Reviews & Analysis

In this Review, Li and Durbin discuss how to generate telomere-to-telomere assemblies for large haploid or diploid genomes using currently available data types and algorithms, and outline remaining challenges in resolving highly repetitive sequences and polyploid genomes.

In this Review, the authors summarize our current understanding of nuclear pre-mRNA and mRNA decay pathways. They describe how aberrantly processed mRNAs are targeted for decay in the nucleus and how this process is regulated to finely control gene expression.

In this Perspective, Werner and colleagues discuss the many potential mechanisms by which natural antisense transcripts (NATs) can regulate expression of their complementary sense transcripts, the biological implications of their regulatory effects and the potential of NATs for therapeutic applications.

Genetic variants acquired early during embryogenesis can affect numerous tissues. The authors review the phenomenon of embryonic mosaicism, with a focus on small variants, and discuss mechanisms of cell competition that allow mosaic clones to expand, as well as the functional consequences of mosaicism for embryo viability and the health of the organism.

In this Review, Mackay and Anholt discuss how epistasis and pleiotropy contribute to the genetic architecture of quantitative traits and outline factors that might explain observed differences in their prevalence between model organisms and humans.

In this Review, the authors compare the characteristics and detection methods of germline and somatic variants. Furthermore, they outline how the interplay between the two types of genetic variation can affect human health.

Plants have uniquely adapted to manage endoplasmic reticulum stress triggered by protein misfolding. The authors review the dynamics of gene expression regulation underlying the unfolded protein response in plants, highlighting recent insights provided by systems-level approaches and omics data.

This Review highlights the diversity in sequence composition of disease-related short tandem repeats. The authors discuss how to detect non-canonical motifs in repeat sequences from sequencing data and review the molecular and clinical consequences of sequence composition changes.

In this Review, Sayers et al. summarize findings from recent large-scale genetic epidemiology studies on the genetic underpinnings of chronic respiratory diseases. Furthermore, they outline how insights gained from such studies can improve treatment approaches.

Therapeutics that target long non-coding RNAs (lncRNAs) are promising treatments for cancer. In this Review, the authors discuss how technological advances have helped improve drug discovery pipelines for lncRNAs and overview their strengths and challenges as oncological therapeutics.

Plant pangenomes have had a transformative impact on crop enhancement, biodiversity conservation and evolutionary research. This Review delves into the application of plant pangenomes for understanding trait diversity, aiding breeding, biodiversity classification and monitoring, and illuminating evolutionary innovations.

This Review discusses the evolutionary origin of Wnt signalling, its ancestral function and the characteristics of the primal Wnt ligand. It emphasizes the importance of genomic studies in pre-metazoan and basal metazoan species to understanding the evolutionary origin of signalling pathways.

This Review describes tools and approaches for characterizing short tandem repeats in the human genome from whole-genome sequencing data. Furthermore, the authors discuss how these recent developments have helped to better understand the effect of short tandem repeats on human health and disease.

Multiple mechanisms have evolved to prevent or trap deleterious unwanted transcripts. The unwanted transcript hypothesis proposes that selection at synonymous sites favours mutations that prevent the generation of unwanted transcripts or that make native transcripts appear ‘wanted’ by being GC-rich.

To successfully invade bacteria, bacteriophages and other mobile genetic elements must overcome numerous types of bacterial defence systems. Here, the authors review the discovery and mechanisms of direct inhibitors of bacterial defence systems, as well as their applications in biotechnology.

In this Review, Patrick Keeling proposes that the eukaryotic-specific processes of phagocytosis and endosymbiosis are unlikely to increase the frequency of horizontal gene transfers, because most of the transferred genes will be non-essential and will thus not be selected for the long term.

In this Review, the authors summarize recent progress in cell–cell interaction (CCI) research. They describe the recent evolution in computational tools that underpin CCI studies, discuss improvements in experimental methods enabling more high-throughput analyses of CCIs, and highlight future directions for the field.

Genomic technologies have greatly improved the diagnosis of rare genetic diseases. Here, the authors review emerging approaches for the identification of disease-causal genetic variants as well as omic technologies that show great potential for variant interpretation.

In this Review, the authors summarize and discuss guidelines for omics benchmarking. They highlight common oversights and difficulties, offer guidance for frequently encountered issues and provide a structured form that can be used for comprehensive reporting of benchmarking studies.

In this Review, Hwang and co-authors outline single-molecule fluorescence imaging techniques that can be used in living cells to visualize individual molecules involved in the spatiotemporal regulation of gene expression. This Review also delves into the biological insights gained through these methodologies.