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

Tan and colleagues present “cycling molecular assemblies” that borrow cellular lipidation machinery to build nanostructures inside the Golgi apparatus. These tools enable rapid organelle imaging and selective destruction of cancer cells.

Fractional Chern insulators have been observed in moiré MoTe₂ at zero magnetic field, but the expected zero longitudinal resistance has not been demonstrated. Now it is shown that improving device quality allows this effect to appear.

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.

Sexual dimorphism is common in nature. Here, the authors combine population genetics and functional experiments to show that a region containing the gene tan contributes to sex-limited colour dimorphism in Drosophila erectaand that this dimorphism has likely been adaptively maintained for millions of years.

Synapse dysfunction contributes to cognitive decline with age. Here, the authors show that aging-related changes in microglia and the extracellular matrix are associated with synapse abundance, extracellular matrix buildup, and cognitive deficits in aging mice.

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.

Global Burden of Disease estimates show that between 1990 and 2023, the prevalence and burden of drug use disorders, inclusive of amphetamine, cannabis, cocaine and opioid use, have been increasing in high-income countries, particularly in the USA.

Findings from a tectonically active mountain range show that soil production is driven by bottom-up rock weakening rather than by soil thickness, challenging long-held top-down models.

TGF-β stimulated tumor-associated neutrophils (TANs) can exert pro-tumoral functions. Here the authors show that Smad3 activation in TANs is associated with an N2-like polarization state and poor outcome in patients with non-small cell lung carcinoma and that Smad3 targeting reprograms TANs to an antitumor state suppressing tumor growth in preclinical lung cancer models.

NatD is an acetyltransferase responsible for N-α-terminal acetylation of the histone H4 and H2A and has been linked to cell growth. Here the authors show that NatD-mediated acetylation of histone H4 serine 1 competes with the phosphorylation by CK2α at the same residue thus leading to the upregulation of Slug and tumor progression.

De novo domestication was performed on the brassica Thlaspi arvense (pennycress) by identifying and stacking CRISPR-induced mutations to create a new intermediate oilseed crop that can be grown in the off-season, with seed compositions similar to canola (low erucic acid and reduced glucosinolate).

MARSIS attenuation and thermal data confirm that liquid brines are the most plausible source for the bright reflections at the base of the South Polar Layered Deposits. Such results also justify why SHARAD does not penetrate to the base of the ice.

MK-7762 is a new oxazolidinone antitubercular agent that is structurally similar to linezolid, and demonstrated in vivo efficacy, lesion penetration and limited toxicity compared to linezolid, indicating it could be used in broad tuberculosis regimens.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

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.

Khufu’s Pyramid is one of the largest archaeological monuments in the world, and still contains unexplored voids. Here, the authors use cosmic-ray muon radiography in multiple positions to precisely characterize one of these inner structures called the North Face Corridor.

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

Xenotransplantation of a genetically edited pig kidney with a thymic autograft into a brain-dead human for 61 days with immunosuppression resulted in stable kidney function without proteinuria, and xenograft rejection was treated and reversed by the end of the study.

dSHERLOCK is a nucleic acid platform for the quantification of double-stranded DNA targets using CRISPR/Cas and isothermal amplification and is applied to quantify pathogen C. auris in clinical surveillance swab samples.

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.

Here the authors show that persistent antigen stimulation drives the generation of CD8⁺ tissue-resident exhausted T cells with distinct developmental origins, function and therapeutic responsiveness when compared to CD8⁺ tissue-resident memory T cells.

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.

The Schrödinger impact event carved two canyons on the moon comparable in size to the Grand Canyon of North America. The directions of those canyons imply little debris covers the > 4-billion-year-old units that will be explored by Artemis astronauts.

The authors create a distributed sensor array that achieves optical super-resolution without lenses, using computational synchronization to combine multiple sensors and expand imaging areas 16-fold beyond physical sensor dimensions.

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.

The author demonstrates that laser-driven ultracold Fermi gases can exhibit color-orbit-like coupling with SU(3) symmetry. This leads to color-like oscillations and other quantum-chromodyamics-like phenomena in an atomic physics laboratory.

Transition metal nitride coatings exhibit high hardness, but typically lack ductility and are therefore prone to failure. Here, the effect of bilayer thickness on the mechanical properties of MoN-TaN superlattices is investigated, leading to coatings with high fracture toughness.

Rider, Grantham, Smith, Watson et al. integrate multiomic data from patients with psoriasis using dimensionality reduction and machine learning techniques. This approach identifies biological relationships between genetic background, clinical features and disease severity, providing insight into disease variability across individuals.

In this work, the authors show that the essential Mycoplasma pneumoniae protein P116 enables cholesterol acquisition from lipoproteins and various cell types. An antibody against its C-terminal domain inhibits lipid acquisition, growth, and plaque binding, linking M. pneumoniae to atherosclerotic lipid-rich tissue.

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.

Recent MPXV outbreaks underscore the need for better vaccines and treatments. Here, the authors isolate and structurally characterize potent antibodies interacting with A28 that they identify as a key viral surface protein essential for viral entry and that induces strong, protective antibody response in mice.

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.

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.

There are limited in vitro and in vivo models to study human fetal exposure to environmental noise. Here, the authors develop a computational model to quantify fetal exposure to acoustic fields, obtaining acoustic transfer characteristics across the human audio range.

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.

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.

Drosophila Microproteins Simba1/2 act in neural stem cells and blood-brain-barrier glia to promote reactivation of neural stem cells via activating WNT/Wingless signaling, while human ortholog ZNF706 is found to have a conserved role in activating WNT pathway.

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

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.

Results from the phase ELAD 2 trial reveal that liraglutide is safe and well tolerated in people with mild to moderate Alzheimer’s disease but does not significantly slow brain metabolism decline.

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.

Nematicity, the spontaneous breaking of lattice rotational symmetry, plays an important role in kagome metals. Here, the authors report on a nematic phase within seven Kelvin below the charge density wave transition in the bilayer kagome metal ScV₆Sn₆.

T-cell acute lymphoblastic leukemia is a highly aggressive disease with varying recurrence rates. Here, the authors build a single cell transcriptomic atlas of childhood T-cell acute lymphoblastic leukaemia (T-ALL). They identified a distinctive cancer cell state that correlates with high risk, treatment refractory T-ALL.

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.

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.

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

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.

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.