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Concerns have been raised regarding potential increase in the virulence of the Ebola virus during the current West African outbreak. Here the authors show that the ability to inhibit interferon response, one of the aspects of Ebola virus virulence, does not differ between the prototype Mayinga and isolates from the current outbreak.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

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.

Analysis of whole-genome sequences of 25,465 individuals of European ancestry shows that rare variants contribute substantially to the heritability of height and body mass index.

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.

A comparison of two complete sets of human centromeres reveals that the centromeres show at least a 4.1-fold increase in single-nucleotide variation compared with their unique flanks, and up to 3-fold variation in size, resulting from an accelerated mutation rate.

Necroptosis is a regulated form of inflammatory cell death driven by activated MLKL. Here, the authors identify a mutation in the brace region that confers constitutive activation, leading to lethal inflammation in homozygous mutant mice and providing insight into human mutations in this region.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

A study proposes four ways in which foods sourced in aquatic environments can contribute to healthier, more environmentally sustainable and equitable food systems, and examines the relevance of these ambitions to nations.

Inbreeding depression has been observed in many different species, but in humans a systematic analysis has been difficult so far. Here, analysing more than 1.3 million individuals, the authors show that a genomic inbreeding coefficient (FROH) is associated with disadvantageous outcomes in 32 out of 100 traits tested.

Policies that centre principles of justice and human rights, specify inclusive decision-making processes and identify and challenge underlying drivers of injustice are linked to more just food system outcomes.

Safely opening university campuses has been a major challenge during the COVID-19 pandemic. Here, the authors describe a program of public health measures employed at a university in the United States which, combined with other non-pharmaceutical interventions, allowed the university to stay open in fall 2020 with limited evidence of transmission.

Using data from a single time point, passenger-approximated clonal expansion rate (PACER) estimates the fitness of common driver mutations that lead to clonal haematopoiesis and identifies TCL1A activation as a mediator of clonal expansion.

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.

The goals, resources and design of the NHLBI Trans-Omics for Precision Medicine (TOPMed) programme are described, and analyses of rare variants detected in the first 53,831 samples provide insights into mutational processes and recent human evolutionary history.

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 study shows that clonal haematopoiesis of indeterminate potential is associated with an increased risk of chronic liver disease specifically through the promotion of liver inflammation and injury.

Post-acute sequelae of SARS-CoV-2 (PASC) is still not well understood. Here the authors provide patient reported outcomes from 590 hospitalized COVID-19 patients and show association of PASC with higher respiratory SARS-CoV-2 load and circulating antibody titers, and in some an elevation in circulating fibroblast growth factor 21.

Hepatic bone morphogenetic protein 8b expression is shown to be induced in NASH to drive wound healing responses and NASH progression by promoting inflammatory pathways in hepatic stellate cells and, more broadly, in the liver parenchyma.

Most studies of the genetics of the metabolome have been done in individuals of European descent. Here, the authors integrate genomics and metabolomics in Black individuals, highlighting the value of whole genome sequencing in diverse populations and linking circulating metabolites to human disease.

Although the common genetic variants contributing to blood lipid levels have been studied, the contribution of rare variants is less understood. Here, the authors perform a rare coding and noncoding variant association study of blood lipid levels using whole genome sequencing data.

STAARpipeline is a comprehensive framework for flexible and scalable rare-variant association analysis using whole-genome sequencing data and annotation information.

Polygenic risk scores predict the likelihood that an individual will develop a certain cancer, however these are often specific for a given population. Here, the authors show that a risk score developed to assess the risk of breast cancer in European women can also predict risk in Asian populations.

Data on the nutrient content of almost 3,000 aquatic animal-source foods is combined with a food-systems model to show that an increase in aquatic-food production could reduce the inadequate intake of most nutrients.

The tumor suppressor PTEN antagonizes the PI3K signalling pathway and is frequently inactivated in haematological malignancies. Here, the authors unravel the main contribution of the PI3K isoform p110ß to leukemic transformation driven by PTEN-loss.

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.

Analysis of 97,691 high-coverage human blood DNA-derived whole-genome sequences enabled simultaneous identification of germline and somatic mutations that predispose individuals to clonal expansion of haematopoietic stem cells, indicating that both inherited and acquired mutations are linked to age-related cancers and coronary heart disease.

A study of SARS-CoV-2 variants examining their transmission, infectivity, and potential resistance to therapies provides insights into the biology of the Delta variant and its role in the global pandemic.

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.

Forkhead box transcription factor, FOXQ1 is reported to promote epithelial-mesenchymal transition (EMT) and cancer metastasis. Here the authors show that FOXQ1 recruits the KMT2/MLL histone methyltransferase complex as a transcriptional coactivator to activate EMT programme in breast cancer.

Children with type 1 diabetes (T1D) are at risk for reduced cognitive ability and atypical brain development. This study shows that brain and cognitive measures can be improved in adolescents with T1D using a semi-automated insulin delivery system.

The nutritional, economic and livelihood contributions provided by aquatic food systems are threatened by climate change. Building climate resilience requires systemic interventions that reduce social vulnerabilities.

Disease signatures in high-dimensional biomedical data are detected with a visualization algorithm.

SARS-CoV-2 infection can lead to progressive pathology in patients with COVID-19, but information for this disease progression is sparse. Here the authors use multi-omics approach to profile the immune responses of patients, assessing immune repertoire and effects of tocilizumab treatments, to find a dyssynchrony between innate and adaptive immunity in progressive COVID-19.

Individuals over eighty years of age are less likely to mount a good immune response against SARS-CoV-2 (measured by neutralization titres) after the first dose of the BNT162b2 mRNA vaccine, but achieve good neutralization after the second dose.

Transcriptomic and proteomic profiling of blood samples from individuals with COVID-19 reveals immune cell and hematopoietic progenitor cell alterations that are differentially associated with disease severity.

Meaningful involvement of patients in clinical trial design could lead to improvements in participant recruitment and retention, the uptake of the tested intervention and the impact of the findings. Here, the authors discuss the involvement of patients at all stages of trial design.

MetaSTAAR enables functionally informed rare variant association analysis in biobank-scale cohorts using an efficient, sparse matrix approach for summary statistic storage.

In this work, an injectable, self-healing hydrogel with antibacterial and angiogenic abilities was prepared based on the coordination of multi-arm thiolated polyethylene glycol (SH-PEG) with antibacterial silver ions (Ag⁺). The injectable and self-healing properties derive from the dynamic nature of the Ag-S coordination bonds. After incorporation of an angiogenic drug desferrioxamine (DFO), we could obtain a multifunctional hydrogel with manageable, resistant to external stress, antibacterial and angiogenic properties. Such unique multifunctional hydrogel thus shows potential to accelerate the healing of some exposed wounds (e.g., diabetic skin wound) under disturbed physiological functions, high risk of bacterial infections, and external mechanical irritation.

A framework for capturing the key dimensions of small-scale actors in aquatic food supply chains is explored—with recommendations for supporting their viability and adaptability in sustainable food systems

A high-resolution reference panel based on whole-genome sequencing data enables accurate imputation of HLA alleles across diverse populations and fine-mapping of HLA association signals for HIV-1 host response.

STAAR is a powerful rare variant association test that incorporates variant functional categories and complementary functional annotations using a dynamic weighting scheme based on annotation principal components. STAAR accounts for population structure and relatedness and is scalable for analyzing large whole-genome sequencing studies.

An analysis of 16 health-related quantitative traits in approximately 350,000 individuals reveals statistically significant associations between genome-wide homozygosity and four complex traits (height, lung function, cognitive ability and educational attainment); in each case increased homozygosity associates with a decreased trait value, but no evidence was seen of an influence on blood pressure, cholesterol, or ten other cardio-metabolic traits.

Membranous nephropathy is a glomerular disease that is the most frequent cause of nephrotic syndrome in adults. This Primer reviews the epidemiology, pathophysiology, diagnosis and management of this disease and discusses how to improve long-term renal prognosis and quality of life.