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Anti-cancer fluoropyrimidine drugs have antibacterial effects on the gut microbiome, and these drugs can be metabolized by gut bacteria via conserved pathways also found in mammalian hosts.

Determinants of Vibrio cholerae transmission are incompletely understood. Here, the authors use an infant mouse model to show that events in the intestine govern inter-animal transmission and that bacterial motility along with cholera toxin-driven diarrhea are critical for pathogen spread.

Single molecule kinetics investigations and molecular simulations are useful tools in elucidating protein assembly mechanisms. Here, the authors use these to show that even naturally occurring tandem repeats undergo transient misfolding and that assembly is much more complex than we previously understood.

Gastrointestinal distress is common among individuals with autism. Here, authors show that autism gene variants disrupt enteric neuron migration and cause gut dysmotility. They identify a common SSRI that can ameliorate this dysmotility in Xenopus.

Isolating and studying haematopoietic stem cells in young and aged mice demonstrates evolutionary processes related to blood production and provides a framework for interpreting future work using laboratory mice to study stem cell ageing.

Glucocorticoid resistance is partly due to epigenetic alterations, but the regulatory mechanisms driving these remain poorly understood. Here, a link between the activity of a lineage-specific transcription factor PU.1 and epigenetic modulators mediating the response to glucocorticoids is described in acute lymphoblastic leukemia.

Marra and colleagues describe POG570, a pan-cancer, whole-genome, transcriptome and clinical dataset stressing the molecular interactions in advanced and post-therapy cancer patients.

The mechanisms of tumor heterogeneity in pediatric hepatoblastoma remain poorly characterized. Here, the authors perform single cell RNA sequencing and identify 5 signatures with distinct responses to chemotherapy using patient-derived hepatoblastoma spheroid cultures.

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.

Nabbi et. al. analyze immunohistochemistry, comprehensive genomic profiling, RNA-sequencing, and TCR-sequencing data from 66 pediatric patients with cancer from a phase 1–2 clinical trial (iMATRIX-atezo) to nominate biomarkers associated with response to immunotherapy in pediatric cancer.

Cancer biomarkers are often continuous measurements, which poses challenges for their prediction using classification-based deep learning. Here, the authors develop a regression-based deep learning method to predict continuous biomarkers - such as the homologous repair deficiency score - from cancer histopathology images.

Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.

Using data from a single time point, passenger-approximated clonal expansion rate (PACER) estimates the fitness of common driver mutations that lead to clonal haematopoiesis and identifies TCL1A activation as a mediator of clonal expansion.

It has been previously shown that combining immune checkpoint inhibitors with TGFβ blockade potentiates anti-tumor immune responses. Here the authors show that, in an immune excluded preclinical tumor model, combining therapeutic anti-PD-L1 with anti-TGFβ treatment promotes expansion and differentiation of stem-cell like CD8 + T cells.

The non-coding RNA RNU4-2, which is highly expressed in the developing human brain, is identified as a syndromic neurodevelopmental disorder gene, and, using RNA sequencing, 5′ splice-site use is shown to be systematically disrupted in individuals with RNU4-2 variants.

A large-scale meta-analysis across eight biobank datasets identifies common genetic variants associated with mosaic loss of the X chromosome in female participants.

High-performance cathode materials are crucial for the development of solid oxide fuel cells. Here, the authors present a nanoengineering approach to boost cathode performance in conventional anode-supported cells, demonstrating a viable route to attaining higher power output.

A sequencing chemistry that separates nucleotide identification from nucleotide incorporation achieves high accuracy.

Fine-mapping of causal variants and integration of epigenetic and chromatin conformation data identify likely target genes for 150 breast cancer risk regions.

Chassis-independent recombinase-assisted genome engineering (CRAGE) enables the integration of plasmids encoding biosynthetic gene clusters into the chromosomes of diverse bacteria to optimize production of natural products in non-native strains.

The genetic basis of atopic dermatitis is not fully understood. Here, the authors find 91 genetic loci associated with atopic dermatitis in a GWAS of >1million individuals, which highlight the importance of systemic immune regulation.

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.

The Somatic Mosaicism across Human Tissues Network aims to create a reference catalogue of somatic mosaicism across different tissues and cells within individuals.

The warm Earth-sized planet LHS 475 b is validated and characterized with two transits observed by the JWST. The absence of evident spectroscopic features excludes a substantial hydrogen envelope and indicates that LHS 475 b has either little or no atmosphere or an optically thick cloud deck at high altitudes.

The results obtained by seventy different teams analysing the same functional magnetic resonance imaging dataset show substantial variation, highlighting the influence of analytical choices and the importance of sharing workflows publicly and performing multiple analyses.

A genomic constraint map for the human genome constructed using data from 76,156 human genomes from the Genome Aggregation Database shows that non-coding constrained regions are enriched for regulatory elements and variants associated with complex diseases and traits.

Short-read sequencing has inherent limitations in the characterisation of long repeat elements. Shi and Guo et al.combine single-molecule real-time sequencing and IrysChip to construct a Chinese reference genome that fills many gaps in the reference genome, and identify novel spliced genes.

The impact of cisplatin-based chemotherapy on tumor genomes is complex. Here, the authors study matched pre- and post-chemotherapy primary samples in muscle-invasive bladder cancer, finding a cisplatin-based mutational signature, and highlighting the impact of intratumor heterogeneity on survival.

The DNA helicase ASCC3 is the largest subunit of the activating signal co-integrator complex (ASCC), and its DNA unwinding activity is required for the AlkBH3/ASCC-dependent DNA de-alkylation repair pathway. Here, the authors identify a minimal stable complex of the two ASCC subunits ASCC2 and ASCC3, determine the complex crystal structure and further show that cancer-related mutations at the interface between both proteins reduce ASCC2–ASCC3 affinity.

Understanding the mechanisms causing cardiac fibrosis is key to prevention and therapy development of many heart diseases. Here, the authors show that Wnt/β-catenin signaling in resident cardiac fibroblasts is required for deposition of fibrotic extracellular matrix and the regulation of cardiomyocyte hypertrophy in a mouse model of heart fibrosis.

Oncolytic viruses can activate tumor neoantigen-specific T cell responses. However, PD-L1 upregulation on tumor cells and immune cells leads to tumor resistance to this immunotherapy approach. Here, the authors develop an oncolytic virus which expresses both a PD-L1 inhibitor and GM-CSF which allows an improved tumor neoantigen-specific T cell response in preclinical models.

ASCC3 is a multi-functional helicase that contains two consecutive Ski2-like helicase units. Here, the authors show that ASCC3 can unwind DNA by threading one strand of a substrate duplex through both helicase units, supported by the TRIP4 protein.

Viral infection of the respiratory system induces exuberant fibroblast activity, resulting in extensive remodelling of the extracellular matrix and cytokine release, which promote immune cell infiltration of the affected area at the expense of respiratory function.

The Impact of Genomic Variation on Function Consortium is combining single-cell mapping, genomic perturbations and predictive modelling to investigate relationships between human genomic variation, genome function and phenotypes and will provide an open resource to the community.

Meeting emissions targets requires limiting use of fossil fuel reserves. For the largest investor- and state-owned producers allowable extraction varies dependent on the approach to calculate burnable fossil fuel allowance.

This paper shows that specific genetic disruption of the Ncor–HdaC3 interaction in mice causes aberrant regulation of clock genes and results in abnormal circadian behaviour. These mice are also leaner and more insulin sensitive due to increased energy expenditure. Loss of a functional Ncor–HdaC3 complex in vivo changes the oscillatory patterns of several metabolic genes, demonstrating that circadian regulation of metabolism is critical for normal energy balance.