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cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

The medium-resolution transmission spectrum of the exoplanet WASP-39b, described using observations from the Near Infrared Spectrograph G395H grating aboard JWST, shows significant absorption from CO₂ and H₂O and detection of SO₂.

Optical clock networks have many applications from precision time keeping, sensing to fundamental physics. Here the authors demonstrate robust and free-space femtosecond time synchronization of optical clocks via a moving quadcopter.

The authors present DIGIT, a Bayesian imaging method that maps quantum emitters to lattice sites, achieving 0.178 Å precision and a new exponential scaling law, enabling massively parallel, sub-ångström localization in quantum and biological systems.

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).

High-depth sequencing of non-cancerous tissue from patients with metastatic cancer reveals single-base mutational signatures of alcohol, smoking and cancer treatments, and reveals how exogenous factors, including cancer therapies, affect somatic cell evolution.

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.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Zhang et al. identify and characterize supermeres as extracellular nanoparticles that exhibit unique biological and functional properties with potential prognostic and therapeutic value across distinct diseases.

A conserved feature of metazoan meiosis is that it occurs in a syncytium. Here, the authors show that intercellular bridges that connect germ cells in a syncytium are critical for ensuring proper meiotic progression and fertility in male mice.

Two ‘outrigger’ telescopes were added to CHIME, leading to the localization at detection of FRB 20210603A. The burst originated from deep within the star-forming disk of its host galaxy.

A study reports a quantum gravity gradient sensor with a design that eliminates the need for long measurement times, and demonstrates the detection of an underground tunnel in an urban environment.

In lung adenocarcinoma, antibodies against endogenous retroviruses promote anti-tumour activity, and expression of endogenous retroviruses can predict outcomes of immunotherapy.

Allelic variants for the HIV-1 co-receptors chemokine receptor 5 (CCR5) and CCR2, as well as the ligand for the co-receptor CXCR4, stromal-derived factor (SDF-1), have been associated with a delay in disease progression. We began this study to test whether polymorphisms in the CCRS regulatory regions influence the course of HIV-1 disease, as well as to examine the role of the previously identified allelic variants in 1,090 HIV-1 infected individuals. Here we describe the evolutionary relationships between the phenotypically important CCRS alleles, define precisely the CCR5 regulatory sequences that are linked to the CCR5-Δ32 and CCR2-64I polymorphisms, and identify genotypes associated with altered rates of HIV-1 disease progression. The disease-retarding effects of the CCR2-64I allele were found in African Americans but not in Caucasians, and the SDF1-3′A/3′A genotype was associated with an accelerated progression to death. In contrast, the CCR5-Δ32 allele and a CCR5 promoter mutation with which it is tightly linked were associated with limited disease-retarding effects. Collectively, these findings draw attention to a complex array of genetic determinants in the HIV-host interplay.

Integrated multi-omic analyses using samples from the TRACERx study highlight cross-talk between DNA hypermethylation and genomic lesions in non-small cell lung cancer.

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.

Large genome-wide meta-analysis of clinically diagnosed late-onset Alzheimer’s disease (LOAD) from 94,437 individuals identifies new LOAD risk loci and implicates Aβ formation, tau protein binding, immune response and lipid metabolism.

Computational and machine-learning approaches that integrate genomic and transcriptomic variation from paired primary and metastatic non-small cell lung cancer samples from the TRACERx cohort reveal the role of transcriptional events in tumour evolution.

Swanton and colleagues present a clonal expression signature, ORACLE, which, in combination with clinicopathological and molecular risk factors, can predict survival of patients with lung adenocarcinoma, and they prospectively validate its prognostic value.

Combination of epidemiology, preclinical models and ultradeep DNA profiling of clinical cohorts unpicks the inflammatory mechanism by which air pollution promotes lung cancer

A longitudinal evolutionary analysis of 126 lung cancer patients with metastatic disease reveals the timing of metastatic divergence, modes of dissemination and the genomic events subject to selection during the metastatic transition.

African ancestry is a known risk factor for prostate cancer development, but the genetic determinants of this are incompletely understood. Here, the authors identify 172 potentially pathogenic variants which are enriched in an African population.

Analyses of the TRACERx study unveil the relationship between tissue morphology, the underlying evolutionary genomic landscape, and clinical and anatomical relapse risk of lung adenocarcinomas.

Using multi-ancestry genome-wide association study and fine-mapping, 298 loci and 36 credible genes are identified in the aetiology of bipolar disorder.

Electron-electron interactions in many-body systems may manifest themselves through the fractional quantum Hall effect. Here, the authors perform transport measurements in bilayer graphene, and observe particle-hole symmetric fractional quantum Hall states in theN=2 Landau level.

Major histocompatibility complex (MHC) loss of heterozygosity, allele-specific mutation and measurement of expression and repression (MHC Hammer) detects disruption to human leukocyte antigens due to mutations, loss of heterogeneity, altered gene expression or alternative splicing. Applied to lung and breast cancer datasets, the tool shows that these aberrations are common across cancer and can have clinical implications.

Observations from the JWST MIRI/LRS show the detection of SO₂ spectral features in the 5–12-μm transmission spectrum of the hot, Saturn-mass exoplanet WASP-39b, suggesting that photochemistry is a key process in high-temperature exoplanet atmospheres.

A meta-analysis of genome-wide association studies of type 2 diabetes (T2D) identifies more than 600 T2D-associated loci; integrating physiological trait and single-cell chromatin accessibility data at these loci sheds light on heterogeneity within the T2D phenotype.

Results of the TRACERx study shed new light into the association between body composition and body weight with survival in individuals with non-small cell lung cancer, and delineate potential biological processes and mediators contributing to the development of cancer-associated cachexia.

The International Strawberry Sequencing Consortium reports the draft genome of the woodland strawberry (Fragaria vesca). The genome of this diploid species should serve as a reference genome for the Fragaria genus, as the cultivated strawberry (Fragaria × ananassa) is an octoploid where F. vesca is predicted to be a subgenome donor.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

Measurements of subclonal expansion of ctDNA in the plasma before surgery may enable the prediction of future metastatic subclones, offering the possibility for early intervention in patients with non-small-cell lung cancer.

Analyses of multiregional tumour samples from 421 patients with non-small cell lung cancer prospectively enrolled to the TRACERx study reveal determinants of tumour evolution and relationships between intratumour heterogeneity and clinical outcome.

Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.

A cyclic octapeptide labelled with a near-infrared dye and that binds, with high affinity at high levels of calcium, to phosphorylated protein Annexin A2 in a range of solid tumours, serves as a tumour-selective imaging probe.

Wu et al. utilize multiparametric analysis of early-stage human NSCLC to characterize a population of Vδ1 T cells displaying a resident memory and effector memory phenotype, which were associated with ongoing remission.

A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.

Patient-derived xenografts are important tools for cancer drug development. Here, the authors develop models from 22 non-small cell lung cancer patients. They show genomic differences between models created from different spatial regions of tumours and a bottleneck on model establishment.

Mixed responses to targeted therapy within a patient are a clinical challenge. Here the authors show that TP53 loss-of-function cooperates with whole genome doubling which increases chromosomal instability. This leads to greater cellular diversity and multiple routes of resistance, which in turn promotes mixed responses to treatment.

Oncogene cooperation enhances PD-L1 translation to promote immune evasion and metastasis in a novel model of liver cancer.

Genome-wide association analyses of 41,917 bipolar disorder cases and 371,549 controls of European ancestry provide new insights into the etiology of this disorder and identify novel therapeutic leads and potential opportunities for drug repurposing.

Mutations in LSM11 and RNU7-1, which encode components of the replication-dependent histone pre-mRNA–processing complex, cause an autoinflammatory syndrome due to enhanced interferon signaling mediated by the cGAS–STING pathway, showing an essential role for nuclear histones in suppressing the immunogenicity of self-DNA.

The age-related decline in the regenerative capacity of muscle can be reversed in mice by exposure to young circulation. Elabd et al.identify the hormone, oxytocin, as a potential mediator of this effect, showing that its plasma levels decline with age and that administration of oxytocin to aged mice improves muscle regeneration.

A survey of T cell repertoire evolution in the tumors, healthy tissue and blood of patients with early-stage untreated lung cancer offers an opportunity to monitor and identify neoantigen-specific T cells for personalized immunotherapy.

The expression of each of the roughly 22,000 genes of the mouse genome has been mapped, at cellular resolution, across all major structures of the mouse brain, revealing that 80% of all genes appear to be expressed in the brain.