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SARS-CoV-2 challenge of rhesus macaques demonstrates that the Ad26.COV2.S vaccine induces robust protection against both the WA1/2020 isolate and the B.1.351 variant of concern.

Here, the authors conduct a paired genome analysis of humans and Mycobacterium tuberculosis in a cohort from Lima, Peru. Their research reveals that genetic variations in both the host and pathogen significantly influence the progression to tuberculosis.

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.

Overfeeding triggers a mechanistically ill-defined compensatory response that counteracts weight gain. Here, the authors show that the defence against overfeeding is preserved in obesity, and that it is independent from FGF21 and MC4R.

Results for the final phase of the 1000 Genomes Project are presented including whole-genome sequencing, targeted exome sequencing, and genotyping on high-density SNP arrays for 2,504 individuals across 26 populations, providing a global reference data set to support biomedical genetics.

Stratified medicine promises to tailor treatment for individual patients, however it remains a major challenge to leverage genetic risk data to aid patient stratification. Here the authors introduce an approach to stratify individuals based on the aggregated impact of their genetic risk factor profiles on tissue-specific gene expression levels, and highlight its ability to identify biologically meaningful and clinically actionable patient subgroups, supporting the notion of different patient ‘biotypes’ characterized by partially distinct disease mechanisms.

Wolbachia bacteria live within the cells of many insects, including the mosquito Culex pipiens. Here, the authors analyse new and existing Wolbachia metagenomes from C. pipiens mosquitoes and find evidence of a plasmid, which may facilitate genetic manipulation of these bacteria for vector control applications.

Platelet aggregation is associated with myocardial infarction and stroke. Here, the authors have conducted a whole genome sequencing association study on platelet aggregation, discovering a locus in RGS18, where enhancer assays suggest an effect on activity of haematopoeitic lineage transcription factors.

A genome-wide association study in ~3 million individuals identifies 3,952 independent variants associated with educational attainment. A polygenic index explains 12–16% of variance for this trait and contributes to risk prediction for ten diseases.

Pooling participant-level genetic data into a single analysis can result in variance stratification, reducing statistical performance. Here, the authors develop variant-specific inflation factors to assess variance stratification and apply this to pooled individual-level data from whole genome sequencing.

An improved, fully re-annotated Aedes aegypti genome assembly (AaegL5) provides insights into the sex-determining M locus, chemosensory systems that help mosquitoes to hunt humans and loci involved in insecticide resistance and will help to generate intervention strategies to fight this deadly disease vector.

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.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

For many neurodevelopmental disorder (NDD) risk genes, the significance for mutational burden is unestablished. Here, the authors sequence 125 candidate NDD genes in over 16,000 NDD cases; case-control mutational burden analysis identifies 48 genes with a significant burden of severe ultra-rare mutations.

The genetic basis of atopic dermatitis is not fully understood. Here, the authors find 91 genetic loci associated with atopic dermatitis in a GWAS of >1million individuals, which highlight the importance of systemic immune regulation.

Tools for cardiac physiological mapping are important for basic and clinical cardiac research. Here the authors use 3D printing to create a thin, elastic silicone sheath that fits tightly around the entire epicardium and contains sensors to measure a variety of physiological parameters of the beating heart ex vivo.

Even as new treatments loom, researchers are still trying to understand what goes wrong inside the cells of people with the genetic disorder.

A high proportion of confirmed SARS-CoV-2 cases in Denmark were sequenced during the pandemic and linked to demographic, spatial and temporal data. Here, the authors analyse 290,000 genomes sampled in 2021 to demonstrate the value of this high coverage, detailed data set.

The epigenomic landscape of renal cell carcinoma (RCC) remains to be explored. Here, integrative epigenomic analysis of primary human RCC samples and RCC GWAS risk SNPs identifies transcription-factor specific subtypes and enrichment of risk variants in allelically-imbalanced peaks.

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.

Pipercevic et al resolve how inositol molecules activate the VTC protein complex. The VTC complex stores phosphate in yeast and is controlled by SPX domains. The inositol molecules break an interaction between SPX domains to activate the complex.

Here the authors used cryogenic electron microscopy and biochemistry to understand how yeast Mcm10 exerts its essential role in DNA replication initiation, finding that it splits the double Cdc45-MCM-GINS-Polε structure. The lagging-strand template is ejected from each MCM ring as the central channel of the helicase becomes too tight to accommodate two DNA strands.

While many treatments for prostate cancer suppress the androgen receptor it becomes reactivated during disease progression. Here, the authors show that a KLF5 transcriptional programme is also activated during treatment and promotes migration and the appearance of a basal cell phenotype.

Insulin resistance is emerging as an early metabolic risk marker in youth with mood disorders. In this Comment, we examine the interplay of insulin resistance, inflammation and circadian disruption that worsens both metabolic symptoms and mood symptoms, highlighting the potential for early integrated interventions.

Transmission spectroscopy observations from the James Webb Space Telescope show the detection of carbon dioxide in the atmosphere of the gas giant exoplanet WASP-39b.

This Resource presents the genetic subset of the 136,000 chemical and genetic perturbations tested by the Joint Undertaking for Morphological Profiling (JUMP) Cell Painting Consortium and associated analysis of phenotypic profiles.

Fine-scale geospatial mapping of overweight and wasting (two components of the double burden of malnutrition) in 105 LMICs shows that overweight has increased from 5.2% in 2000 to 6.0% in children under 5 in 2017. Although overall wasting decreased over the same period, most countries are not on track to meet the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025.

Alzheimer’s Disease (AD) is commonly preceded by a prodromal period. Here, the authors report the presence of large plasma Aβ aggregates from patients with mild cognitive impairment, which associate with low level AD-like brain pathology as observed by 11C-PiB PET and 18F-FTP PET and lowered CD18-rich monocytes.

A blood-based DNA sequencing assay to infer tumor mutational burden in the absence of tumor biopsy predicts response to PD-L1 blockade in patients with non-small-cell lung cancer.

Surfactant protein B (SP-B) deficiency is a genetic lung disease that results in lethal respiratory distress within months of birth. Here, the authors describe a gene therapy strategy using a rationally designed AAV6 capsid that restores surfactant homeostasis, prevents lung injury, and improves survival in a mouse model of SP-B deficiency.

Kohlmeier and colleagues showed that the airway environment drove transcriptional and epigenetic changes that regulated the cytolytic functions of airway T_RM cells and promoted their apoptosis due to amino acid starvation and activation of the integrated stress response.

Sarcomatoid and rhabdoid tumours are highly aggressive forms of renal cell carcinoma that are also responsive to immunotherapy. In this study, the authors perform a comprehensive molecular characterization of these tumours discovering an enrichment of specific alterations and an inflamed phenotype.

Swarm Learning is a decentralized machine learning approach that outperforms classifiers developed at individual sites for COVID-19 and other diseases while preserving confidentiality and privacy.

The burden of mosaic chromosomal alterations in blood-derived DNA, a type of clonal hematopoiesis, is associated with an increased risk for diverse types of infections, including sepsis and pneumonia.

The molecular processes that lead to neuroendocrine prostate cancer after treating prostate adenocarcinoma (PRAD) are not well understood. Here the authors show that regulation by FOXA1 and changes in the epigenomic profile drive the transition from PRAD to a neuroendocrine phenotype.

Human:pig embryos can be produced by deleting the MYF5, MYOD and MYF6 genes in pig embryos via CRISPR and somatic-cell nuclear transfer, followed by the delivery of TP53-null human induced pluripotent stem cells via blastocyst complementation.

Advanced paternal age associates with increased risk for psychiatric and developmental disorders in offspring. Here, Taylor et al. utilize parent-child trio exome sequencing data sets to estimate the contribution of paternal age-related de novo mutations to multiple disorders, including heart disease and schizophrenia.

HLA peptidomic analysis identifies recurrent intracellular bacteria-derived peptides presented on HLA-I and HLA-II molecules in melanoma tumours, revealing how bacteria can modulate immune functions and responses to cancer therapies.

The Alpha variant of SARS-CoV-2 outcompetes progenitor SARS-CoV-2 in upper respiratory tract replication competition in vivo.

Systematic characterization of longitudinal tau variability in human Alzheimer’s disease using an unbiased subtyping algorithm reveals four trajectories of tau deposition with distinct clinical features.

Here the authors demonstrate the active control of an all-optical switch harnessing the interaction of light with the constituent materials. The response speeds up by two orders of magnitude and scales accordingly with the strength of the light matter interaction.

As phase 1 of the Earth Microbiome Project, analysis of 16S ribosomal RNA sequences from more than 27,000 environmental samples delivers a global picture of the basic structure and drivers of microbial distribution.

The use of functional genomics in primary immune cells has been limited by inefficient vector delivery and risk of perturbing cell states. Here the authors present CHimeric IMmune Editing (CHIME) for in vivo evaluation of gene function and pooled screening approaches.

Physical distancing during COVID-19 was more difficult for residents of low-income US neighbourhoods. Using smartphone mobility data, Jay et al. find that days at work, not visits to other locations, explain these disparities and that state policies did not correct them.

In the US, 99.8% of the 459 endangered animals are susceptible to at least one climate change sensitivity factor. Yet analysis of official documents (1973–2018) shows this risk does not translate into action: only 64% of species are considered threatened by climate change, and management planned for 18%.

Sequencing a human genome using next-generation methods does not distinguish between the two copies of each chromosome. Kitzman et al. determine a haplotype-resolved genome sequence by efficiently constructing and sequencing long-insert clones that cover the diploid genome with a low likelihood of overlap.