Reviews & Analysis

Commemorating the 200th birthday of Gregor Mendel, Kim Nasmyth reflects on Mendel’s life and legacy and how his work has shaped and defined the field of modern genetics.

Publicly available sequencing data can be used as external common controls for rare variant analyses but cautious sample ascertainment and processing is needed to avoid bias and confounding. The authors review opportunities and challenges for the robust use of common controls in genetic studies, including study design, infrastructure and quality control considerations.

In this Review, the authors give an overview of age-related changes to the methylation landscape and the statistical tools used to quantify them. They also discuss the evidence for longevity strategies that aim to counter these changes, and the candidate mechanistic causes of epigenetic ageing.

In this article, Niemi, Daly and Ganna discuss how large-scale genomics studies are providing a rapidly maturing understanding of the influence of host genetics on coronavirus disease 2019 (COVID-19) susceptibility and severity. They also describe the implications for identifying causal mechanisms of pathology and potential therapeutic opportunities.

Rackham and Filipovska review our current understanding of mitochondrial genome organization and expression, and discuss how new technologies and animal models are providing insights into how its mis-regulation leads to diseases of impaired energy conversion.

In this Review, the authors describe how phylogenetic and phylodynamic methods provide insight into viral evolution, focusing on the SARS-CoV-2 pandemic. The approaches reveal routes and timings of transmission events, and they can assess the effectiveness of various intervention measures aimed at controlling the virus.

In this Viewpoint, we asked six experts to give their opinions on the utility of polygenic scores, their strengths and limitations, and the remaining barriers that need to be overcome for their equitable use.

Histone post-translational modifications (PTMs) have been mainly regarded as instructing DNA-templated processes. In this Review, Gonzalo Millán-Zambrano and colleagues describe how histone PTMs both affect and are affected by these DNA processes and should be viewed as components of a complex genome-regulating network.

This Review discusses the types of single and multiple human organ-on-a-chip (organ chip) microfluidic devices and their diverse applications for disease modelling, drug development and personalized medicine, as well as the challenges that must be overcome for organ chips to reach their full potential.

DNA methylation-based predictors of health aim to predict outcomes such as exposure, phenotype or disease on the basis of genome-wide levels of DNA methylation. The authors review applications of existing DNA methylation-based predictors and highlight key statistical best practices to ensure their reliable performance.

In this Review, Boulias and Greer provide an overview of current approaches for detecting and mapping N⁶-methyl-2′-deoxyadenosine (6mA or m⁶dA), and discuss the evidence for its presence and functional importance in the genomes of multicellular eukaryotes.

In this Perspective, Pecori et al. provide an overview of the AID/APOBEC cytidine deaminase family, discussing key structural features, how they contribute to viral and tumour evolution and how they can be harnessed for (potentially therapeutic) base-editing purposes.

In this Review, the authors describe technical and legal protection mechanisms for mitigating vulnerabilities in genomic data privacy. They also discuss how these protections are dependent on the context of data use such as in research, health care, direct-to-consumer testing or forensic investigations.

Single-cell transcriptomics is beginning to systematically define commonalities but also heterogeneity within and between organs for multiple human cell types. Here, the authors review emerging biological insights from cross-tissue single-cell transcriptomic studies into epithelial, fibroblast, vascular and immune cells.

The reduction in individual and mean population fitness induced by novel deleterious genetic variation is known as the genetic load. Bertorelle et al. review the definition of the genetic load and its components as well as the impact of whole-genome sequencing on the theoretical and applied study of the genetic load.

In this Review, Ding, Sharon and Bar-Joseph discuss how dynamic features can be incorporated into single-cell transcriptomics studies, using both experimental and computational strategies to provide biological insights.

Cell fusion models containing genomes from different cell types or species in a single nucleus offer unique research benefits. Here, Pavlovic et al. advocate against describing such models as hybrids and propose a new nomenclature for interspecies cell fusions that lacks reproductive connotations.

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.

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.