer.

    • Darren J. Burgess
  • Research Highlight |

    A study in Nature reveals that N6-methyladenosine (m6A) modification of RNA occurs co-transcriptionally and is mediated by interactions between histone H3 lysine 36 trimethylation (H3K36me3) and the m6A methyltransferase complex.

    • Dorothy Clyde
  • Perspective |

    Using the example of carbon concentrating mechanisms in plants, the authors of this Perspective provide evidence that broad comparative genomic analyses likely overestimate the genetic complexity underlying convergent evolution of complex traits.

    • Karolina Heyduk
    • , Jose J. Moreno-Villena
    • , Ian S. Gilman
    • , Pascal-Antoine Christin
    •  & Erika J. Edwards
  • Review Article |

    Eukaryotes differ substantially from bacteria and archaea owing to their nucleosome-based packaging of DNA. In this Review, Talbert, Meers and Henikoff place gene regulation in an evolutionary context by discussing how the emergence and diversification of eukaryotic chromatin provided both challenges and opportunities for intricate mechanisms of gene regulation in eukaryotes.

    • Paul B. Talbert
    • , Michael P. Meers
    •  & Steven Henikoff
  • Research Highlight |

    Nair et al. contrast events at specific super-enhancers after acute and chronic ligand-induced activation and show that biomolecular condensates at these enhancers undergo physical changes over time that affect chromatin conformation and gene expression.

    • Linda Koch
  • Review Article |

    Next-generation sequencing has improved the identification and characterization of antimicrobial resistance. Focusing on sequence-based discovery of antibiotic resistance genes, this Review discusses computational strategies and resources for resistance gene identification in genomic and metagenomic samples, including recent deep-learning approaches.

    • Manish Boolchandani
    • , Alaric W. D’Souza
    •  & Gautam Dantas
  • Comment |

    A genomics-informed response to infectious disease has great potential to improve individual patient treatment as well as public health. This Comment discusses the ethical, legal and social challenges that will need to be overcome if clinical pathogen genomics is to be implemented successfully.

    • Stephanie B. Johnson
    •  & Michael Parker
  • Comment |

    Variants of unknown significance (VUS) are genetic variants whose association with disease risk is unknown. The authors posit that VUS should not inform clinical decision-making as the benefits of returning this genetic information to patients undergoing genetic testing are outweighed by the potential for harm.

    • Samantha Pollard
    • , Sophie Sun
    •  & Dean A. Regier
  • Research Highlight |

    Two studies in Science show that cytosine base editors, but not adenine base editors or CRISPR–Cas9, induce notable off-target single-nucleotide variants in rice and in mouse embryos.

    • Katharine H. Wrighton
  • Review Article |

    Transposable elements (TEs) need to be tightly regulated in genomes to prevent the detrimental consequences of transposition. In this Review, Deniz, Frost and Branco discuss how DNA methylation dynamics play a central role in the multilayered epigenetic mechanisms regulating TEs. Beyond roles for 5-methylcytosine (5mC), they discuss TET-mediated oxidation products of 5mC, as well as ongoing debates about the functional relevance of adenine methylation.

    • Özgen Deniz
    • , Jennifer M. Frost
    •  & Miguel R. Branco
  • Research Highlight |

    Three new studies characterize circular RNAs in cancer, with potential functional roles and clinical implications as biomarkers.

    • Darren J. Burgess
  • Research Highlight |

    Chromosomal inversions that relocate a limb enhancer establish patterns of asymmetric chromatin contacts, so-called architectural stripes, that result in ectopic gene expression and congenital limb phenotypes, according to a study in Nature Cell Biology.

    • Michelle Trenkmann
  • Research Highlight |

    A new technique named ChIA-Drop combines chromatin interaction analysis (ChIA) with droplet-based and barcode-linked high-throughput sequencing to capture multiplex chromatin interactions at the single-molecule level.

    • Linda Koch
  • Perspective |

    In this Timeline article, Shay and Wright provide a historical account of progress in our understanding of telomeres (the ends of linear chromosomes) and telomerase (the primary enzyme that maintains and extends telomere lengths). Their perspective covers seminal moments from the early discoveries through to our latest understanding of the roles of telomeres and telomerase in ageing, diverse human diseases and gene regulation.

    • Jerry W. Shay
    •  & Woodring E. Wright
  • Review Article |

    Enthusiasm for patient-specific therapies based on induced pluripotent stem cells (iPSCs) has risen in parallel with rapid advances in genome editing. This Review summarizes the progress in iPSC-based disease modelling over the past decade, with a focus on 3D organoid systems and chimeric models being exploited for new therapeutic approaches.

    • R. Grant Rowe
    •  & George Q. Daley
  • Research Highlight |

    A study published in Nature reports the functional and structural characterization of CasX, an RNA-guided DNA endonuclease with potential for use as a new genome editing platform.

    • Linda Koch
  • Review Article |

    The functional interpretation of single-cell RNA sequencing (scRNA-seq) data can be enhanced by integrating additional data types beyond RNA-based gene expression. In this Review, Stuart and Satija discuss diverse approaches for integrative single-cell analysis, including experimental methods for profiling multiple omics types from the same cells, analytical approaches for extracting additional layers of information directly from scRNA-seq data and computational integration of omics data collected across different cell samples.

    • Tim Stuart
    •  & Rahul Satija
  • Research Highlight |

    A new study uses deep learning to predict genetic variants that generate cryptic splice sites and to investigate the role of these non-coding cryptic splice mutations in rare genetic disorders.

    • Dorothy Clyde
  • Research Highlight |

    Two studies in Developmental Cell report the generation of mice with longer and shorter than normal tails, respectively, giving insight into developmental programmes and key genes involved in mouse tail development.

    • Linda Koch
  • Review Article |

    Chromatin accessibility comprises the positions, compaction and dynamics of nucleosomes, as well as the occupancy of DNA by other proteins such as transcription factors. In this Review, the authors discuss diverse methods for characterizing chromatin accessibility, how accessibility is determined and remodelled in cells and the regulatory roles of accessibility in gene expression and development.

    • Sandy L. Klemm
    • , Zohar Shipony
    •  & William J. Greenleaf
  • Research Highlight |

    A new study published in Cell uses bacterial genetic screens to identify mutagenic proteins. Overexpression of homologues of these proteins in human cells has similar mutagenic effects and potential prognostic value in cancer.

    • Darren J. Burgess
  • Research Highlight |

    The BabySeq project, a pilot randomized clinical trial exploring the value of routine genomic sequencing of neonates compared with standard newborn screening, now reports initial results in the American Journal of Human Genetics.

    • Linda Koch
  • Review Article |

    Disruption of genomic imprinting can lead to disease. Recent studies suggest that interactions between the genome, the epigenome and the environment in germ cells and early embryos have an impact on developmental outcomes and on the heritability of imprinting disorders.

    • David Monk
    • , Deborah J. G. Mackay
    • , Thomas Eggermann
    • , Eamonn R. Maher
    •  & Andrea Riccio
  • Review Article |

    Comparing the microbiomes of great apes enables an evolutionary perspective on microbial communities. This approach is revealing not only new insights about humans and what differentiates us from our closest relatives but also the factors that influence microbiome composition and the ways in which microbiomes diverge.

    • Alex H. Nishida
    •  & Howard Ochman
  • Review Article |

    Single-cell RNA sequencing (scRNA-seq) enables transcriptome-based characterization of the constituent cell types within a heterogeneous sample. However, reliable analysis and biological interpretation typically require optimal use of clustering algorithms. This Review discusses the multiple algorithmic options for clustering scRNA-seq data, including various technical, biological and computational considerations.

    • Vladimir Yu Kiselev
    • , Tallulah S. Andrews
    •  & Martin Hemberg
  • Review Article |

    Understanding the fundamental impact of sex and gender on human health and disease is crucial for optimizing precision medicine. In this Review, Khramtsova, Davis and Stranger discuss the roles of sex in the genetics of complex traits, including genomic evidence for sex-dependent genetic architecture, models and molecular mechanisms of sexually differentiated phenotypes and implications for health care.

    • Ekaterina A. Khramtsova
    • , Lea K. Davis
    •  & Barbara E. Stranger