Reviews & Analysis

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  • Silver, Bick and Savona discuss our latest understanding of clonal haematopoiesis (CH), which is an expansion of blood cell populations with shared somatic mutations. They focus on human germline risk variants and on how these are linked to different forms of CH and their associated disease pathologies.

    • Alexander J. Silver
    • Alexander G. Bick
    • Michael R. Savona
    Review Article
  • This Review outlines how approaches from physics can be used to simplify and understand complex patterning events during development. In particular, wavefronts, genetic oscillators and genetic timers are discussed in the context of illustrative developmental processes.

    • Jose Negrete Jr
    • Andrew C. Oates
    Review Article
  • Population-scale testing is an essential component of responses to the COVID-19 pandemic and is likely to become increasingly important in public health. Here, Mercer and Salit describe the roles of testing during the COVID-19 pandemic, including in genomic surveillance, contact tracing and environmental testing.

    • Tim R. Mercer
    • Marc Salit
    Review Article
  • In this Perspective article, Oh and Petronis discuss emerging evidence of time-dependent patterns of DNA modification and describe how incorporating this ‘chrono-epigenetic’ perspective could add value and interpretability in human disease studies.

    • Edward Saehong Oh
    • Art Petronis
  • In this Perspective, Teschendorff and Feinberg describe how single-cell analysis methods based on statistical mechanics can provide valuable insights into developmental phenomena, such as differentiation potency and lineage trajectories, as well as disruption of these processes in cancer.

    • Andrew E. Teschendorff
    • Andrew P. Feinberg
  • In this Review, Neafsey, Taylor and MacInnis discuss how population genomics approaches are currently used to study malaria parasites and mosquito vectors. They explore information that can be derived from such genomics approaches and discuss the use of relatedness-based measures of population variation to understand parasite and vector dynamics at highly resolved spatiotemporal scales.

    • Daniel E. Neafsey
    • Aimee R. Taylor
    • Bronwyn L. MacInnis
    Review Article
  • The authors review the evidence for a biological role of RNA as a form of cell–cell communication in mammals as well as proposed roles for extracellular RNAs in health and disease. Moreover, this Review emphasizes and provides guidance on the experimental rigor that is required to definitively show that extracellular RNAs are functional in recipient cells in vivo.

    • Hannah N. Gruner
    • Michael T. McManus
    Review Article
  • Stapornwongkul and Vincent review models for morphogen gradient formation. They propose that hindered diffusion, in which interactions between morphogens and extracellular binders modulate gradient shape and dynamics, could form robust morphogen gradients in a variety of tissue contexts.

    • Kristina S. Stapornwongkul
    • Jean-Paul Vincent
    Review Article
  • Profiling tumours by next-generation sequencing can improve diagnostic accuracy, assess for heritable cancer risk and guide treatment selection. The authors review efforts to enhance the clinical utility of cancer genomic profiling through integrative analyses of tumour and germline variants, as well as by characterizing allelic context and mutational signatures that influence therapy response.

    • Debyani Chakravarty
    • David B. Solit
    Review Article
  • This Review discusses strategies for the genetic engineering of adoptive T cell immunotherapies with a focus on approaches harnessing transgenic T cell receptors or chimeric antigen receptors to treat cancer. The authors also discuss the more complex levels of genetic regulation that will be needed to ensure both safety and efficacy.

    • Gavin I. Ellis
    • Neil C. Sheppard
    • James L. Riley
    Review Article
  • Interactions between microorganisms and their hosts are highly context dependent and contribute to both normal tissue function and infectious disease pathology. In this Review, Westermann and Vogel describe how advances in RNA sequencing techniques are providing molecular insights into host–microbe interactions, including advances in cross-species and single-cell transcriptomics.

    • Alexander J. Westermann
    • Jörg Vogel
    Review Article
  • There is a rapidly growing appreciation of the complexities of 3D genome organization, as well as associations with gene expression and wider cellular and organismal phenotypes, including diseases. In this Review, the authors describe diverse experimental methods for manipulating 3D genome organization — from fine-scale control of DNA contacts to large-scale nuclear repositioning — which are facilitating detailed testing of the biological functions of 3D genome organization.

    • Haifeng Wang
    • Mengting Han
    • Lei S. Qi
    Review Article
  • Maintenance of cell-type identity requires the faithful inheritance of chromatin states through cell division, despite the challenges posed by the disruptive passage of the DNA replication fork and the dilution of nucleosome components in complex with the daughter DNA strands. In this Review, Escobar, Loyola and Reinberg discuss how methodological advances are providing unprecedented mechanistic insights into the segregation of parental nucleosomes, how these mechanisms maintain gene expression programmes and how non-faithful nucleosome segregation is linked to differentiation and disease.

    • Thelma M. Escobar
    • Alejandra Loyola
    • Danny Reinberg
    Review Article
  • MicroRNAs (miRNA) exert essential functions in mammalian development and physiology. The authors review recent insights from the phenotypic analysis of miRNA knockouts in mice that emphasize roles for these non-coding RNAs at different developmental stages and in adults, and illustrate the importance of functional miRNA targets, miRNA dosage, miRNA interactions and cellular context.

    • Brian DeVeale
    • Jennifer Swindlehurst-Chan
    • Robert Blelloch
    Review Article
  • Shadow enhancers regulate a common target gene and drive expression patterns that overlap spatiotemporally. The authors review recent insights into the prevalence and role of shadow enhancers in metazoans, as well as their mechanisms of action to fine-tune gene expression. They also discuss the evolution of shadow enhancers and their implication in disease.

    • Evgeny Z. Kvon
    • Rachel Waymack
    • Zeba Wunderlich
    Review Article
  • Africa is a continent with deep evolutionary history, which has implications for the genetic underpinnings of disease. In this Review, the authors discuss how genetic features of African populations provide both challenges and opportunities for understanding disease genetics in Africa. They describe how this genetic knowledge — combined with initiatives including capacity-building, data sharing and increased representation of African genomes in genetic variation databases — can be leveraged towards achieving precision medicine approaches in African healthcare.

    • Luisa Pereira
    • Leon Mutesa
    • Michèle Ramsay
    Review Article
  • Our evolutionary history has resulted in highly complex and sophisticated human physiology. Yet evolutionary footprints have also left us prone to diseases. In this Review, the authors discuss how events from the earliest history of life on Earth through to modern human evolution influence many disease traits and outcomes. They describe how an understanding and application of evolutionary frameworks can inform precision medicine initiatives.

    • Mary Lauren Benton
    • Abin Abraham
    • John A. Capra
    Review Article
  • The ability to reprogramme cellular translation and genomes to produce non-canonical biopolymers has wide-ranging applications, including in therapeutics, but has yet to be fully realized. In this Review, de la Torre and Chin discuss recent advances towards achieving this goal.

    • Daniel de la Torre
    • Jason W. Chin
    Review Article
  • Haematopoietic stem and progenitor cell (HSPC) gene therapy using lentiviral or gammaretroviral vectors has now been approved for clinical use. In this Review, Ferrari, Thrasher and Aiuti discuss the history of HSPC gene therapy, the clinical promise of gene-editing HPSCs and the use of HSPC gene therapy to treat specific diseases.

    • Giuliana Ferrari
    • Adrian J. Thrasher
    • Alessandro Aiuti
    Review Article
  • Infectious diseases are an ever-present global threat. In this Review, Kwok, Mentzer and Knight discuss our latest understanding of how human genetics influence susceptibility to disease. Furthermore, they discuss emerging progress in the interplay between host and pathogen genetics, molecular responses to infection and vaccination, and opportunities to bring these aspects together for rapid responses to emerging diseases such as COVID-19.

    • Andrew J. Kwok
    • Alex Mentzer
    • Julian C. Knight
    Review Article