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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).

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.

Analysis of soundscape data from 139 globally distributed sites reveals that sounds of biological origin exhibit predictable rhythms depending on location and season, whereas sounds of anthropogenic origin are less predictable. Comparisons between paired urban–rural sites show that urban green spaces are noisier and dominated by sounds of technological origin.

This study uses gene expression predictors for the dorsolateral prefrontal cortex and other brain regions to perform a transcriptomic imputation analysis of schizophrenia, identifying 413 genic associations across 13 brain regions and 36 significantly enriched pathways.

High-depth sequencing of non-cancerous tissue from patients with metastatic cancer reveals single-base mutational signatures of alcohol, smoking and cancer treatments, and reveals how exogenous factors, including cancer therapies, affect somatic cell evolution.

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.

Laser-based time transfer with near quantum-limited acquisition and timing is demonstrated that can support femtosecond precision over 102 dB link loss, more than sufficient for future time transfer to geosynchronous orbits for future optical clock networks.

From 2003 to 2020, the efficiency of white light-emitting diodes rose from 6% to 39%, while costs fell by 96%. Weinold et al. explore the drivers of such rapid progress to formulate lessons for future clean energy innovation.

Single-cell transcriptomic and proteomic data from synovial tissue from individuals with rheumatoid arthritis classify patients into groups based on abundance of cell states that can provide insights into pathology and predict individual treatment responses.

Magnetic vortices in thin ferromagnetic films possess a core with out-of-plane magnetization whose polarity can be manipulated by magnetic fields or currents for technological applications. Here, the authors demonstrate local control of the core polarity in NiFe films via an imprinted maze domain pattern.

SCENT is a nonparametric method that models association between chromatin accessibility and gene expression in single-cell multimodal datasets, enabling construction of cell-type-specific enhancer–gene maps to aid mapping of candidate causal variants and genes for common diseases.

The mitochondrial phosphatase PPTC7 has previously been linked to the maintenance of mitochondrial content, but the mechanisms underlying this phenotype remain unclear. Here, the authors demonstrate that loss of Pptc7 results in metabolic defects and further suggest that PPTC7 is a regulator of receptor-mediated mitophagy.

Fibroblasts play critical roles in tissue homeostasis, but in pathologic states they can drive fibrosis, inflammation, and tissue destruction. Here, Faust et al. find that healthy human synovial fibroblasts under the influence of adjacent adipocytes have altered lipid metabolism driven by cortisol signaling. Both adipocytes and these characteristics are lost in inflammatory arthritis.

A large empirical assessment of sequence-resolved structural variants from 14,891 genomes across diverse global populations in the Genome Aggregation Database (gnomAD) provides a reference map for disease-association studies, population genetics, and diagnostic screening.

Anaplastic thyroid cancer (ATC) is a particularly aggressive cancer type with limited effective therapeutic options. Here, the authors identify the SUMO E3 ligase PIAS2 as a potential therapeutic target in ATC and mechanistically investigate its role in mitotic spindle and centrosome assembly.

Preliminary modelling of airborne microplastics suggests that they may be exerting a minor cooling influence on the present-day atmosphere, and continued production could have increasing effects on the climate system in future.

In this largest whole-exome sequencing study of epilepsies to date, the Epi25 Collaborative identified extremely rare variants that confer risk for diverse epilepsy subtypes, highlighting roles in synaptic transmission and neuronal excitability.

The epigenetic changes underlying the heterogeneity of RA disease presentation have been the subject of intense scrutiny. In this study, the authors use multiple single-cell sequencing datasets to define ‘chromatin superstates’ in patients with RA, which associate with distinct transcription factors and disease phenotypes.

NOTCH3 signalling is shown to be the underlying driver of the differentiation and expansion of a subset of synovial fibroblasts implicated in the pathogenesis of rheumatoid arthritis.

The dynamics of SARS-CoV-2 transmission in the Middle East have been relatively under-studied. Here, the authors integrate genomic and travel data and show that introductions to the region were initially driven by intercontinental air travel, after which regional land travel became a more important driver.

Whole-genome sequencing is used to analyse the landscape of somatic mutation in intestinal crypts from 16 mammalian species, revealing that rates of somatic mutation inversely scale with the lifespan of the animal across species.

A rare variant burden analytical framework for Mendelian diseases was developed and applied to data from the 100,000 Genomes Project, identifying 69 probable new disease–gene associations.

Idiopathic pulmonary fibrosis has been associated with aberrant expansion of KRT5-expressing basal cells. Here the authors show how changes in the ECM glycoprotein SPARC restrict the movement of KRT5+ cells, affecting their retention within fibrotic tissue.

This Consensus Statement clarifies the existing subset-based nomenclature for T cells. Furthermore, it proposes an alternative modular nomenclature that is designed to be brief and flexible and to avoid ambiguity and unwanted implications. The authors also provide guidance on how T cell nomenclature should be described in research papers.

Transcriptomic analysis of BCR-ABL1 lymphoblastic leukemia identifies three subgroups, each associated with a maturation arrest at a specific stage of B-cell progenitor differentiation and distinct genetic and clinical features.

Identifying and quantifying dissimilarities among graphs is a problem of practical importance, but current approaches are either limited or computationally demanding. Here, the authors propose an efficiently computable measure for network comparison that can identify structural topological differences.

Under continued global warming, lakes will increasingly be covered by white ice, in particular towards the end of the ice cover season when fatal winter drownings occur most often and light limits the growth and reproduction of primary producers.

Genetic and testing data from England show that the SARS-CoV-2 variant of concern B.1.1.7 has a transmission advantage over other lineages.

Post-international travel quarantine has been widely implemented to mitigate SARS-CoV-2 transmission, but the impacts of such policies are unclear. Here, the authors used linked genomic and contact tracing data to assess the impacts of a 14-day quarantine on return to England in summer 2020.

In this study, Aggarwal and colleagues perform prospective sequencing of SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge. They identify important factors that contributed to within university transmission and onward spread into the wider community.

A genomic constraint map for the human genome constructed using data from 76,156 human genomes from the Genome Aggregation Database shows that non-coding constrained regions are enriched for regulatory elements and variants associated with complex diseases and traits.

Structures that can enhance the capabilities of quantum cascade lasers are highly sought after to improve their practicality for a range of applications. Here the authors demonstrate such a structure in a saturable absorber that takes advantage of intersubband polaritons in the terahertz range and study coherent nonlinear dynamics in the system.

A survey of sharks and rays on coral reefs within 66 marine protected areas across 36 countries showcases that the conservation benefits of full MPA protection to sharks almost double when accompanied by effective fisheries management.

A proteomic risk score for cardiorespiratory fitness, comprising as few as 21 proteins, is dynamic with exercise training and helps predict the risk of mortality and a range of cardiovascular, metabolic and neurological conditions.

Insufficient AHR activation has been suggested in SLE, and augmenting AHR activation therapeutically may prevent CXCL13⁺ T_PH/T_FH differentiation and the subsequent recruitment of B cells and formation of lymphoid aggregates in inflamed tissues.

A novel variant annotation metric that quantifies the level of expression of genetic variants across tissues is validated in the Genome Aggregation Database (gnomAD) and is shown to improve rare variant interpretation.

Fishing has had a profound impact on global reef shark populations, and the absence or presence of sharks is strongly correlated with national socio-economic conditions and reef governance.

A catalogue of predicted loss-of-function variants in 125,748 whole-exome and 15,708 whole-genome sequencing datasets from the Genome Aggregation Database (gnomAD) reveals the spectrum of mutational constraints that affect these human protein-coding genes.

Automated pathotyping of synovial tissue in arthritis is a major unmet need. Here, the authors develop and demonstrate the efficacy of an automated tissue and cellular pathotyping tool for inflammatory arthritis.

A strategy for inferring phase for rare variant pairs is applied to exome sequencing data for 125,748 individuals from the Genome Aggregation Database (gnomAD). This resource will aid interpretation of rare co-occurring variants in the context of recessive disease.

The MSL complex acts on chromatin to and is required for X-chromosome dosage compensation. Chromatin-interacting protein MS (ChIP-MS) is now used to identify proteins and histone modifications interacting with the MSL complex, leading to the identification of CG4747. Functional analysis indicates that this protein is involved in targeting MSL to H3K36me3-containing chromatin.

Optogenetics, the optical stimulation of neurons, suffers from many technical challenges that limit the number of neurons that can be excited as well as their relative positions. Here, Pégard et al. develop a method to simultaneously stimulate an arbitrary number of neurons in 3D space with single neuron resolution.