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Estimates from the Global Burden of Disease study reveal declines in chronic respiratory disease mortality between 1990 and 2023—especially during the COVID-19 pandemic—but the burdens on people affected remain substantial.

MedHELM, an extensible evaluation framework including a new taxonomy for classifying medical tasks and a benchmark of many datasets across these categories, enables the evaluation of large language models on real-world clinical tasks.

Ion diffusion region is an indicator of active magnetic reconnection, but it had not been detected in Jupiter’s magnetosphere previously. Here, the authors show a magnetic reconnection event in Jupiter’s inner magnetosphere that presents the detection of an ion diffusion region.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

The combination of computational design, laboratory-based screening and biophysical validation enables the de novo generation of variable heavy-chain antibody fragments and antibodies that precisely target chosen disease-related molecules.

Therapeutic options for patients with renal medullary carcinoma (RMC) are limited. Here the authors report the results of a phase II clinical trial of anti-PD1 nivolumab plus anti-CTLA4 ipilimumab in RMC, associating the activation of a myeloid mimicry program in tumor cells to the rapid disease progression and hyper-progression observed in treated patients.

Multiplexed editing in primary human T cells generates enhanced immune cell therapies.

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.

Genome editing tools can precisely introduce a specified lesion into the DNA, but ultimately rely on the cell’s DNA repair machinery to determine the editing outcome. Here, authors demonstrate how neurons’ unique DNA repair pathways impact the safety, efficiency, and precision of CRISPR edits.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

Neoadjuvant immunochemotherapy against NSCLC has been tested in clinical trials. Here, the authors follow up longer-term survival and measure immune cell phenotype changes in a single-arm phase II clinical trial of neoadjuvant immunochemotherapy, indicating association of intratumoural TCR diversity and CD8 T cell positioning.

Microflora Danica—an atlas of Danish environmental microbiomes—reveals that although human-disturbed habitats have high alpha diversity, species reoccur, revealing hidden homogeneity.

Meta-analyses in up to 1.3 million individuals identify 87 rare-variant associations with blood pressure traits. On average, rare variants exhibit effects ~8 times larger than the mean effects of common variants and implicate candidate causal genes at associated regions.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

Genome-wide association studies (GWAS) have improved our understanding of the genetic basis of lung adenocarcinoma but known susceptibility variants explain only a small fraction of the familial risk. Here, the authors perform a two-stage GWAS and report 12 novel genetic loci associated with lung adenocarcinoma in East Asians.

In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

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.

Here the authors perform a trans expression quantitative trait locus meta-analysis study of over 3,700 people and link a USP18 variant to expression of 50 inflammation genes and lupus risk, highlighting how genetic regulation of immune responses drives autoimmune disease and informs new therapies.

Confinement effects enable the design of intersubband polaritons (ISPs) in semiconductor quantum wells (QWs), but this type of light-matter excitations has been rarely explored in van der Waals materials. Here, the authors report the observation of hyperbolic ISPs in WO_x/WSe₂ QW heterostructures with electrically tunable dispersions.

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.

A high-bandwidth neuromotor interface offers performant out-of-the-box generalization across people.

Condensates of excitons have been observed in the quantum Hall regime, but evidence for their existence at low magnetic fields remains controversial. Now evidence of coherence between optically pumped interlayer excitons in MoS₂ marks a step towards confirming exciton condensation at low magnetic fields.

T cell responses can be generated to either pathogen infection or from priming with a vaccine. Here the authors compare T cell generation, phenotype and single cell transcriptome of participants vaccinated with a mpox vaccine or infected with the virus showing that the virus induced T cells showed more effective function and phenotype.

Dextran sulfate sodium is a colitis inducer that stimulates a ROS–Src–IP6K2 signaling axis to generate 5-IP₇, which sterically inhibits PI(4,5)P₂ phosphatases to promote PI(4,5)P₂-mediated E-cadherin endocytosis and epithelial junction breakdown.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

Samples of serum from individuals immunized with the BNT162b2 vaccine show neutralization activity against engineered SARS-CoV-2s bearing the spike mutations from B.1.617 and other variants.

Polygenic risk scores can help identify individuals at higher risk of type 2 diabetes. Here, the authors characterise a multi-ancestry score across nearly 900,000 people, showing that its predictive value depends on demographic and clinical context and extends to related traits and complications.

Over the last 15 years, the content of Nature Physics has covered an enormous breadth of subjects at the forefront of physics. The journal’s past and present editors recount their favourite papers and what made chaperoning them to publication special.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

The characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet-base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.

Multiancestry fine-mapping of brain protein quantitative trait loci coupled with Mendelian randomization analyses identifies protein–trait pairs consistent with causal effects across neurological and psychiatric conditions.

Subduction-driven warming and uplift are linked to the Cambrian Explosion, and Li-Os-Sr isotopes trace enhanced erosion of phosphorus-rich juvenile rocks that boosted productivity and oxygen levels to fuel animal diversification.

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.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

Interactions between Semaphorin-3A (SEMA3A) and Neuropilin-1 (NRP1) and Plexin-A1 and Plexin-A4 have been shown to affect T cell development. Here the authors investigate how these interactions affect CD8⁺ T cells in tumour immunity, showing that NRP-1, Plexin-A1 and Plexin-A4 are upregulated on T cells allowing tumour derived SEMA3A to inhibit CD8⁺ T cell migration and function.

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

Antibody–bottlebrush conjugates expand the options for drug cargos compared to antibody–drug conjugates.

Cooperative paramagnetism refers to a strongly correlated state without long range magnetic order that occurs in frustrated magnetic systems between the Neel temperature and Curie-Weiss temperature. Here, using resonant elastic magnetic and inelastic x-ray scattering, Terilli et al find a spectrally sharp gapped magnetic excitations that persists above the Neel temperature in Y₂Ir₂O₇, implying a cooperative paramagnetic phase.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

A quantum kernel estimation by which feature data points are evaluated through the unitary evolution of two-boson Fock states is experimentally demonstrated on a photonic integrated processor. This model provides enhanced accuracy with respect to commonly used classical methods for several classification tasks.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.