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Modeling of per-cell perturbation states in single-cell RNA sequencing datasets enhances detection of response expression quantitative trait loci and helps prioritize genetic regulatory effects in disease-relevant contexts.

The dysregulation of the m⁶A epitranscriptomic networks have been reported to contribute to the development of gliomas. Here, the authors utilize induced pluripotent stem cell-derived astrocytes with a p53 mutation and demonstrate that mutant p53 upregulates the m⁶A reader YTHDF2, resulting in the initiation of gliomas.

Nathan Pankratz, Santhi Ganesh and colleagues use exome chip data to identify rare and common variants influencing blood cell traits. They report associations at several loci, including a rare missense variant in S1PR4 associated with circulating neutrophil counts, and present functional studies supporting a role for S1PR4 in neutrophil recruitment and resolution in response to tissue injury.

Building atomistic models with molecules of varying size and density requires significant time and expertize. Here, authors describe CHARMM-GUI Multicomponent Assembler that guides complex molecular assembly and simulation input preparation under periodic boundary conditions.

Variant-to-gene-to-program is a new approach to building maps of genome function to link risk variants to disease genes and to convergent signalling pathways in an unbiased manner; its strength is demonstrated in coronary artery disease.

A comprehensive single-cell RNA sequencing study delineates cell-type-specific transcriptomic changes in the brain associated with normal ageing that will inform the investigation into functional changes and the interaction of ageing and disease.

A microfluidics- and electron-microscopy-based method enables the characterization of polyclonal antibody responses to infection and vaccination.

SnapATAC2 uses a matrix-free spectral embedding algorithm for nonlinear dimension reduction of single-cell omics data, which shows an improved performance in capturing cellular heterogeneity and scalability for large datasets.

A multi-ancestry meta-regression study analyses diverse genome-wide association studies and genome loci associated with tobacco and alcohol use.

Ataxia telangiectasia is a genetic disease that results in various pathological disorders. In this study, the authors develop an in vitromodel of Ataxia telangiectasia using human induced pluripotent stem cells, and find that physiological defects can be alleviated by small molecule read-through compounds.

Interrogation of neuronal autophagy in vivo in Alzheimerʼs disease mouse models identified deficient autolysosome acidification as the basis for extreme autophagic stress, yielding β-amyloid accumulation within intact neurons, which are the main source of senile plaques.

Analysing camera-trap data of 163 mammal species before and after the onset of COVID-19 lockdowns, the authors show that responses to human activity are dependent on the degree to which the landscape is modified by humans, with carnivores being especially sensitive.

A multi-ancestry genome-wide association meta-analysis of kidney cancer identifies 63 regions associated with disease susceptibility including one locus that was associated with increased risk in individuals with African ancestry.

By comparing neural responses to diverse visual stimuli measured with a standardized two-photon imaging pipeline, the authors reveal response specializations within the mouse visual cortex.

Phase-resolved mid-infrared observations from JWST of the hot gas giant WASP-43b detect a day–night difference of 659 ± 19 K. Comparison with climate models shows that the observations are compatible with cloudy skies, at least on the nightside, and the lack of methane detection suggests the presence of disequilibrium chemistry.

A meta-prediction framework integrating polygenic risk scores spanning multiple conditions and nongenetic factors, such as laboratory tests and baseline diagnoses, had superior performance in predicting the 10-year risk of coronary artery disease compared with standard clinical scores and previously developed polygenic risk scores.

One hundred and ten Zika virus genomes from ten countries and territories involved in the Zika virus epidemic reveal rapid expansion of the epidemic within Brazil and multiple introductions to other regions.

Using a CRISPR interference genetic approach, Bullen, Johnson, and colleagues discover a type IV restriction (TIV-RE) enzyme encoded on a mobilizable plasmid of multidrug resistant Enterococcus faecalis. This TIV-RE is a potent inhibitor of bacteriophage infection.

Efficient, large-scale genomic analysis is facilitated on the cloud by a computational tool with error-diagnosing and self-healing capabilities.

Post-traumatic stress disorder (PTSD) is a common mental health problem. Here, the authors report a GWAS from the Psychiatric Genomics Consortium in which they identify two risk loci in European ancestry and one locus in African ancestry individuals and find that PTSD is genetically correlated with several other psychiatric traits.

Bosonic qubits can be engineered to feature intrinsic protection against certain kinds of errors, which makes quantum error correction across many bosonic qubits possible with less overhead.

The authors employ a polygon-based ultrafast delay scanner and a deep learning framework for acquiring stimulated Raman scattering spectrum with high spectral and temporal resolution. They demonstrate high-speed imaging and tracking of multiple biomolecules in the fingerprint region.

Hefzi et al. engineer cells to nearly eliminate lactate production and increase mitochondrial use of pyruvate by deleting both lactate dehydrogenases and pyruvate dehydrogenase kinases with the goal of circumventing pH and osmolarity issues that arise in bioreactor-based production of biopharmaceuticals.

This study reports that nuclear speckle constituents have two expression states in cancer correlating with patient survival and HIF-2α functional programs. HIF-2α mediates nuclear speckle association of key genes activated in renal cancer.

Understanding how copper nanoparticles evolve under electrochemical conditions is crucial for the development of selective CO₂ reduction electrocatalysts. Here the authors prepare well-defined nanocrystals and use advanced operando imaging and spectroscopic techniques to reveal the Cu–CO species-driven dynamic evolution of Cu electrodes.

Analysis of whole-genome sequencing data across 2,658 tumors spanning 38 cancer types shows that chromothripsis is pervasive, with a frequency of more than 50% in several cancer types, contributing to oncogene amplification, gene inactivation and cancer genome evolution.

A single-cell multiomics analysis of over 200,000 cells of the primary motor cortex of human, macaque, marmoset and mouse shows that divergence of transcription factor expression corresponds to species-specific epigenome landscapes, and conserved and divergent gene regulatory features are reflected in the evolution of the three-dimensional genome.

Emerging SARS-CoV-2 variants of concern were detected early and multiple cases of virus spread not captured by clinical genomic surveillance were identified using high-resolution wastewater and clinical sequencing.

van der Waals magnets can be arranged into twisted heterostructures, with the twisting leading to the formation of new magnetic phases. Here, Li, Sun, and coauthors show via NVcentre based magnetometry small angle twisted double trilayer CrI₃ exhibits a co-existing, hybrid magnetic phase with distinct phase transition temperatures.

Cognitive function is associated with health and important life outcomes. Here, the authors perform a genome-wide association study for general cognitive function in 300,486 individuals and identify genetic loci that implicate neural and cell developmental pathways in this trait.

An extensive map of human DNase I hypersensitive sites, markers of regulatory DNA, in 125 diverse cell and tissue types is described; integration of this information with other ENCODE-generated data sets identifies new relationships between chromatin accessibility, transcription, DNA methylation and regulatory factor occupancy patterns.

Data collected from more than 2,000 taxa provide an unparalleled opportunity to quantify how extreme wildfires affect biodiversity, revealing that the largest effects on plants and animals were in areas with frequent or recent past fires and within extensively burnt areas.

Single-cell genomics has expanded to measure diverse molecular modalities within the same cell. Here the authors provide a computational framework called scTriangulate to integrate cluster annotations from diverse independent sources, algorithms, and modalities to define statistically stable populations.

An initial draft of the human pangenome is presented and made publicly available by the Human Pangenome Reference Consortium; the draft contains 94 de novo haplotype assemblies from 47 ancestrally diverse individuals.

Why joints are highly responsive to systemic inflammation is unknown. Hasegawa et al. sought to address this question, developing a whole-mount imaging system of the entire synovium to profile the vascular, neuronal and immune components.

Concentrated water infiltration was detected in 46% of Australian groundwater bores across arid and wet climates, suggesting that conventional diffuse-only recharge estimates may significantly underestimate total recharge, according to Tritium data from more than 1,700 samples.

Genetic and functional studies implicate allele-specific regulation of OAS1 splicing and nonsense-mediated decay in COVID-19 severity. The OAS1 risk haplotype is also associated with reduced SARS-CoV-2 clearance in a clinical trial with pegIFN-λ1.

Loss of tumor suppressor function is one of the major causes of uncontrolled growth of cancer cells. Here authors show that inactivation of the tumor suppressors NF1, TSC1, and TGF-β RII also promotes a non-cell autonomous change in the tumor microenvironment, characterized by inflammatory features and LAG3+ T cell-mediated immune suppression, which are therapeutically targetable.

A fibroblast lineage marked by FAP gives rise to POSTN-expressing fibroblasts resembling matrifibrocytes and IL-1β regulates FAP/POSTN fibroblast specification by directly signalling to cardiac fibroblasts, highlighting a role for immunomodulators in targeting cardiac fibrosis.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

We present the complete 62,460,029-base-pair sequence of a human Y chromosome from the HG002 genome (T2T-Y) that corrects multiple errors in GRCh38-Y and adds over 30 million base pairs of sequence to the reference.

A multi-ancestry genome-wide association study of problematic alcohol use in one million individuals identified 110 risk variants and shows that multi-ancestry polygenic scores improve risk prediction compared with single-ancestry scores

The integrator complex is required for the synthesis of protein coding and non-coding RNA and contains the protein INTS13. Here, the authors find germline mutations in INTS13 in two families with oral facial digital syndrome and show that the mutation affects the c-terminal domain of the protein and disrupts cilliogenesis.

The severity of ulcerative colitis, and response to treatment, is highly variable. Here, the authors examine rectal gene expression signatures and faecal microbiomes of children and adults with the disease and provide new insights in to pathogenesis.

Budding processes on cell membranes involve distortions of surface geometry, driven by the sorting of membrane components. Here, the authors model a budding process and observe spontaneous reordering of materials in the areas of high curvature, especially around bud-necks, producing ring-raft type structures.

Cortex morphology varies with age, cognitive function, and in neurological and psychiatric diseases. Here the authors report 160 genome-wide significant associations with thickness, surface area and volume of the total cortex and 34 cortical regions from a GWAS meta-analysis in 22,824 adults.