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Understanding the mechanisms underlying the survival of drug tolerant persister cells following chemotherapy remains elusive. Here, multi-omics analysis and experimental approaches show that the germ-cell-specific H3K4 methyltransferase PRDM9 promotes metabolic rewiring in glioblastoma stem cells.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

Confocal Airy beam integrated with single-photon oblique light-sheet tomography (CAB-OLST) is a high-throughput imaging approach for brain-wide mapping of neurons, as demonstrated in cleared mouse brains.

Here the authors provide an explanation for 95% of examined predicted loss of function variants found in disease-associated haploinsufficient genes in the Genome Aggregation Database (gnomAD), underscoring the power of the presented analysis to minimize false assignments of disease risk.

In the final report of a phase 1 trial evaluating intracerebroventricular B7-H3-targeting CAR T cells in children and young adults with diffuse intrinsic pontine glioma, repeated intracranial infusions were feasible and well tolerated with a median overall survival of 19.8 months and 3 patients surviving over 40 months from diagnosis.

The causative agent of sea star wasting disease has been elusive. This study used genetic datasets and experimental exposures to demonstrate that a strain of the bacterium Vibrio pectenicida caused disease and mortality in sea stars.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

Federated learning (FL) algorithms have emerged as a promising solution to train models for healthcare imaging across institutions while preserving privacy. Here, the authors describe the Federated Tumor Segmentation (FeTS) challenge for the decentralised benchmarking of FL algorithms and evaluation of Healthcare AI algorithm generalizability in real-world cancer imaging datasets.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

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.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

Sequencing data from two large-scale studies show that most of the genetic variation influencing the risk of type 2 diabetes involves common alleles and is found in regions previously identified by genome-wide association studies, clarifying the genetic architecture of this disease.

Genomic studies often lack representation from diverse populations, limiting equitable insights. Here, the authors show that the BIG Initiative captures extensive genetic diversity and reveals ancestry-linked health disparities in a community-based Mid-South cohort.

Multiple observational datasets and reconstructions using data from tree rings confirm that human activities were probably affecting the worldwide risk of droughts as early as at the beginning of the twentieth century.

The authors analyze rare coding variants in 1990 individuals with congenital kidney anomalies, finding diagnostic variants in 14.1% of cases. They identify two new causal genes, ARID3A and NR6A1, along with 38 candidate genes, providing evidence for shared genetics with other developmental disorders.

Exome-sequencing analyses of a large cohort of patients with type 2 diabetes and control individuals without diabetes from five ancestries are used to identify gene-level associations of rare variants that are associated with type 2 diabetes.

Palmer et al. present interim findings from their clinical trial; they describe the reactogenicity and immunogenicity results of a self-amplifying mRNA SARS-CoV-2 booster vaccine within an older population (≥60 years of age).

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

The influence of climate on premodern civil conflict and societal instability is debated. Here, the authors combine archeological, historical, and paleoclimatic datasets to show that drought between 1400-1450 cal. CE escalated civil conflict at Mayapan, the largest Postclassic Maya capital of the Yucatán Peninsula.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

A study that tracked mammal populations before, during and after a severe storm in Mozambique’s Gorongosa National Park finds that behavioural responses and survival are linked to body size, with increased mortality of small species owing to limited mobility and changes in food availability.

Different functional variants in ADH1B (and elsewhere) in Europeans and Africans strongly affect risk for alcohol dependence. Dependence only partly genetically correlates with consumption, with strong correlations to other psychiatric disorders.

Genotype and exome sequencing of 150,000 participants and whole-genome sequencing of 9,950 selected individuals recruited into the Mexico City Prospective Study constitute a valuable, publicly available resource of non-European sequencing data.

Exceptionally wet growing seasons, compared to the past 700 years, preceded the European Great Famine of 1315-1317 and are associated with a newly identified hydroclimate pattern, according to analyses of Europe-wide tree ring data.

Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.

After infection with SARS-CoV-2 a diverse set of symptoms remain or develop longer term in a condition termed long-CoVID, yet an accurate and tractable model has remained elusive. Here the authors present a non-human primate model of long-CoVID and show persistent hyperglycemia following acute infection.

Multi-modal analysis is used to generate a 3D atlas of the upper limb area of the mouse primary motor cortex, providing a framework for future studies of motor control circuitry.

Cold ENSO states can lead to the simultaneous occurrence of megadroughts in southwestern North and South America, according to a hydroclimate reconstruction of the last thousand years assimilating palaeoclimate records with climate model constraints.

Federated ML (FL) provides an alternative to train accurate and generalizable ML models, by only sharing numerical model updates. Here, the authors present the largest FL study to-date to generate an automatic tumor boundary detector for glioblastoma.

A dataset of coding variation, derived from exome sequencing of nearly one million individuals from a range of ancestries, provides insight into rare variants and could accelerate the discovery of disease-associated genes and advance precision medicine efforts.

Kyle Gaulton, Mark McCarthy, Andrew Morris and colleagues report fine mapping and genomic annotation of 39 established type 2 diabetes susceptibility loci. They find that the set of potential causal variants is enriched for overlap with FOXA2 binding sites in human islet and liver cells, and they show that a likely causal variant near MTNR1B increases FOXA2-bound enhancer activity, providing a molecular mechanism to explain the effect of this locus on disease risk.

The genome of the Antarctic blackfin icefish shows expansion of genes involved in protection from damage caused by ice and high-oxygen concentrations, which reflects adaptation to extreme Antarctic environments.

Megadroughts can be defined as persistent, multi-year droughts that are exceptional compared with other regional events during the Common Era. This Review discusses palaeo reconstructions of megadroughts over the past 2,000 years, and outlines the impact of anthropogenic forcing on the severity and frequency of observed and projected events.

Penetrance of variants in monogenic disease and clinical utility of common polygenic variation has not been well explored on a large-scale. Here, the authors use exome sequencing data from 77,184 individuals to generate penetrance estimates and assess the utility of polygenic variation in risk prediction of monogenic variants.

An exome-wide association study of six smoking phenotypes in up to 749,459 individuals identifies associations of rare coding variants in CHRNB2 that may reduce the likelihood of smoking.

Combining 32 genome-wide association studies with high-density imputation provides a comprehensive view of the genetic contribution to type 2 diabetes in individuals of European ancestry with respect to locus discovery, causal-variant resolution, and mechanistic insight.

A genetic study identifies hundreds of loci associated with risk tolerance and risky behaviors, finds evidence of substantial shared genetic influences across these phenotypes, and implicates genes involved in neurotransmission.

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.

Circulating tumour DNA profiling in early-stage non-small-cell lung cancer can be used to track single-nucleotide variants in plasma to predict lung cancer relapse and identify tumour subclones involved in the metastatic process.

A six-letter sequencing workflow can simultaneously detect genetic and epigenetic bases.

Whole-ecosystem manipulations of Caribbean islands occupied by brown anoles, involving the addition of competitors (green anoles) and/or top predators (curly-tailed lizards), demonstrate that predator introductions can alter the ecological niches and destabilize the coexistence of competing prey species.

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

Study shows that proposed carbon nanotube cables won't hold up.

Protein immunofluorescence imaging and affinity purification–mass spectrometry are combined to create a unified map of human cell architecture across scales, which the authors call the multi-scale integrated cell (MuSIC).