Reviews & Analysis

Advances in long-read sequencing are driving the implementation of these technologies for transcriptome profiling. The authors provide a comprehensive guide to long-read RNA sequencing, including experimental and computational tools, current applications, challenges and opportunities.

Long-read sequencing technologies can directly profile methylation modifications across the genome. In this Review, Fu et al. overview the long-read computational tools to identify and compare methylation signals, as well as tools that use these methylation signals to analyse cell-type diversity and gain additional genomic insights.

This Review explores how experimental models of metastasis, such as mouse models and cell cultures, can complement the (multi)omics analysis of human metastasis samples, thereby filling knowledge gaps left by model studies and validating the findings from human sequencing data.

Differences between humans and experimental models create a translational gap that makes it difficult to extrapolate research findings. The authors review systems-focused approaches to identify and control the translational distance between a complex disease process being studied and the experimental model used for testing.

In this Review, Isomura and Kageyama discuss how advances in live imaging, stem cell technologies and synthetic approaches are providing insights into the mechanisms underlying synchronization and species-specific periodicity of the mammalian segmentation clock during somitogenesis.

Intrinsically disordered domains (IDRs) are increasingly appreciated as important components of protein function. This Perspective discusses the emerging evidence for IDRs from transcription factors as contributors to the transcription factor target search process, as well as the challenges associated with studying these regions.

In this Review, Dowdle and Lykke-Andersen discuss advances in our understanding of the machinery and mechanisms involved in the control of cytoplasmic mRNA decay and comment on implications for the design of therapeutic mRNAs.

Collins and Talkowski provide a broad overview of structural variation in the human genome that covers their mutational properties, the dynamics of population genetics and functional consequences in disease as well as promising directions for future research.

Epigenetic clocks based on DNA methylation data are machine learning tools used to estimate chronological and biological age. The authors review computational and statistical challenges that must be addressed for the rigorous construction of interpretable epigenetic clocks at cell-type and single-cell resolution.

Circular RNAs have gained attention for their stability, immunological advantages and regulatory functions, making them a promising modality in multiple therapies. This Review discusses the therapeutic prospects of circular RNA-based approaches and the emerging role of circular RNAs as biomarkers in disease.

Recent genomic approaches are providing unprecedented opportunity to disentangle how genotype and environment affect organismal traits. The authors review the role of epigenetic variation in mediating the genotype–phenotype map across three scales: among individuals within a generation, across one or multiple generations, and long term over evolutionary time.

Controlling for phylogeny is essential in comparative genomics studies, because species, genomes and genes are not independent data points within statistical tests. The authors review the application of phylogeny-based comparative methods to genomic data to control for non-independence and how to test for causal hypotheses.

Loss of Y chromosome (LOY), the most commonly occurring post-zygotic (somatic) mutation in male individuals, affects immune activity and is associated with cancer, neurodegeneration, cardiovascular disease and infection. LOY is dynamic over time and has cell-type-specific effects, suggesting its potential as a biomarker and therapeutic target.

Studying germline variants and somatic mutations in cancer using omics technologies helps identify both heritable traits and molecular features of cancer genomes. Population-specific cancer genomics can reduce disparities and ensure equity across racial and ethnic groups for personalized medicine and public health approaches.

Kojima, Hoppe and Giraldez provide this cross-species Review of the cytoplasmic and nuclear remodelling that occurs after fertilization to permit zygotic genome activation (ZGA) and enable the shift from maternal to zygotic control of development (the maternal-to-zygotic transition).

Recent advances in genome engineering are enabling the recording of cellular histories into genomes, with single-cell and spatial omics technologies enabling their reconstruction into cellular lineages, states and exposures. This Perspective explores the rationale and technical basis of DNA recording, what aspects of cellular biology can be recorded and how, and the types of discovery that DNA recording will enable when studying development and disease.

Biobanks help centralize specimen collections, store and disseminate data, and facilitate large-scale analyses. This Review discusses how biobanks facilitate genetics research towards advancing precision medicine and overviews potential solutions to their current limitations.

Genomic and pangenomic data are yielding insights into the evolution of plant pattern recognition receptors (PRRs) and their molecular triggers. Recent advances in in silico and in vivo methods, alongside protein structure prediction, are helping to harness these insights for PRR engineering, offering sustainable solutions for broad-spectrum plant disease resistance.

In this Review, James et al. provide an overview of approaches for planning, constructing, and fine-tuning synthetic genomes and describe their potential applications.

Biomolecular condensates are membraneless cellular compartments that concentrate molecules such as proteins and nucleic acids. In this Review, the authors discuss how complementation experiments, a classic genetics approach, have provided valuable insights into the functions of biomolecular condensates.