Reviews & Analysis

This Review explores the use of non-mammalian model organisms in the genetic diagnosis of rare diseases, focusing on the use of worms, flies and zebrafish. The strategies, genetic technologies and approaches to using these models are discussed, as well as how they can provide insight into more common disease mechanisms.

Control can be applied to alter the ecological or evolutionary trajectory of a target system towards a predefined objective. In this Review, the authors discuss the aims, applications, mechanisms and dynamics of eco-evolutionary control across different biological systems.

In this Review, the authors summarize the current evidence for the use of genomic sequencing in newborn screening for rare diseases. As several large-scale studies launch internationally, the authors discuss major challenges and opportunities that lie ahead and identify key research priorities.

In this Review, the authors describe how the application of new technologies to the microRNA (miRNA) field has yielded key insights into miRNA biology. The authors summarize our current understanding of miRNA biogenesis, function and processing, and highlight challenges to address in future research.

Incongruence occurs when phylogenetic trees show conflicting evolutionary histories such as patterns of branching or relationships among taxa. This Review discusses the biological and analytical factors that lead to incongruence, methodological advances to identify and resolve incongruence, and avenues for future research.

Regulatory circuits of gene expression can be represented as gene regulatory networks (GRNs) that are useful to understand cellular identity and disease. Here, the authors review the computational methods used to infer GRNs — in particular from single-cell multi-omics data — as well as the biological insights that they can provide, and methods for their downstream analysis and experimental assessment.

This Review discusses the range of methods used for assessing the growth and fitness of SARS-CoV-2 variants, from classic population genetics to phylogenetics and epidemiological data, and describes future perspectives for surveillance of SARS-CoV-2.

This Review discusses how transposable elements contribute to mammalian genome evolution and gene regulation through their ability to both maintain and reshape 3D genome structure.

In this Perspective, Lim et al. discuss the potential benefits of, and the challenges associated with, translating single-cell genomic approaches from research to clinical settings.

The authors review genetic studies of sensorineural hearing impairment (SNHI) and their resulting insights into the molecular mechanisms underlying auditory system function. They also discuss preclinical studies of inner-ear gene therapy and key translational opportunities and challenges for treating monogenic forms of SNHI and associated balance disorders.

Recent systems biology and single-cell approaches have revealed the impact of the microenvironment, lineage specification and cell identity, and the genome on epithelial–mesenchymal plasticity (EMP). In addition, cell memory (hysteresis) and cellular noise can drive stochastic transitions between cell states. The authors review these forces and the regulatory mechanisms that stabilize EMP states or facilitate epithelial–mesenchymal transitions (EMTs).

Hook and Timp describe increasingly flexible ways in which single-molecule sequencing technologies are being used to analyse genomes. Examples include targeted genome sequencing, analysis of chromatin state and protein–DNA interactions, and sequencing of short reads.

In this Review, Gaulton et al. discuss how single-cell epigenomic methods generate cell type-, subtype- and state-resolved maps of candidate cis-regulatory elements in heterogeneous human tissues that can help to interpret the genetic basis of common traits and diseases.

Differences in facial morphology distinguish vertebrates. Here, Selleri and Rijli discuss advances in multi-omics and single-cell technologies linking genes, transcriptional networks and epigenetic landscapes to the establishment of facial patterning and its variation, with an emphasis on normal and abnormal craniofacial morphogenesis.

In this Review, the authors describe the emerging field of single-cell genetics, which lies at the intersection of single-cell genomics and human genetics. They review the first single-cell expression quantitative trait loci studies, which combine single-cell information with genotype data at the population scale and thereby link genetic variation to the cellular processes underpinning key aspects of human biology and disease.

Mutations that affect primary cilia cause ciliopathies with variable severity and expressivity. The diversity of cilia across cell types, tissues and developmental stages enables their function as versatile signalling hubs but may underlie the disconnect between genotype and phenotype. This Review examines the structural and functional diversity of primary cilia, their dynamic regulation in different cellular and developmental contexts and their disruption in disease.

Variant calling is the process of identifying genetic variants, which is important for characterizing population genetic diversity and for identifying disease-associated variants in clinical sequencing projects. In this Review, the authors discuss the state-of-the-art in variant calling, focusing on challenging types of genetic variants, advances in both sequencing technologies and computational pipelines, and benchmarking strategies to assess the robustness of variant-calling strategies.

In this Review, the authors discuss our growing knowledge of the underlying genetics of amyotrophic lateral sclerosis (ALS; also known as motor neuron disease). They discuss how this information provides insight into causal disease mechanisms and translational opportunities for developing clinical therapeutics.

Practitioners in the field of single-cell omics are now faced with diverse options for analytical tools to process and integrate data from various molecular modalities. In an Expert Recommendation article, the authors provide guidance on robust single-cell data analysis, including choices of best-performing tools from benchmarking studies.

In this Review, the authors discuss the latest advances in profiling multiple molecular modalities from single cells, including genomic, transcriptomic, epigenomic and proteomic information. They describe the diverse strategies for separately analysing different modalities, how the data can be computationally integrated, and approaches for obtaining spatially resolved data.