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CRISPRi-based screen identifies enhancers that nonlinearly regulate lineage-specifying transcription factors during definitive endoderm differentiation. A new CTCF-loop-constrained Interaction Activity (CIA) model is better at predicting functional enhancers than previous Hi-C-based enhancer–promoter contact frequency models.

The ability of HIV to alternate between acute and latent forms is thought to rely on a transcriptional feedback loop where polymerase pausing is released by the viral protein Tat. Here, the authors show that viral genome transcription can occur in a burst-like stochastic manner in the absence of Tat.

Cooperative species of extrachromosomal DNAs are coordinately inherited through mitotic co-segregation.

The BioDIGS project is a nationwide initiative involving students, researchers and educators across more than 40 research and teaching institutions. Participants lead sample collection, computational analysis and results interpretation to understand the relationships between the soil microbiome, environment and health.

Here, Rathnasinghe et al. characterize the pathogenesis of a mouse-adapted SARS-CoV-2 in infected obese and aged mice, and identify mutations that are present in SARS-CoV-2 variants of concern, associated with higher transmissibility.

Fire-derived organic matter (OM) is present throughout the environment, and its impact on nutrient cycling remains poorly understood. Here, the authors show that this pyrogenic OM can retain large quantities of ammonia through covalent bond formation, thereby exerting an important control on nitrogen cycling.

A study of several longitudinal birth cohorts and cross-sectional cohorts finds only moderate overlap in genetic variants between autism that is diagnosed earlier and that diagnosed later, so they may represent aetiologically different conditions.

Multi-ancestry genome-wide analyses identify 95 loci associated with post-traumatic stress disorder and implicate candidate genes, pathways and neurobiological systems underlying its pathophysiology.

Field studies of the bat-to-bat transfer and ingestion of fluorescent biomarkers as a proxy for an oral vaccine are combined with mathematical models to predict the efficacy of oral vaccines for reducing bat rabies outbreaks.

A combination of computational modelling and empirical data is used to explore the network structure of infection and immunity in CRISPR–Cas host–virus interactions.

A multi-ancestry genome-wide association study of problematic alcohol use in one million individuals identified 110 risk variants and shows that multi-ancestry polygenic scores improve risk prediction compared with single-ancestry scores

Analysis of whole-genome doubling (WGD) by using cancer sequencing data combined with simulations of tumor evolution suggests that there is negative selection against homozygous loss of essential genes before WGD but not after.

Post-traumatic stress disorder (PTSD) is a common mental health problem. Here, the authors report a GWAS from the Psychiatric Genomics Consortium in which they identify two risk loci in European ancestry and one locus in African ancestry individuals and find that PTSD is genetically correlated with several other psychiatric traits.

Study shows PTSD predisposition shares distinct genes and genomic regions with several cardiovascular conditions. Here the findings reveal neuronal, immune, and metabolic pathways, and repurposed drug targets that further the understanding of the comorbidity.

Cortex morphology varies with age, cognitive function, and in neurological and psychiatric diseases. Here the authors report 160 genome-wide significant associations with thickness, surface area and volume of the total cortex and 34 cortical regions from a GWAS meta-analysis in 22,824 adults.

The authors summarize the data produced by phase III of the Encyclopedia of DNA Elements (ENCODE) project, a resource for better understanding of the human and mouse genomes.

This overview of the ENCODE project outlines the data accumulated so far, revealing that 80% of the human genome now has at least one biochemical function assigned to it; the newly identified functional elements should aid the interpretation of results of genome-wide association studies, as many correspond to sites of association with human disease.

Here the authors deliver aerosolized human monoclonal antibodies to SARS-CoV-2-infected rhesus macaques and show that the treatment significantly reduces viral RNA and infectious virus in the respiratory tracts, limits lung pathology, and decreases inflammatory cytokines.

In this study, Vande Voorde et al. investigate the potential of untargeted metabolomics as a stratification tool for colorectal cancer (CRC). They present a comprehensive pipeline to uncover metabolic vulnerabilities in CRC based on its genetic origin. With this approach, they show perturbations in methionine metabolism linked to APC deficiency, and identify adenosylhomocysteinase as an actionable therapeutic target.

The BRAIN Initiative Cell Census Network has constructed a multimodal cell census and atlas of the mammalian primary motor cortex in a landmark effort towards understanding brain cell-type diversity, neural circuit organization and brain function.

The predicted rise in CO₂ levels during this century is expected to stimulate crop yields, offsetting losses from greater drought. But this study, using free-air CO₂ enrichment, shows soybean yield gains dropping to zero as drought stress increased.

The authors summarize the history of the ENCODE Project, the achievements of ENCODE 1 and ENCODE 2, and how the new data generated and analysed in ENCODE 3 complement the previous phases.

The US National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institute of Health (NIH), convened a virtual workshop on August 8-9^th, 2023 to explore potential synergies between HIV vaccine approaches that are designed to induce cellular or humoral immune responses. The goal of this workshop was to review data on leading vaccine candidates and to discuss the best strategies for combining these approaches to optimize immunity against HIV. Here, we summarize the findings reviewed at the workshop and discuss the knowledge gaps and priorities for future studies that will help accelerate the development of a preventive HIV vaccine.

Mutations in the gene encoding DNA methyltransferase 3A (DNMT3A) have been reported in patients with various haematological malignancies, suggesting that DNMT3A could be a tumour suppressor. In this Review, Yanget al. put data from basic science studies into clinical context, opening stimulating discussions regarding possible new therapeutic avenues.