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Restricting or permitting H3K27me3 spreading concentrates or dilutes canonical PRC1 (cPRC1), respectively, which affects three-dimensional chromatin interactions. Disruption of cPRC1 compromises repression of Polycomb target genes and induces differentiation and tumor regression in H3K27M-mutant glioma.

Here the authors report real-world evidence through a retrospective analysis of a multinational cohort of 1.8 M older adults showing that GLP1RAs and SGLT2 inhibitors carry lower risk for hyperkalemia than sulfonylureas. However, SGLT2 inhibitors increased risk of ketoacidosis. Findings support safety-conscious prescribing for older adults, who are often underrepresented in clinical trials.

When 100 social and behavioural science claims were examined, 34% of reanalyses closely matched the original results, with 74% reaching the same conclusion, revealing limited robustness of single-path analyses and the need to address analytical uncertainty.

Drivers of spatial differences in leaf phenology are not as widely studied as temporal differences. Here the authors show that the spatial variation of leaf unfolding in 8 deciduous tree species in Europe can be explained by local adaptation to long-term mean climate conditions.

Robustness checks and reproduction of analyses with existing and updated data based on 110 articles in economics and political science journals with data and code-sharing requirements found high levels of robustness and reproducibility and determined that robustness was not dependent on author characteristics or data availability.

The Human Development Multiomic Atlas catalogues single-cell accessibility and gene expression data from human fetal cells across 12 organs, enabling the inference of syntactic rules for motifs that govern cell-type-specific transcription factor binding and chromatin accessibility during human development.

Pathologic transformation in Kras^G12D-mutant alveolar type II cells initiates a tumour-permissive niche by orchestrating epithelial, stromal and immune reprogramming through amphiregulin–EGFR signalling, creating a self-sustaining circuit critical for lung tumour initiation and progression.

Rapid urbanization affects both local food and ecological systems in Africa. This study integrates the effects of land-use displacement and dietary shifts associated with urbanization in scenarios of future food demand to understand the impact of future urbanization on the African environment.

u-Segment3D is a universal framework that translates and enhances 2D instance segmentations to a 3D consensus instance segmentation without training data. It performs well across diverse datasets, including cells with complex morphologies.

This multi-cohort study reports genetic variants in myostatin associated with increased muscle mass, strength, and reduced adiposity. These findings support long-term myostatin blockade for muscle preservation in the context of weight loss.

DNA-sequencing data from primary tumours and paired metastases from participants in the TRACERx lung study and PEACE autopsy programme are used to analyse the metastatic diversity of advanced non-small cell lung cancer and the seeding patterns that underpin it.

Reducing China’s CO₂ emissions is crucial to achieving global carbon neutrality. This Perspective synthesizes bottom-up and top-down estimates to develop a regional CO₂ budget for China and evaluate pathways and uncertainties towards net zero.

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.

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.

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.

The SARS-CoV-2 Nucleocapsid (N) protein serves multiple roles in the viral lifecycle. Phosphorylation toggles N between these roles by altering N’s conformation, its material properties when phase separated with RNA, and its membrane interactions.

The authors have applied an eight-tissue rat multi-omic dataset to analyze the gene regulatory landscape of endurance exercise training, identifying tissue-specific regulatory patterns involved in muscle function, metabolism and immune response.

This study explores the magnitude, spatiotemporal variation and drivers of nitrous oxide emissions from Chinese livestock production over the past four decades. Scenario analysis is used to estimate emissions mitigation potential of different measures, their associated marginal abatement costs and the social benefits.

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.

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.

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

Molecular glue degraders have consistently been discovered retrospectively, despite their increasing importance. Herein, a high-throughput approach is described that modifies existing ligands into molecular glue degraders.

The CT-RATE dataset pairs 3D chest computed tomography volumes with radiology reports to train a foundation model for medical imaging.

Here the authors provide an explanation for 95% of examined predicted loss of function variants found in disease-associated haploinsufficient genes in the Genome Aggregation Database (gnomAD), underscoring the power of the presented analysis to minimize false assignments of disease risk.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

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.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

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.

EGFR inhibitors are standard of care in patients with EGFR-mutant non-small cell lung cancer (NSCLC) but resistance often develops. Here the authors report that the evolution of EGFR inhibitor resistance in EGFR-mutant NSCLC results in a sensitivity to the compound, MCB-613, and investigate the underlying mechanism of action.

KRAS mutations are keenly associated with pancreatic ductal adenocarcinoma and represent a potential therapeutic target. Here the authors present the findings from a phase I clinical trial testing pooled KRAS mutant peptides in combination with immune checkpoint blockade in patients with resected pancreatic ductal adenocarcinoma.

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.

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

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.

Existing datasets of nitrogen (N) balance in agriculture are often discrepant. Comparing 13 of them regarding five metrics (fertilizer application, manure application, biological N fixation, atmospheric deposition, and N harvested as crop products) over 1961–2015 reveals why. Recommendations for improving N quantification and an N budget benchmark dataset are also proposed.

Verification of reported fossil fuel emissions is critical for tracking the progress of the Paris Agreement. Here, a simple model suggests the stability of the sensitivity of net carbon exchange to climate and carbon dioxide forcing and validates reported global emissions with improved accuracy.

Biased noise qubits, which can selectively suppress certain types of noise, are advantageous for quantum error correction of bosonic codes. Here the authors make an important step in this direction by demonstrating quantum control of a harmonic oscillator with a biased noise qubit.

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.

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.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

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.

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

Topological effects known from condensed matter physics have recently also been explored in photonic systems. Here, the authors directly observe topological surface-state arcs in momentum space by near-field scanning the surface of a chiral hyperbolic metamaterial.