Reviews & Analysis

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  • Large-scale genetic datasets and deep learning approaches are being used to model the structures of proteins or protein complexes. This Review describes approaches based on coevolution, deep mutational scanning and genome-scale genetic or chemical–genetic interaction mapping and their application and integration to inform structural modelling.

    • Hannes Braberg
    • Ignacia Echeverria
    • Nevan J. Krogan
    Review Article
  • Synthetic RNA devices integrate sensing, processing and actuation of signals into defined, programmable functions to control cell behaviour. This Review discusses the emerging applications of RNA devices in biomedical research and biomanufacturing, as well as progress in creating new ligand sensors and new mechanisms of action with engineered RNAs.

    • Peter B. Dykstra
    • Matias Kaplan
    • Christina D. Smolke
    Review Article
  • RNA therapies can be used to manipulate gene expression or produce therapeutic proteins. Here, the authors describe the growing number of RNA therapies and their molecular mechanisms of action. They also discuss the path from preclinical drug delivery research to clinical approval of these drugs.

    • Kalina Paunovska
    • David Loughrey
    • James E. Dahlman
    Review Article
  • In this Review the authors provide an overview of key algorithmic developments, popular tools and emerging technologies used in the bioinformatic analysis of genomes. They also describe how such analysis can identify point mutations, copy number alterations, structural variations and mutational signatures in cancer genomes.

    • Isidro Cortés-Ciriano
    • Doga C. Gulhan
    • Peter J. Park
    Review Article
  • The authors review the field of mammalian mitochondrial genome engineering, culminating in the recent development of mitochondrially targeted programmable nucleases and base editors. They describe research that led to the development of animal models of mitochondrial disease, as well as the potential for translating these approaches to the clinic.

    • Pedro Silva-Pinheiro
    • Michal Minczuk
    Review Article
  • Loci that encode long non-coding RNAs (lncRNAs) can be complex and function through multiple modalities. The authors provide a framework for elucidating the physiological roles of lncRNAs using genetically engineered mouse models, including whole-gene deletion, transcription termination, reporters and transgene rescue strategies.

    • Daniel Andergassen
    • John L. Rinn
    Review Article
  • Machine learning is widely applied in various fields of genomics and systems biology. In this Review, the authors describe how responsible application of machine learning requires an understanding of several common pitfalls that users should be aware of (and mitigate) to avoid unreliable results.

    • Sean Whalen
    • Jacob Schreiber
    • Katherine S. Pollard
    Review Article
  • In this Review, the authors discuss explanations for why ultraconserved sequences — which are presumed to be functionally crucial on the basis of strong evolutionary constraint — often result in surprisingly minor phenotypic consequences when experimentally disrupted. They also discuss the wider implications of extreme non-coding conservation for understanding the mechanisms of gene regulation and human variant interpretation.

    • Valentina Snetkova
    • Len A. Pennacchio
    • Diane E. Dickel
    Review Article
  • This Perspective highlights privacy issues related to the sharing of functional genomics data, including genotype and phenotype information leakage from different functional genomics data types and their summarization steps. The authors also review the techniques that will enable broad sharing and analysis while maintaining privacy.

    • Gamze Gürsoy
    • Tianxiao Li
    • Mark B. Gerstein
    Perspective
  • Hologenomic studies aim to further our understanding of host–microbiota interactions through the integrated analysis of host genomes and microbiota metagenomes. Here, Alberdi and colleagues discuss key considerations for designing optimal hologenomic studies and outline important biological questions that these studies can address.

    • Antton Alberdi
    • Sandra B. Andersen
    • M. Thomas P. Gilbert
    Review Article
  • The authors review overlapping sequences as fundamental features of prokaryotic, eukaryotic and viral genomes, discussing the diverse topologies and functions of overlapping genes, open reading frames and coding sequences. Moreover, they highlight the potential of harnessing sequence overlaps for synthetic biology approaches.

    • Bradley W. Wright
    • Mark P. Molloy
    • Paul R. Jaschke
    Review Article
  • In this Review, Janssen and Lorincz discuss the intricate and multilayered interplay between chromatin marks. Focusing on histone methylation and DNA methylation during mammalian development, they discuss the implications for gene regulation, differentiation and human disease.

    • Sanne M. Janssen
    • Matthew C. Lorincz
    Review Article
  • In this Review, Zhang et al. summarize our current understanding of the molecular mechanisms underlying the responses of plants to abiotic stresses, and how this knowledge can be used to improve crop resilience through genetic, chemical and microbial approaches.

    • Huiming Zhang
    • Jianhua Zhu
    • Jian-Kang Zhu
    Review Article
  • In this Review, Loos and Yeo summarize our current understanding of the genetic underpinnings of monogenic and polygenic obesity. They highlight the commonalities revealed by recent studies and discuss the implications for treatment and prediction of obesity risk.

    • Ruth J. F. Loos
    • Giles S. H. Yeo
    Review Article
  • In this Review, Przybyla and Gilbert describe the latest approaches for CRISPR-based functional genomics screens, including the adoption of single-cell transcriptomic read-outs and applications in characterizing the non-coding genome and mapping genetic interactions at scale.

    • Laralynne Przybyla
    • Luke A. Gilbert
    Review Article
  • In this Review, Conine and Rando discuss, across species, the myriad examples of intercellular RNA trafficking from nurse cells or somatic tissues to developing gametes, and consider how intercellular RNA trafficking shapes the germline epigenome.

    • Colin C. Conine
    • Oliver J. Rando
    Review Article
  • In this Review, the authors describe our latest understanding of the emergence and properties of SARS-CoV-2 genetic variants, particularly those designated as WHO (World Health Organization) ‘variants of concern’. They focus on the consequences of these variants for antibody-mediated virus neutralization, with important implications for reinfection risk and for vaccine effectiveness.

    • Kaiming Tao
    • Philip L. Tzou
    • Robert W. Shafer
    Review Article
  • The authors review intra-individual and inter-individual plant epigenome variation during development and in response to environmental changes, including stress. They also discuss functions of epigenome plasticity and epigenome editing technologies that will drive future research.

    • James P. B. Lloyd
    • Ryan Lister
    Review Article
  • Regular physical activity reduces the risk of chronic disease and mortality, but the mechanisms underpinning this protective effect are poorly understood. Here, Kim et al. review candidate genes and pathways implicated in human performance by genetic, genomic and multi-omic studies.

    • Daniel Seung Kim
    • Matthew T. Wheeler
    • Euan A. Ashley
    Review Article