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Authors used targeted long-read sequencing to facilitate the discovery of rare and novel HBV RNAs in the infected liver. They identified differential promoter activity with potential implications for drug resistance and cancer.

Massively parallel reporter assay in primary human CD4⁺ T cells and bulk and single-cell CRISPR-interference screens identify candidate causal variants linked to autoimmune disease risk that modulate T cell gene expression and proliferation.

Closely related species often have different sex-chromosome systems, but it is not known whether sex-chromosome turnover contributes to the evolution of reproductive isolation between species. Here, a neo-sex chromosome is identified in only one member of a sympatric species pair of stickleback fish in Japan. The newly evolved sex chromosome is found to contain genes that contribute to speciation, suggesting that sex-chromosome turnover might have a greater role in speciation than was previously appreciated.

Premier vows to improve energy efficiency and curb pollution and carbon emissions.

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.

This Perspective considers the addition of ACKR1 genetic testing for identifying ACKR1/DARC-associated neutropenia in patients receiving clozapine, recommending eligibility criteria and testing strategies while estimating substantial cost savings for the UK healthcare system and enhancing equitable treatment access.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

The impacts of antimicrobial resistance are unequally distributed and are more severe in lower- and middle-income countries. Here, the authors perform a critical interpretive synthesis of the evidence on intersectional inequities driving antimicrobial resistance and present a conceptual framework of their findings.

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.

Human-driven forest fragmentation could have major impacts on ecosystem functioning. This global analysis shows that the relationship between fragmentation and vegetation resilience in forests may differ depending on bioclimatic region and local environmental conditions.

Results of an early-phase breast cancer prevention trial demonstrate the potential for breast cancer prevention in premenopausal women with anti-progestin therapy by inducing epithelial–stromal remodelling and suppression of luminal progenitors.

Large-scale genome-wide analyses identify hundreds of genetic loci associated with hypothyroidism and thyroid hormone levels, demonstrating the potential of using polygenic risk scores to predict disease onset and progression.

In this double-blind, randomised, crossover trial, a diet rich in fermentable foods was shown to improve the glucose-lowering efficacy of metformin due, at least in part, to changes in gut microbiota composition.

Identifying theranostic compounds for precision medicine remains a difficult task. Here, the authors develop a deep learning-based hybrid human-AI pipeline to integrate and analyse multiple databases and multimodal datasets to establish the Theranostic Genome, which can be used to propose targeted theranostics therapies.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

Identifying genes involved in MYC-driven lymphoma reveals therapeutic vulnerabilities. Here, the authors show by using CRISPR knockout screens in primary cells in vivo that the GATOR1 complex suppresses MYC-driven lymphomagenesis, and that GATOR1-deficient lymphomas are sensitive to mTOR inhibitors.

Long-read chromatin assay reveals (1) a novel class of accessible chromatin regions, (2) accessibility within individual LTR retrotransposons and (3) the relationship between diffuse accessibility, gene body methylation and hAT transposon insertion.

New in vitro data suggest that the new SARS-CoV-2 Omicron variant is likely to escape neutralization by most therapeutic antibodies currently available.

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.

Unlike squalene, peplusol is only synthesized in a few species of the Euporbia genus and its biosynthetic pathway is unclear. Here, the authors report the discovery and characterization of two peplusol synthases and demonstrate the feasibility of the evolution of peplusol synthase from the ancient squalene synthase.

This study correlates the structure and the CO₂ photohydrogenation performance of a series of isostructural Ni-based MOFs. Comparative characterization reveals the occurrence of an in situ restructuring, yielding different surface active sites.

In this study, the authors assess the global response to the toxic aldehyde glyoxal (GO) in Pseudomonas aeruginosa, suggesting that GO controls quorum sensing during infection through a mechanism involving a novel protein, ArqI.

Prior evidence suggested mesenchymal stromal cells (MSCs) required for skeletal formation, maintenance, and repair arise postnatally. Here, the authors show that Hoxa11 lineage-marked cells give rise to all skeletal lineages from embryogenesis through adulthood and are upstream progenitors of LepR- and Osx-lineage MSCs

A study of SARS-CoV-2 variants examining their transmission, infectivity, and potential resistance to therapies provides insights into the biology of the Delta variant and its role in the global pandemic.

Here, the authors have mapped the antibody response of the adeno-associated virus 9 (AAV9) gene therapy vector Zolgensma. AAV9 capsid variants were designed to escape this response while preserving manufacturing and biodistribution properties.

Sequencing wild relatives of millet identifies genes that regulate yield and harvesting traits.

Cardiomyocyte cell cycle arrest is important for mammalian heart maturation, but the process is poorly understood. Here, the authors use exome sequencing to identify compound heterozygous ALMS1mutations associated with cardiomyocyte replication and provide evidence that Alström protein deficiency impairs postnatal cardiomyocyte cell cycle arrest.

How neural stem cells can transition between states of proliferation and quiescence is unclear. Here, the authors identify Lrig1 as a specific marker for the primed quiescent state and demonstrate that Lrig1 maintains cells in a quiescent state via modulation of the EGFR pathway.

Artificial self-assembling systems such as anion receptors or ‘binders’ are largely unexplored for therapeutic applications. Here, the authors report self-assembling trimetallic cryptands containing copper, zinc or manganese that encapsulate a range of anions, are highly toxic to human cancer cell lines and show metal-dependent selectivity towards cancer vs. healthy cells linked to the selective inhibition of multiple kinases.

Here, using human liver chimeric mice, the authors describe perturbation of the diurnal transcriptome and epigenome of human hepatocytes during hepatitis C virus infection, affecting pathways mediating metabolic alterations, fibrosis, and cancer, and further show that the pathways remain affected in patients with advanced liver disease.

Although DDX41 genetic variation occurs in myelodysplastic syndrome and acute myeloid leukemia, the pathogenic mechanisms remained unclear. Here, the authors found DDX41 regulates CLK3-dependent alternative splicing to establish transcript ensembles, while pathogenic variants limit the activity.

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.

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.

Through the use of a novel three-dimensional imaging technique, used in conjunction with a multicolour reporter that allows lineage tracing and cell tracking of entire mammary ducts in vivo, bipotent stem cells are shown to have a central role in both puberty and long-term maintenance; in addition, long-lived luminal progenitor cells with a prominent role in ductal expansion are identified.

Molecular alterations in ctDNA of patients with mantle cell lymphoma uncovers mutations in SWI–SNF associated with resistance to ibrutinib and venetoclax combination and provide a rationale for restoring sensitivity through Bcl-xL inhibition.

Impaired gut barrier function is a central driver of alcohol-related liver disease. This study indicates that the postbiotic ReFerm® improves gut barrier function and reduce liver stiffness and liver fibrosis, suggesting the gut barrier function as a potential treatment target.

The goal of the 1000 Genomes Project is to provide in-depth information on variation in human genome sequences. In the pilot phase reported here, different strategies for genome-wide sequencing, using high-throughput sequencing platforms, were developed and compared. The resulting data set includes more than 95% of the currently accessible variants found in any individual, and can be used to inform association and functional studies.

Neurons receive their input in three dimensions via their dendrites, but how electrical activity in dendrites is organized is unknown. Here, the authors work out the distinct rules that govern activity across this 3D structure in different brain states.

The genome of the model fern species Ceratopteris richardii reveals a history of remarkably dynamic genome evolution, including rapid changes in genome content and structure following the most recent whole-genome duplication approximately 60 million years ago.

The authors use artificial intelligence approaches to explore the predictive value of whole exome sequencing in forecasting clinical outcomes following surgery for congenital heart defects. Findings include that damaging genotypes in chromatin-modifying and cilia-related genes are associated with an increased risk of adverse post-operative outcomes such as mortality, cardiac arrest, and prolonged mechanical ventilation.

Telomere dysfunction induced by TRF1 depletion in fibroblasts, club and basal cells did not lead to interstitial lung fibrosis, underscoring alveolar type II cells as the relevant cell type in pulmonary fibrosis.

The SpyTag/SpyCatcher protein ligation technology is valuable in many applications, but few methods exist for controlling reactivity. Here the authors report a method for controlling SpyCatcher activity via S-thiolation of engineered cysteines, demonstrating the value of their technology for the rapid generation of bispecific antibodies.

This study provides the first evidence in humans that tirzepatide modulates brain electrophysiology, with changes in low-frequency accumbens power linked to food preoccupation.