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

Genome-wide association analyses identify new risk loci for heart failure and its subtypes, extending understanding of the underlying biological pathways and disease mechanisms.

Analyses of the TRACERx study unveil the relationship between tissue morphology, the underlying evolutionary genomic landscape, and clinical and anatomical relapse risk of lung adenocarcinomas.

Despite the identification of genetic risk loci for late-onset Alzheimer’s disease (LOAD), the genetic architecture and prediction remains unclear. Here, the authors use genetic risk scores for prediction of LOAD across three datasets and show evidence suggesting oligogenic variant architecture for this disease.

A cross-ancestry meta-analysis of genome-wide association studies identifies association signals for stroke and its subtypes at 89 (61 new) independent loci, reveals putative causal genes, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as potential drug targets, and provides cross-ancestry integrative risk prediction.

It is uncertain how much life expectancy of the Chinese population would improve under current and greater policy targets on lifestyle-based risk factors for chronic diseases and mortality behaviours. Here we report a simulation of how improvements in four risk factors, namely smoking, alcohol use, physical activity and diet, could affect mortality. We show that in the ideal scenario, that is, all people who currently smokers quit smoking, excessive alcohol userswas reduced to moderate intake, people under 65 increased moderate physical activity by one hour and those aged 65 and older increased by half an hour per day, and all participants ate 200 g more fresh fruits and 50 g more fish/seafood per day, life expectancy at age 30 would increase by 4.83 and 5.39 years for men and women, respectively. In a more moderate risk reduction scenario referred to as the practical scenario, where improvements in each lifestyle factor were approximately halved, the gains in life expectancy at age 30 could be half those of the ideal scenario. However, the validity of these estimates in practise may be influenced by population-wide adherence to lifestyle recommendations. Our findings suggest that the current policy targets set by the Healthy China Initiative could be adjusted dynamically, and a greater increase in life expectancy would be achieved.

Tree mortality has been shown to be the dominant control on carbon storage in Amazon forests, but little is known of how and why Amazon forest trees die. Here the authors analyse a large Amazon-wide dataset, finding that fast-growing species face greater mortality risk, but that slower-growing individuals within a species are more likely to die, regardless of size.

Petroni et al. report that the infiltration of IL-17A-secreting γδ T cells in the tumor microenvironment coupled with the accumulation of immunosuppressive macrophages is associated with resistance to CDK4/CDK6 inhibition in HR⁺HER2⁻ breast cancer.

Integrative analysis in patients with diffuse large B-cell lymphoma uncovers that biallelic mutations on TMEM30A are associated with a favorable outcome and enhanced sensitivity to CD47 blockade.

A region on chromosome 19p13 is associated with the risk of developing ovarian and breast cancer. Here, the authors genotyped SNPs in this region in thousands of breast and ovarian cancer patients and identified SNPs associated with three genes, which were analysed with functional studies.

A barcode-based approach applied to UK Biobank and an Icelandic cohort identifies drivers of clonal hematopoiesis (CH) and finds associations between CH and multiple diseases. Genome-wide association analyses identify 25 loci associated with CH susceptibility.

Simon and colleagues show that liver cancer cells undergo cell cycle arrest and senescence upon deprivation of methionine and identify GSK3 inhibitors as a senolytic to selectively deplete MAT2A inhibited senescent liver cancer cells.

Hundreds of genetic loci associated with age at menopause, combined with experimental evidence in mice, highlight mechanisms of reproductive ageing across the lifespan.

Chemotherapy causes changes to immune infiltration and activation in high grade serous ovarian cancer patients. Here, the authors use single cell RNA-seq to identify key markers differentially expressed on macrophages and Treg cell types following treatment which may affect treatment response.

Identifying biomarkers associated with risk of severe COVID-19 disease could inform clinical management. Here, the authors identify a long noncoding RNA associated with severe disease using data from three European countries, and validate their finding in data from Canada.

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.

The enzyme ABHD18 is shown to have a key role in cardiolipin metabolism in mitochondria, offering a potential route for a small-molecule treatment of the rare genetic disease Barth syndrome.

Fine-mapping of causal variants and integration of epigenetic and chromatin conformation data identify likely target genes for 150 breast cancer risk regions.

Combination of epidemiology, preclinical models and ultradeep DNA profiling of clinical cohorts unpicks the inflammatory mechanism by which air pollution promotes lung cancer

Artificial Intelligence (AI) has the potential of assisting the study and diagnosis of veterinary cancers. Here, the authors build a cancer digital pathology atlas encompassing multiple animal species and demonstrate an AI approach for comparative pathology, which yields insights about immune response and morphological similarities.

A genome-wide study by the Long COVID Host Genetics Initiative identifies an association between the FOXP4 locus and long COVID, implicating altered lung function in its pathophysiology.

The heparan sulfate proteoglycan-binding cytokine APRIL has a protective role against atherosclerotic disease.

Understanding the molecular mechanisms of cancer immunoediting could provide insight into resistance to immunotherapy. Here, DNA barcoding provides evidence of ongoing immunoediting during metastasis and treatment with anti-PD1 and anti-CTLA4, and identifies cancer cell clones with unique immune evasive phenotypes.

Genome-wide analyses identify variants associated with sinus node dysfunction, distal conduction disease and pacemaker implantation, implicating ion channel function, cardiac developmental programs and sarcomeric structure in bradyarrhythmia susceptibility.

Understanding the growth dynamics of GBMs can help expand therapeutic options. Here, authors use a cross-species computational approach to compare GBM cells to healthy neural stem cells, identifying predictors and modulators of tumour growth, including the Wnt antagonist, SFRP1, which stalls growth in preclinical xenograft models.

A CRISPR knock-in strategy that uses endogenous gene regulatory mechanisms can engineer ‘armoured’ CAR T cells that secrete proinflammatory cytokines directly within a tumour without causing toxicity, leading to prolonged survival in mice.

Using a natural experiment that avoids common bias concerns, this study finds that the live-attenuated shingles vaccine reduced the probability of a new dementia diagnosis within a follow-up period of 7 years by approximately one-fifth.

α/β-hydrolase domain-containing protein 11 (ABHD11) is a mitochondrial hydrolase, and its expression in CD4 + T-cells has been linked to remission status in rheumatoid arthritis. Here the authors report that pharmacological inhibition of ABHD11 modulates T-cell effector function via increased 24,25-epoxycholesterol biosynthesis and subsequent liver X receptor activation.

A single MRI scan can provide reliable estimates of human lifetime brain atrophy, helping overcome lifespan data collection challenges. This may enhance genetic studies of late-life neurodegeneration and reveal new insights into its underlying mechanisms.

In breast cancer the contribution of different genetic variants to disease heritability is complex and not fully understood. Here, the authors present a network-based analysis in 84,567 patients studying ~7.3 million variants, identifying gene modules associated with breast cancer survival.

The spatial architecture of multiple myeloma remains to be explored. Here, the authors perform bulk and single cell sequencing for samples from newly diagnosed patients and reveal gene signatures associated with focal lesions and spatial heterogeneity in the tumour microenvironment.

Joint analysis of new and previously published sequencing data for primary and metastatic prostate cancers identifies new candidate driver mutations and provides insights into disease progression and potential drug targets.

The ability to oxidise hydrocarbons aerobically has been described in bacteria but not yet in archaea. Here, Leu et al. analyse metagenomic datasets from various environments and provide evidence supporting potential aerobic hydrocarbon oxidation ability in an archaeal lineage within the class Syntropharchaeia.

Combining the kinase inhibitor sorafenib with allogeneic stem cell transplantation boosts immune responses against a subtype of acute myelogenous leukemia, suggesting potential clinical benefit.

Although vaccination drops COVID-19 mortality in older adults, post-vaccine fatal COVID-19 in nursing home outbreaks was linked to Delta, Gamma and Mu variants, persistently detected in aerosols. Mortality was predicted by IFNB1 or age, ORF7a and ACE2 mRNAs.

Trained on large and multicenter datasets with different imaging modalities, a foundation model is shown to have strong performance on the full spectrum of clinically relevant tasks and to increase user accuracy in diagnostic tasks.

Kverneng et al. assess the mitochondrial respiratory chain in skeletal muscle from persons with Parkinson’s disease. Their findings suggest the existence of a subpopulation with complex I deficiency and support the potential of extra-neural biomarkers for patient stratification.

Proteomics can be used to refine cancer classification. Here, the authors characterise chronic lymphocytic leukaemia patients by proteogenomics, and identified a subtype of patients with poor prognosis associated with aberrant B cell receptor signalling.

The onset and pathology of Alzheimer’s disease (AD) is associated with changes to lipid metabolism. Here, the authors analysed 569 lipids from 32 classes and subclasses in two independent patient cohorts to identify key lipid pathways to link the plasma lipidome with AD and the future onset of AD.

MPHOSPH8 loss inhibits acute myeloid leukemia (AML) development by reactivating LINE-1 retrotransposons. LINE-1 suppression is associated with therapy resistance and poor prognosis in patients with AML.

Lipoxins and aspirin-triggered lipoxins have emerged as important factors in anti-inflammatory and proresolution pathways, the absence of which might cause chronic inflammation. The newly discovered resolvins and protectins, derived from omega-3 polyunsaturated fatty acids, are also potent locally acting agonists of endogenous anti-inflammation, and promote resolution. The functions of these lipid mediators, and their potential beneficial use in rheumatoid arthritis, are outlined in this Review.

Right-sided colorectal cancer (rCRC) has a different mutational spectrum to the left-sided counterpart. Here the authors develop a mouse model of rCRC that recapitulates human BRAF-mutant rCRC and show that loss of TGFβ-receptor signalling and inflammation induce the development of colonic tumours with a foetal-like phenotype.

Structural classification of mutations in the epidermal growth factor receptor causing non-small cell lung cancer is a better predictor of patient outcomes following drug treatment than traditional exon-based classification.

Alison Dunning, Stacey Edwards and colleagues analyze 3,872 common variants across the ESR1 locus in 118,816 women. They find five independent variants within regulatory regions that associate with different breast cancer–related phenotypes and regulate the expression of ESR1, RMND1 and CCDC170.

Existing clinical models cannot fully capture smoldering multiple myeloma (SMM) heterogeneity. Here, integration of 42 genetic alterations from 214 SMM patients using an unsupervised binary matrix factorization clustering approach results in the identification of 6 distinct molecular and clinical subtypes.