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For years, manufacturers have used one of only two chemicals to inactivate viruses for vaccine production: formaldehyde or β-propiolactone, and formaldehyde can damage key antigenic epitopes, leading to reduced immunogenicity or exacerbated disease. Ian Amanna and his colleagues have now found a third, the oxidizing agent hydrogen peroxide (H₂O₂), which they show can be more effective than the conventional approaches. Utility of the H₂O₂-based approach is demonstrated in three model systems.

To overcome limitations of previous genome-wide association studies of coronary artery disease, this study incorporates a cohort of individuals containing large fractions of Black and Hispanic individuals to provide a wider view of the genetic landscape of this disease.

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 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

A study describes the metabolic adaptations supporting differentiation, survival and function of tissue-resident memory CD8⁺ T cells and how to leverage them to enhance immunity against pathogens and tumours.

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 flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

Understanding how palladium inhibits CO poisoning is important for rational design of enhanced catalysts. Here the authors show high formate coverage on the palladium-modified electrode inhibits poisoning during formic acid oxidation and the adsorption of CO precursor dictates the delayed poisoning during CO2 reduction.

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.

Exhausted T cells arise when chronic activation triggers functional defects. Here the authors show that chronic antigenic stimulation in both tumour and infection models induces the expression of EGR2, which drives and stabilises exhausted cell epigenetic and transcriptional identity.

Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.

A genome-wide association study in more than 400,000 individuals identifies 139 new signals for lung function. These variants can predict chronic obstructive pulmonary disease in independent, transancestral cohorts.

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

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 authors measured the variability of neuronal responses across a large number of datasets and cortical areas. They found that variability decreased in response to all stimuli tested, whether the animal was awake, behaving or anesthetized, suggesting that the stabilization of cortex in response to an input is a general cortical property.

Fernando Rivadeneira and colleagues in the Genetic Factors for Osteoporosis Consortium report a large-scale meta-analysis identifying new loci associated with bone mineral density (BMD) and risk of fracture. Thirty-two new loci are found to be associated with BMD, and 6 loci confer higher risk for low-trauma bone fracture.

The relative importance of the mechanisms underlying species radiation remains unclear. Here, the authors combine reference genome assembly and population genetics analyses to show that neutral forces have contributed to the radiation of the most species-rich tree genus Syzygium.

An investigation using various methods reports an association between adeno-associated virus 2 and paediatric hepatitis of unknown aetiology.

Data from over 700,000 individuals reveal the identity of 83 sequence variants that affect human height, implicating new candidate genes and pathways as being involved in growth.

Belz and colleagues show that GFI1, a transcriptional repressor that recruits histone-modifying enzymes, is necessary for the generation and maintenance of stem cell memory CD8⁺ T cells.

A dataset of the genomes of 363 species from the Bird 10,000 Genomes Project shows increased power to detect shared and lineage-specific variation, demonstrating the importance of phylogenetically diverse taxon sampling in whole-genome sequencing.

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.

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.

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.

In this study, the authors show that the mouse ortholog of the amyotropic lateral sclerosis/frontotemporal dementia (ALS/FTD)-associated human locus C9ORF72 exhibits highly enriched expression in the neuronal cell types that show susceptibility during the disease. These findings suggest a potential explanation for the cell selectivity observed in ALS/FTD.

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.

Alex Kentsis and colleagues identify somatic genomic rearrangements in primary human rhabdoid tumors characterized by deletions and inversions involving PGBD5-specific signal sequences at their breakpoints. They further show that ectopic expression of PGBD5 in primary immortalized human cells is sufficient to promote cell transformation in vitro and in immunodeficient mice in vivo, thus defining PGBD5 as an oncogenic mutator and providing a plausible mechanism for site-specific DNA rearrangements in solid tumors.

White matter hyperintensities (WMH) are a common brain-imaging feature of cerebral small vessel disease. Here, the authors carry out a GWAS and followup analyses for WMH-volume, implicating several variants with potential for risk stratification and drug targeting.

Exome-wide analysis identifies rare and low-frequency coding variants associated with body mass index. Gene-based meta-analysis and functional studies implicate 13 genes, eight of which are novel, and neuronal pathways as factors in human obesity.

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.

The development of IDH variant inhibitors is a breakthrough as it is the first time metabolism has been successfully targeted by small molecule drugs in cancer. Here the authors report studies on resistance to the pioneer drug ivosidenib leading to identification of inhibitors retaining activity.

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.

The characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet-base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.

Sequence assemblies for the genomes of 16 widely used inbred laboratory mouse strains highlight considerable strain-specific haplotype variation and allow for the identification of regions with the greatest sequence diversity between strains.

The Progressive Cactus program can create reference-free alignments of hundreds of large vertebrate genomes efficiently, and is used for the alignment of more than 600 amniote genomes.

The Transiting Exoplanet Survey Satellite (TESS) has identified a nearby, bright, quiescent M dwarf star that hosts two sub-Neptune-sized planets and one super-Earth-sized planet. The system is eminently suitable for follow-up studies of transit timing variations, radial velocity measurements and transmission spectroscopy.

Genomic analyses of large population-based cohorts uncover the genetic determinants of perivascular space burden, an MRI marker of cerebral small vessel disease, across the lifespan, and reveal potential pathways implicated in the etiology of stroke and dementia.

Genome-wide analysis identifies variants associated with the volume of seven different subcortical brain regions defined by magnetic resonance imaging. Implicated genes are involved in neurodevelopmental and synaptic signaling pathways.

Advances in protein structure prediction have led to a significant influx of protein structure data. Here the authors exploit this data to offer an unbiased overview of complex sequence-structure-function relationships in the protein universe. This work opens up new uses for 3D structure data repositories in meta-omics and other fields of biology.

Observations of TOI-849b reveal a radius smaller than Neptune’s but a large mass of about 40 Earth masses, indicating that the planet is the remnant core of a gas giant.

Mutations in gene pmrB are found in Pseudomonas aeruginosa isolates from cystic fibrosis patients. Here, Bricio-Moreno et al. show in a mouse model of respiratory infection that the mutations enhance bacterial adherence to epithelial cells and resistance to lysozyme, but also increase antibiotic susceptibility.

This study describes the integrative analysis of 111 reference human epigenomes, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression; the results annotate candidate regulatory elements in diverse tissues and cell types, their candidate regulators, and the set of human traits for which they show genetic variant enrichment, providing a resource for interpreting the molecular basis of human disease.