Search

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

Zhou, Ho and colleagues show that, in mice, a schizophrenia-associated mutation impairs belief updating by weakening mediodorsal (MD) thalamus activity. Boosting this activity restored flexible decision-making, suggesting MD thalamus as a potential therapeutic target.

Most advanced triple-negative breast cancers remain resistant to immunotherapy. Here, the authors discover that RIPK1-driven necroptosis in both tumor and stromal compartments is essential for effective immunogenic cell death-based therapy and immune checkpoint blockade.

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.

We present a sustainably sourced adhesive system, with performance comparable to that of current industrial products, made from epoxidized soy oil, malic acid and tannic acid, all biomass derived, low cost and readily available.

Introduction of structured neutron waves carrying orbital angular momentum (OAM) in small-angle neutron scattering experiments provides novel approaches to the characterisation of material properties. Here the authors demonstrate the retrieval of phase information in far-field intensity profiles by means of an interferometric technique using helical neutron waves.

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.

Disentangling intertwined orders in quantum materials is challenging. Now, photoemission spectroscopy experiments show that magnetic fields can be used to disentangle such orders in a kagome superconductor.

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.

Climate change threatens the future of the Antarctic Ice Sheet. Here the authors show that individual drainage basins have different thresholds and loss patterns, suggesting the need to consider the dynamical interactive nature of the basins and their individual tipping points.

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.

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.

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.

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.

This work highlights how changes to beaches are related to sand movement and human impacts to the coast and illuminates opportunities for sand management to resolve shoreline erosion and enhance beach sustainability.

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.

STAARpipeline is a comprehensive framework for flexible and scalable rare-variant association analysis using whole-genome sequencing data and annotation information.

Electrically conductive hydrogels based on conducting polymers often rely on covalent and therefore irreversible crosslinking mechanisms. Here, the authors report a thermo-responsive conducting polymer that undergoes a fully reversible non-covalent crosslinking at 35 °C within less than a minute to form conductive hydrogels.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

Multiomic single-cell analyses of 15 Down syndrome fetal cortical samples identify widespread disruption of neurodevelopmental transcriptional programs, driven by three dosage-sensitive chromosome 21 transcription factors.

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.

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.

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

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.

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.

Fast panoramic rotational ultrasound tomography and photoacoustic tomography are integrated for hybrid rotational ultrasound and photoacoustic tomography, for three-dimensional dual-contrast imaging of soft tissue and vasculature across the human body.

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.

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.

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.

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.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole 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.

 A bifunctional iminophosphorane-catalysed, stereo-controlled deconjugation for the synthesis of highly enantioenriched alkylidenecyclopropanes is described, alongside computational studies elucidating the mechanistic pathway and origins of diastereoselectivity and enantioselectivity.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

In an integrated analysis of transcriptomic data from the SUBSPACE consortium and public datasets of patients with sepsis, acute respiratory distress syndrome, trauma and burns, dysregulation within four consensus molecular clusters related to myeloid and lymphoid cells is associated with mortality and illness severity.

Mapping of the neutrophil compartment using single-cell transcriptional data from multiple physiological and patological states reveals its organizational architecture and how cell state dynamics and trajectories vary during health, inflammation and cancer.

This protocol uses Reprogrammable Adenosine Deaminase Acting on RNA (ADAR) Sensors (RADARS) to robustly sense RNA transcripts inside eukaryotic cells, enabling detection of changes in gene expression or targeting and perturbation of specific mammalian cell types and states.

Laser-induced tuning of pairs of lifetime-limited organic emitters allows the controlled creation of superradiant and subradiant entangled states.

Small lightning flashes detected on Jupiter by Juno have shallow origins above the 2-bar level of Jupiter’s atmosphere where temperatures are too low for liquid water to exist.

Light represses biofilm formation and production of virulence factors in the pathogenic bacterium Pseudomonas aeruginosa. Here, Manias et al. identify a periplasmic microprotein that regulates this process by activating the degradation of a component of the light-sensing pathway.

The authors demonstrate that stable partial polarization control achieves more than 10¹⁰ write cycles in ferroelectric AlScN. Further, reducing capacitor diameter increases breakdown voltage, boosting endurance.

STAAR is a powerful rare variant association test that incorporates variant functional categories and complementary functional annotations using a dynamic weighting scheme based on annotation principal components. STAAR accounts for population structure and relatedness and is scalable for analyzing large whole-genome sequencing studies.

REMETA is a method for meta-analyzing gene-based associations using summary statistics, integrating with REGENIE and improving computational efficiency for large studies with many phenotypes.

MetaSTAAR enables functionally informed rare variant association analysis in biobank-scale cohorts using an efficient, sparse matrix approach for summary statistic storage.

Masers are promising for applications that use microwave radiation. Here, the authors present a compact room-temperature maser design using a high permittivity dielectric material for the resonator to achieve low optical pumping powers. This design pushes masers closer towards their promised applications.

SpaceX’s Inspiration4 mission sent an all-civilian crew into orbit to study physiological, neurovestibular and neurocognitive changes in the astronauts and found that short-duration civilian space missions do not pose a major health risk.