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Results for the final phase of the 1000 Genomes Project are presented including whole-genome sequencing, targeted exome sequencing, and genotyping on high-density SNP arrays for 2,504 individuals across 26 populations, providing a global reference data set to support biomedical genetics.

A region on chromosome 19p13 is associated with the risk of developing ovarian and breast cancer. Here, the authors genotyped SNPs in this region in thousands of breast and ovarian cancer patients and identified SNPs associated with three genes, which were analysed with functional studies.

Harnessing biomolecular systems to endow synthetic materials with life-like properties is a significant challenge. Here, the authors use the biomolecular KaiABC circadian clock proteins to control autonomous self-assembly and oscillation of colloids.

Genome-wide association analysis of an improved telomere length score, calculated from quantitative PCR and whole-genome sequencing measurements in 462,666 individuals in the UK Biobank, identifies novel genes and variants underlying this trait.

Some cancers occur in spatially constrained tissues such as the mammary gland, and how the morphological features influence the evolution of the cancer is unclear. Here, the authors use mathematical modeling to study the question of competition for space and provide inferences on the mode of evolution of cancers in such tissues.

Time-series observations from the JWST of the transiting exoplanet WASP-39b show gaseous water in the planet’s atmosphere and place an upper limit on the abundance of methane.

In this largest whole-exome sequencing study of epilepsies to date, the Epi25 Collaborative identified extremely rare variants that confer risk for diverse epilepsy subtypes, highlighting roles in synaptic transmission and neuronal excitability.

Clinical testing of BCR inhibition on DLBCL reveals determinants of response.

Influenza A viruses pose a continuing pandemic threat to humans. Le Sage, et al. describe a pandemic triage pipeline to evaluate the pandemic risk of emerging viruses and utilize it to characterize two widespread swine influenza A viruses.

1000 Genomes imputation can increase the power of genome-wide association studies to detect genetic variants associated with human traits and diseases. Here, the authors develop a method to integrate and analyse low-coverage sequence data and SNP array data, and show that it improves imputation performance.

Observations of optical flares from AT2022tsd (the ‘Tasmanian Devil’) show that they have durations on the timescale of minutes, occur over a period of months, are highly energetic, are probably nonthermal and have supernova luminosities.

Xenotransplantation in humans using pig organs could improve the transplant organ supply. Here the authors transplant pig kidneys into a brain-dead recipient and monitor the human immune cell response early after transplantation using spatial and single cell transcriptomics and show early myeloid cell infiltration.

A primordial carbon-to-oxygen ratio (C/O) greater than 0.8 in an exoplanet causes a carbide-dominated interior, as opposed to the silicate-dominated composition found on Earth; the atmospheres also can differ from those in the Solar System. The solar C/O is 0.54. This study reports an analysis of spectra from the transiting hot Jupiter WASP-12b that reveals that C/O>1 in its atmosphere, based upon the observed concentrations of the prominent molecules CO, CH₄ and H₂O.

Type 2 Long QT syndrome is a cardiac disease associated with hundreds of individual mutations within the Kv11.1 potassium channel. Here, the authors systematically investigate the trafficking defects associated with different types of Kv11.1 mutations and to what extent they can be corrected pharmacologically.

PARG catalyzes the removal of poly(ADP-ribose) (PAR) from target proteins and executes critical functions in the DNA damage response. Here the authors provide structural and biological insight with small molecule PARG inhibitors and show that PARG inhibition sensitizes cells to ionizing radiation and kills cancer cells through replication fork defects.

The Cancer Genome Atlas consortium reports on their genome-wide characterization of somatic alterations in colorectal cancer; in addition to revealing a remarkably consistent pattern of genomic alteration, with 24 genes being significantly mutated, the study identifies new targets for therapeutic intervention and suggests an important role for MYC-directed transcriptional activation and repression.

Integrating silencing RNA into the backbone of a microRNA that is highly enriched in small extracellular vesicles reduces the therapeutic dose of the silencing RNA.

Warmer spring temperatures affect the timing of stem diameter growth of temperate deciduous trees but have little effect on annual growth.

Murthy et al. demonstrate that cancer-associated fibroblast-derived acetate regulates polyamine homeostasis via an ACSS2–SP1–SAT1 axis in pancreatic cancer cells, thus enabling cell survival and tumour development under acidosis.

Common genetic variants associated with plasma lipids have been extensively studied for a better understanding of common diseases. Here, the authors use whole-genome sequencing of 16,324 individuals to analyze rare variant associations and to determine their monogenic and polygenic contribution to lipid traits.

An epidural spinal cord stimulation system regulates blood pressure in the acute and chronic phases of spinal cord injury.

Shlien and colleagues report on 300 patients from the SickKids Cancer Sequencing program and identify clinically actionable variants in 56% of the patients by profiling somatic and germline data at multiple clinical time points.

The authors present an approach to connect polymer dynamics to force response by integrating optical tweezers with differential dynamic microscopy. They measure blends of ring and linear DNA and observe a resonant response, which is suppressed by the presence of microtubules.

Bradley Bernstein, Birgit Knoechel and colleagues identify super-enhancer translocations that drive overexpression of MYB in adenoid cystic carcinoma (ACC). They find that MYB binds to the translocated enhancers and to other active enhancers that drive different regulatory programs in alternate cell lineages in ACC.

Genome-wide CRISPR screens in mouse cancer cell lines are used to identify a core, conserved set of genes and pathways that govern how cancer cells evade killing by cytotoxic T lymphocytes.

The genetic basis of primary sclerosing cholangitis has only been partially uncovered. Here, the authors perform a multitrait genome-wide association study to provide insight into the genetic etiology of primary sclerosing cholangitis risk and possible therapeutic drug targets.

The approximately 5-Gb tuatara (Sphenodon punctatus) genome assembly provides a resource for analysing amniote evolution, and highlights the imperative for meaningful cultural engagement with Indigenous communities in genome-sequencing endeavours.

Paul Brennan, Stephen Chanock and colleagues performed a genome-wide association study for renal carcinoma. They identified two genetic susceptibility loci.

Michael Talkowski and colleagues analyze balanced chromosomal abnormalities in 273 individuals by whole-genome sequencing. Their findings suggest that sequence-level resolution improves prediction of clinical outcomes for balanced rearrangements and provides insight into pathogenic mechanisms such as altered gene regulation due to changes in chromosome topology.

Targeting TBK1 is an effective strategy to overcome resistance to cancer immunotherapy.

This paper describes molecular subtypes of cervical cancers, including squamous cell carcinoma and adenocarcinoma clusters defined by HPV status and molecular features, and distinct molecular pathways that are activated in cervical carcinomas caused by different somatic alterations and HPV types.

O’Donnell and colleagues report that activation of the integrated stress response in non-small cell lung cancer cells by impairing heme production leads to enhanced PD-L1 translation in an eIF5B-dependent manner.

Radial glial progenitors (RGPs) in the developing mouse cortex generate excitatory neurons during development. This study examines the role of centriole-related protein Sas4, the mutation of which causes microcephaly in human brain, and shows that centrosome and centriole act to anchor RGPs in the ventricular zone during embryonic neurogenesis. By preventing cell death of RGPs without centrioles, the study also shows that cleavage plane orientation of cell division is not essential for radial glial progenitors' self-renewal.

An exome-wide association study of six smoking phenotypes in up to 749,459 individuals identifies associations of rare coding variants in CHRNB2 that may reduce the likelihood of smoking.

The identification of high-affinity molecular mimicry between the Epstein–Barr virus (EBV) transcription factor EBNA1 and the CNS protein GlialCAM provides a mechanistic link between multiple sclerosis and EBV.

Circulating lipoprotein(a) is an important risk factor for cardiovascular disease and shows variability between different ethnic groups. Here, Zekavat et al. perform whole-genome sequencing in individuals of European and African ancestries and find ancestry-specific genetic determinants for lipoprotein(a) levels.

We report the outcome of an international optical observation campaign of a prototype constellation satellite, AST SpaceMobile’s BlueWalker 3, which features a 64.3 m² phased-array antenna and a launch vehicle adaptor.

Diehn and colleagues report that assaying circulating DNA in patients receiving chemoradiation therapy for non-small-cell lung cancer could identify the patients most likely to benefit from consolidation immunotherapy.

Abiraterone acetate (AA) is indicated for the treatment of patients with metastatic castrate-resistant prostate cancer. Here, the authors show that, in prostate cancer patients, orally administered AA remodels the gut microbiome and promotes the enrichment of the commensal bacterium Akkermansia muciniphila at the expense of androgen-utilizing Corynebacterium species.

A mouse model of Down syndrome (DS) highlights the importance of triplication of the IFNR gene cluster for a variety of DS-associated traits. Copy number correction resulted in amelioration of multiple phenotypes associated with the condition.

In this study, the authors identify and validate a halogen-substituted isoflavanone able to inhibit prostate cancer cell motility, invasion and metastasis in vitro and in vivo. They demonstrate its ability to selectively inhibit activation of client proteins that stimulate cell motility.

As the performance of silicon-based qubits has improved, there has been increasing focus on developing designs that are compatible with industrial processes. Here, Jock et al. exploit spin-orbit coupling to demonstrate full, all-electrical control of a metal-oxide-semiconductor electron spin qubit.

City-level analysis of data from the SALURBAL project shows vast heterogeneity in life expectancy across cities within the same country, in addition to substantive differences in causes of death among nine Latin American countries, revealing modifiable factors that could be leveraged by municipal-level policies aimed toward improving health in urban environments.