Software development for comprehensive variant detection would enhance our understanding of the human genome. Behera et al. introduce a method, dynamic read analysis for genomics (DRAGEN), to identify all types of genomic variant at scale and accuracy on Illumina’s whole-genome sequencing platform. The DRAGEN variant calling pipeline improves the accuracy of variant detection and enables more comprehensive

Aspects of single-cell RNA sequencing (scRNA-seq) data, such as its sparsity and high cell–cell variability, have made it hard to apply statistical approaches developed for bulk RNA-seq analyses, such as differential gene expression Kim et al. present Memento, a tool that uses methods-of-moments estimators of the hypergeometric sampling process to estimate single-cell gene abundances, variation and

Chondrocytes are cartilage cells that contribute to long-bone growth and are thus key to understanding height biology. However, our knowledge about epigenetic regulation and gene expression of human chondrocytes is sparse. To fill this gap, Richard et al. profiled chondrocytes sampled from different parts of the developing human skeleton (proximal and distal regions of limb bones) by RNA-seq and ATAC-seq

Spatiotemporal gene regulation is essential for accurate development and involves promoters and distal regulatory elements (DREs), such as enhancers or silencers. However, physical contacts with promoters do not always result in gene expression and how DREs contribute to gene activation is not fully understood. Mahara et al. combine chromatin conformation capture techniques with transcription and chromatin

Correction to: Nature Genetics https://doi.org/10.1038/s41588-024-01975-5, published online 21 November 2024.

Using reported parental disease history to decipher the genetics of Alzheimer’s disease may be promising, but this approach is also susceptible to complex selection and information bias that can mislead researchers if not accounted for.

A family tragedy revealed a hidden genetic mutation and transformed my work as a geneticist into a mission to increase awareness of the critical importance of genetic testing.

Correction to: Nature Genetics https://doi.org/10.1038/s41588-024-01958-6, published online 11 November 2024.

The standardized naming of gene variants in both databases and publications is crucial to ensure their discoverability and clinical application. Efforts are underway in conjunction with the Human Genome Organization (HUGO) to develop a field standard for variant reporting through the use of validation software prior to publication.

Pathogenic expansions of tandem repeat sequences underlie a diverse set of neurological conditions. To assess frequencies of repeat expansion mutations in the general population, Ibañez et al. analyzed whole-genome sequencing data from two large population-based studies comprising 82,176 individuals of diverse ancestries, focusing on 16 repeat expansion disorder loci for which they could accuracy classify

Dietary restriction and genetics can impact health and lifespan in various species. Di Francesco et al. investigated the effects of caloric restriction and intermittent fasting on the lifespan of 960 genetically diverse female mice, in which hundreds of physiological traits were profiled. These diverse outbred mice were randomized to one of five diet groups: ad libitum; 1 day or 2 consecutive days

Genome sequencing of large cohorts has identified many protein-coding missense variants, the functional consequences of which remain difficult to predict computationally. Lacoste et al. use a new high-throughput screening approach to characterize the effects of known pathogenic variants on protein localization. They analyzed a total of 3,448 variants, many with known or likely pathogenicity in the

Previous studies have characterized chromatin conformation and DNA methylation dynamics in early postnatal and adult brain tissues. To gain single-cell resolution, Heffel et al. used single-nucleus methyl-3C sequencing to profile chromatin conformation and DNA methylation during human prenatal development of the prefrontal cortex and hippocampus and compared these with postnatal and adult tissues.

Optical pooled CRISPR screens have been widely adopted for functional genomic studies. Gu et al. present CRISPRmap, an optical pooled screening approach that integrates sequencing-free in situ barcode readout with cyclic immunofluorescence and RNA detection. The cyclical hybridization readout method improves the specificity and sensitivity of barcode detection through combinatorial hybridization of

Mammalian pachytene PIWI-interacting RNAs (piRNAs) are expressed during the pachytene stage in spermatocytes with proposed roles in the regulation of meiosis. However, their specific functions and targets remain elusive. In this study, Swathi Arur and colleagues interrogate the function of 21URNAs, the Caenorhabditis elegans piRNAs, and the PIWI homolog prg-1 in the male germline. They show that loss

The combination of different checkpoint inhibitors has been shown to benefit some patients with non-small cell lung cancer (NSCLC), but identifying those who are most likely to benefit and sparing patients who will not remains a crucial challenge. Skoulidis et al. show that tumors with mutations in KEAP1 and/or STK11 are more likely to respond to dual PD-L1 and CTLA4 blockade (with the inhibitors durvalumab

Correction to: Nature Genetics https://doi.org/10.1038/s41588-024-01921-5. Published online 15 October 2024.

Correction to: Nature Genetics https://doi.org/10.1038/s41588-024-01938-w, published online 2 October 2024.