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This paper presents TDAC-seq, a targeted chromatin-accessibility-profiling method using cytidine deaminases and long-read sequencing, to resolve the effects of CRISPR edits on single chromatin fibers.

Pathogen diagnostics are strong determinants of azithromycin effects on diarrhea duration, but host factors may better predict benefits for severe outcomes. In this work, authors utilise a machine learning-based approach to evaluate personalized rules for the decision to treat watery diarrhea with azithromycin.

Transcription creates superhelical stress in DNA, challenging genome stability. Here the authors find Top2 activity is uncorrelated with transcription unless chromatin is disrupted suggesting that chromatin buffers latent topological stress.

A phase I trial of a neoantigen-targeting personalized cancer vaccine led to durable and polyfunctional T cell responses and antitumour recognition, and was associated with no recurrence in patients with high-risk clear cell renal cell carcinoma.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

The major ion chemistry of a North American river shows decreased lateral carbon transport due to exacerbated secondary carbonate formation and CO₂ evasion, according to analyses conducted during a 195-day drought.

To date, experimental induction of hair cell regeneration in mammals leads to immature and poorly differentiated hair cells. Here the authors show that the transcription factor prdm1a plays a crucial role in specifying sensory hair cell types with loss of prdm1a in zebrafish leading to misspecification of hair cells in the sensory lateral line system into ear hair cells.

In this study, Weber et al., investigate the long-term survival and integration of human stem cell-derived neural progenitors into the stroke-injured mouse brains. They report grafted cells integrate into host circuits and mediate repair through graft-host crosstalk via neurexin, neuregulin, neural cell adhesion molecules, and SLIT signalling pathways.

An international conference about gentrification gathered scholars, activists and practitioners to discuss urban changes worldwide that are displacing poorer residents to develop upscale areas.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

An Atlantic meridional overturning circulation slowdown drives widespread shifts in tropical rainfall through the propagation of high-latitude cooling into the tropical North Atlantic.

A design pipeline is presented whereby binding proteins can be designed de novo without the need for prior information on binding hotspots or fragments from structures of complexes with binding partners.

The scarcity of targetable proteins broadly expressed on cancer cells, but not on healthy cells, is an obstacle for chimeric antigen receptor (CAR)-T cell therapy. Here the authors establish that a functionally impaired version of P2X purinoceptor 7, non-functional P2X7 (nfP2X7), fulfils these criteria, and demonstrate that CAR-T cells targeting nfP2X7 efficiently and selectively kill breast and prostate cancer cells in mouse models.

A novel antiviral targeting the SARS-CoV-2 PLpro protease shows strong efficacy in a mouse model, preventing lung pathology and reducing brain dysfunction. The study provides proof-of-principle that PLpro inhibition may be a viable strategy for preventing and treating long COVID.

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.

Networks of miniaturized magnetoelectric wireless implantable devices can be individually powered and controlled by a single transmitter, show power and transfer data efficiencies that scale with the number of receivers and be used for spinal cord stimulation and cardiac pacing in large animals.

By introducing chiroptical spectroscopy with attosecond pulses, attosecond coherent control over photoelectron circular dichroism is demonstrated and measurements of chiral asymmetries in the forward–backward and angle-resolved photoionization delays of chiral molecules are reported.

The analysis of pairs of identical SARS-CoV-2 genome sequences enables characterization of transmission patterns between geographies and age groups.

Filamin C is a key actin-binding protein involved in cardiomyopathies and musculoskeletal disorders. Here, Wang et al reveal that it interacts with the heat shock protein HSPB7 under biomechanical stress, forming a stable hetero-dimer which is regulated by phosphorylation.

ATLAS is a tool for circuit tracing, demonstrated here in rodents. It allows anterograde transsynaptic tracing, starting from genetically defined neurons.

Yuan et al. present S2-omics, an end-to-end workflow that automatically identifies regions of interest in histology images to maximize molecular information capture in spatial omics experiments.

The authors reveal that the chromatin architectural proteins CTCF and RAD21 organize DNA around nuclear speckles to enhance gene induction. This structural organization, when disrupted as in Cornelia de Lange syndrome, impairs key gene functions, providing insight into potential disease mechanisms.

Here the authors conduct a multi-ancestry meta-analysis of telomere length, used diverse approaches to identify genes underlying association signals, and experimentally validated POP5 and KBTBD6 as regulators of telomere length in human cells.

Genome-wide association meta-analyses of attention-deficit/hyperactivity disorder symptom measures and clinical diagnoses identify new risk loci, highlight putative effector genes and yield improved polygenic risk scores.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Extreme-ultraviolet frequency combs have previously been used to realize spectroscopy with a megahertz level resolution, but higher resolutions are desired for precision-measurement applications. Now, a sub-hertz spectral resolution is demonstrated, which corresponds to coherence times of over 1 s at photon energies up to 20 eV; such coherence times are over six orders of magnitude longer than those previously reported.

Phylogeographic analysis of 792 Ebola virus genomes from the 2018 oubreak in the Democratic Republic of the Congo integrated into an end-to-end surveillance program demonstrates the feasibility of using genomic sequencing data to inform the public health epidemic response in near-real time.

Analysis of metagenomes from across the globe reveals the spectrum of soil microbial functional diversity based on community aggregated traits.

This meta-analysis assesses the rates and drivers of greenhouse gas emissions from flowing and standing (sub)tropical inland waters, finding that emissions are lower than previous estimates. Considerable spatial variation in fluxes arises mainly from differences in hydroclimate, geomorphology, land cover and human disturbance.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

Perineural invasion and cancer-induced nerve injury of tumour-associated nerves are associated with poor response to anti-PD-1 therapy, which can be reversed by combining anti-PD-1 therapy with anti-inflammatory interventions.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Smale and colleagues explore evolutionary divergence in the NF-κB family. They show that intrinsic DNA-binding affinity rather than specificity led to neofunctionalization in mammals within this transcription factor family, supporting immunoregulatory rewiring in mammalian species.

Analysis of whole-genome sequences of 25,465 individuals of European ancestry shows that rare variants contribute substantially to the heritability of height and body mass index.

Topoisomerase 2 (Top2) is known to resolve DNA topological stress through double strand breaks (DSBs), yet Top2 inhibition has been reported to result in a significant amount of single-strand breaks (SSBs). Here the authors develop CC-seq—a method that allows direct mapping of both Top2-linked SSBs and DSBs—and reveal a significant impact of primary DNA sequence on Top2 directed cleavage.

RNA-sequencing analysis of cells in the human cortex enabled identification of diverse cell types, revealing well-conserved architecture and homologous cell types as well as extensive differences when compared with datasets covering the analogous region of the mouse brain.

Exome sequencing of 851 trios from more than 2,500 individuals finds 187 genes with de novo mutations that contribute to meningomyelocele (spina bifida) and highlights critical pathways required for neural tube closure.

Single-nucleus and single-cell RNA sequencing plus spatial profiling with four methods of core biopsies from 60 patients with metastatic breast cancer reveal patient-specific gene expression programs of breast cancer metastases that are maintained across time, site of metastasis and spatial profiling method, with spatial phenotypes correlating with microenvironmental features.

Spatially resolved transcriptomic profiling of primary tumours and metastases from patients with pancreatic cancer provides insight into the evolutionary progression to metastasis, and the variation in clonal architecture within and between individuals.

Multi-ancestry genome-wide association meta-analysis of major depression identifies new risk loci, assesses the transferability of risk loci across ancestry groups, and improves fine-mapping resolution and prioritization of candidate effector genes.

No preventive treatment addresses the underlying condition that leads to cardiac arrest. Here, researchers developed an injectable hydrogel electrode that achieves pacing that mimics physiological conduction with the potential to eliminate lethal arrhythmias and provide painless defibrillation.

Here the authors developed ‘Lamina-Inducible Methylation and Hi-C’ (LIMe-Hi-C) to simultaneously measure chromosome conformation, DNA methylation, and nuclear lamina positioning. Application of the method revealed dynamic changes upon PRC2 inhibition and an essential function of H3K27me3 in regulating sub-compartments and lamina association.

Gain of function mutant CaV1.2 channels drive life-threatening hypoglycemia in the multisystem disorder Timothy syndrome, but the underlying mechanisms are unknown. Here the authors show the mutant channels have adverse effects on counterregulatory hormones and CNS control of glucose homeostasis.

Raman and fluorescence spectra, consistent with several species of aromatic organic molecules, are reported in the Crater Floor sequences of Jezero crater, Mars, suggesting multiple mechanisms of organic synthesis, transport, or preservation.

Stereotactic needle biopsies are currently performed for diagnosis only in glioblastoma; this study highlights the depth of information available through multi-omics analysis.

Studying socioeconomic backgrounds and intergenerational transmission in the US academia, Morgan et al. find that faculty have a parent with a Ph.D. degree a striking 25 times more often than the general population.

Engineered polyketide synthases (PKSs) have great potential as biocatalysts for the synthesis of chemically challenging molecules. Here the authors show a retrobiosynthesis approach to design and construct PKSs to produce a series of valerolactams for biopolymer production.