Nature Reviews Genetics, Published online: 10 October 2025; doi:10.1038/s41576-025-00900-8This article reviews the current state of implementation of polygenic risk scores in the clinical setting, highlights key challenges and outlines future directions for the use of such scores to improve disease risk prediction and to enable personalized prevention.

Nature Reviews Genetics, Published online: 25 April 2025; doi:10.1038/s41576-025-00832-3In this Review, Shao et al. discuss experimental and computational advances in single-cell DNA sequencing, insights into somatic genetic variation during normal development and in disease, and the potential use of single-cell somatic mutations for lineage tracing, diagnostics and biomarkers.

Spatial omics has empowered the discovery of developmental and disease-associated molecular signatures, cell states and multicellular niches, as well as the evaluation of disease heterogeneity within and across organs. The authors review spatially resolved molecular changes across diseases and discuss the potential of spatial multi-omics for clinical applications, including the recent impact of artificial intelligence.

Nature Reviews Genetics, Published online: 08 October 2025; doi:10.1038/s41576-025-00896-1Recent advances in forensic genetics have improved the range, precision and reliability of forensic information obtainable from biological trace material. The author reviews how non-targeted and targeted omics approaches and methods are improving crime scene analyses being applied for the identification of perpetrators and their relatives or victims, the prediction of phenotypic traits, and the determination of trace characteristics.

Nature Reviews Genetics, Published online: 01 October 2025; doi:10.1038/s41576-025-00901-7Sara Suliman describes a seminal 2013 publication by Comas et al. that investigated the origins of the tuberculosis-causing bacteria and its coevolution with diverse human populations.

Nature Reviews Genetics, Published online: 16 September 2025; doi:10.1038/s41576-025-00880-9In this Comment, Wendy Bickmore discusses mechanistic models of how 3D genome organization facilitates communication between distant enhancers and their target promoters to regulate gene expression.

Nature Reviews Genetics, Published online: 16 September 2025; doi:10.1038/s41576-025-00885-4After more than two decades of large-scale efforts to annotate the regulatory genome, Sushant Kumar and Mark Gerstein forecast how new technologies and experimental approaches will pave the way in mapping regulatory elements across cell types, developmental stages and genetically diverse individuals.

Nature Reviews Genetics, Published online: 16 September 2025; doi:10.1038/s41576-025-00882-7In this Comment, the authors outline some key next steps to advance our understanding of cis-regulatory elements at single-cell resolution, which includes harmonizing global efforts to construct a comprehensive single-cell atlas of gene regulation.

Nature Reviews Genetics, Published online: 16 September 2025; doi:10.1038/s41576-025-00894-3For the 25th anniversary of Nature Reviews Genetics, we reflect on exciting progress towards decoding the regulatory genome and its mechanisms, a central goal in genetics that must be solved with interdisciplinary research to yield widespread insights into evolution, development and disease.

Nature Reviews Genetics, Published online: 16 September 2025; doi:10.1038/s41576-025-00879-2Studies of human regulatory genomics are being performed at biobank scales, with data from tens of thousands of individuals. Stephen Montgomery describes how these datasets will advance our understanding of how variation in gene regulation shapes human traits and disease.

Nature Reviews Genetics, Published online: 30 September 2025; doi:10.1038/s41576-025-00892-5Spatial omics has empowered the discovery of developmental and disease-associated molecular signatures, cell states and multicellular niches, as well as the evaluation of disease heterogeneity within and across organs. The authors review spatially resolved molecular changes across diseases and discuss the potential of spatial multi-omics for clinical applications, including the recent impact of artificial intelligence.

Nature Reviews Genetics, Published online: 07 October 2025; doi:10.1038/s41576-025-00902-6In this Journal Club, Tzachi Hagai highlights a 2005 paper by Sawyer et al. that tested the functional relationship of evolutionary changes in immune genes with infection outcomes.

Nature Reviews Genetics, Published online: 15 September 2025; doi:10.1038/s41576-025-00888-1Genome-wide approaches have uncovered the vast microbial and viral diversity across ecosystems. This Review explores advances in metagenomics, single-cell sequencing and functional profiling to elucidate the evolution, biogeography and ecological dynamics of Earth’s microbiomes.

Nature Reviews Genetics, Published online: 26 September 2025; doi:10.1038/s41576-025-00898-zGerald Mboowa reflects on the dual legacy of a 2021 study by Frangoul et al., which demonstrated safe and effective CRISPR-based editing to treat sickle-cell disease and β-thalassemia, as both a triumph of modern science and a call to action for global health.

Nature Reviews Genetics, Published online: 30 September 2025; doi:10.1038/s41576-025-00892-5Spatial omics has empowered the discovery of developmental and disease-associated molecular signatures, cell states and multicellular niches, as well as the evaluation of disease heterogeneity within and across organs. The authors review spatially resolved molecular changes across diseases and discuss the potential of spatial multi-omics for clinical applications, including the recent impact of artificial intelligence.