Search

Sarcoma is a highly heterogeneous disease, which can be caused by a large variety of mutations. Here, the authors utilise multi-omics to characterise a cohort of 1,340 sarcoma tissue specimens to identify key somatic mutations and identify immune subtypes.

The role of IgG glycosylation in the immune response has been studied, but less is known about IgM glycosylation. Here the authors characterize glycosylation of SARS-CoV-2 spike specific IgM and show that it correlates with COVID-19 severity and affects complement deposition.

Combined patch clamp recording, biocytin staining and single-cell RNA-sequencing of human neurocortical neurons shows an expansion of glutamatergic neuron types relative to mouse that characterizes the greater complexity of the human neocortex.

Maize originated in southern Mexico from domestication of the wild grass teosinte, and diffused throughout the Americas. Sequenced DNA from archaeological samples spanning 6,000 years, documents the diffusion route and reveals the genes that were specifically selected for climatic and cultural adaptation to the US Southwest.

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.

Transcranial alternating current stimulation (TACS) of the brain is widely used in neuroscience, but the electric fields produced when multiple stimulation electrodes are used are not well understood. Here, the authors directly record electric fields in primate brains during multi-electrode TACS.

“Dissolved oxygen (DO) sustains river ecosystems, but the effects of hydrological extremes remain poorly understood. Here it is shown that sudden floods cause abrupt declines in DO, suggesting that increased future flooding may lead to the degradation of aquatic ecosystems.

This work presents a computationally efficient approach to establish spatially fine-grained connectivity gradients, reducing computational costs while preserving informative individual features and improving brain-behavior predictions.

Biomolecules morph between conformations with distinct lifetimes essential for function. This study reveals the cores of flaviviral RNAs stay stable up to ten million times longer than canonical base pairs to effectively resist exonuclease digestion.

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.

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

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.

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.

Ultrack leverages candidate segmentations from multiple algorithms and temporal consistency across time points for robust, long-term 3D segmentation in challenging samples such as densely packed zebrafish, fruit fly and nematode embryos.

Metformin may serve as a non-toxic intervention to inhibit mitochondrial metabolism and slow DNMT3A-R882 clonal haematopoiesis expansion, thus delaying or averting progression to acute myeloid leukaemia.

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.

Despite the importance of osteoclast secretory lysosomes in bone digestion, the proteins that regulate them remain ill defined. Here, the authors identify Slc37a2 as a secretory lysosome sugar transporter that is required for maintenance of skeletal bone mass.

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.

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.

The response to infectious and inflammatory challenges differs among people but the reasons for this are poorly understood. Here the authors explore the impact of variables such as age, sex, and the capacity for controlling inflammation and maintaining immunocompetence, linking this capacity to favourable health outcomes and lifespan.

The relevance of mitochondrial cysteine metabolism to ferroptosis is unknown. Here, Ward et al. show that mitochondrial Fe-S cluster synthesis persists under cysteine limitation via the catabolism of glutathione and at the expense of cell viability.

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.

Mutations in the splicing factor RBM20 cause aggressive Dilated Cardiomyopathy. Here the authors generated RBM20 R636S mutants and knockout in human iPSC-derived cardiomyocytes. Mutant RBM20 showed different target RNA binding, altered splicing and localization to cytoplasmic processing bodies.

Glutathione has pleiotropic functions in different organs. Here the authors specifically examine deletion of a glutathione synthetic enzyme in the liver of adult mice and show that lack of glutathione affects lipid abundance through repressing NRF2.

Corticosteroid therapy is frequently used for chronic obstructive pulmonary disease (COPD) but its use is associated with increased risk of pneumonia. Here the authors show that corticosteroid use impairs innate and adaptive immunity to rhinovirus infection, which is restored by exogenous IFNβ.

The formation of large-scale brain networks represents crucial developmental processes that can drive individual differences in cognition and which are associated with multiple neurodevelopmental conditions. Here, the authors use generative network modelling to provide a computational framework for understanding neurodevelopmental diversity.

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.

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.

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.

Solid organ transplant recipients are at increased risk of infectious disease and have unique molecular pathophysiology. Here the authors use host-microbe profiling to assess SARS-CoV-2 infection and immunity in solid organ transplant recipients, showing enhanced viral abundance, impaired clearance, and increased expression of innate immunity genes.

Alzheimer’s disease has been associated with increased structural brain aging. Here the authors describe a model that predicts brain aging from resting state functional connectivity data, and demonstrate this is accelerated in individuals with pre-clinical familial Alzheimer’s disease.

The United States is one of the largest soybean exporters in the world. An analysis of meteorological and field-trial data spanning the past 20 years suggests that climatic changes have reduced US soybean yields by around 30%.

In this study, the authors provide a global overview of SARS-CoV-2 genome sequencing, and estimate the proportion of cases sequenced and time to genome upload. They identify disparities and highlight the need to strengthen surveillance in lower and middle income countries.

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.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

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.

A study finds that a protease called granzyme K can activate the entire complement cascade, explaining how it can drive destructive inflammation in inflammatory diseases such as rheumatoid arthritis.

Shen et al. report a method for multiplexing isogenic iPSCs for single-cell RNA-seq. With it, they created an atlas of in vitro differentiation and identified TMEM88 as a regulator of cardiovascular development, impacting blood pressure in adult mice.

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.

Mutations in the NRF2-KEAP1 pathway is found to be related with therapeutic resistance and poor outcomes of non-small cell lung cancer (NSCLC). Here this group reports that cystine/glutamate antiporter system xc−, controlled by NRF2, can be non-invasively imaged by positron emission tomography thereby providing a sensitive and specific marker of NRF2 activation in advanced preclinical models of NSCLC.

The chaperone Hsp90 uses the free energy from ATP hydrolysis to control the folding of client proteins in eukaryotic cells. Here the authors provide mechanistic insights into how its catalytic activity is coupled to conformational changes by combining large-scale molecular simulations with NMR, FRET and SAXS experiments.