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Past genome-wide associate studies have identified hundreds of genetic loci that influence body size and shape when examined one trait at a time. Here, Jeff and colleagues develop an aggregate score of various body traits, and use meta-analysis to find new loci linked to body shape.

This study uses a novel vascular model with human induced pluripotent stem cell-derived endothelial cells, pericytes, and smooth muscle cells to explore the vascular complications associated with SARS-CoV-2. It reveals that smooth muscle cells as the primary sites of infection and inflammation.

The authors defined a roadmap for investigating the genetic covariance between structural or functional brain phenotypes and risk for psychiatric disorders. Their proof-of-concept study using the largest available common variant data sets for schizophrenia and volumes of several (mainly subcortical) brain structures did not find evidence of genetic overlap.

Strontium isotope analysis can be applied to animal and plant tissues to help determine their provenance. Here, the authors generate a strontium isoscape of sub-Saharan Africa using data from 2266 environmental samples and demonstrate its efficacy by tracing the African roots of individuals from historic slavery contexts.

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.

Genome-wide ancient DNA data from individuals from the Middle Bronze Age to Iron Age documents large-scale movement of people from the European continent between 1300 and 800 bc that was probably responsible for spreading early Celtic languages to Britain.

Small-scale farmers in Southeast Asia are increasingly turning to monocultures of oil palm and rubber to maximize income. Clough and colleagues demonstrate that this land-use change in Indonesia comes at a cost to a wide array of ecosystem functions and biodiversity.

Primary open-angle glaucoma (POAG) is highly heritable, yet not well understood from a genetic perspective. Here, the authors perform a meta-analysis of genome-wide association studies in 34,179 POAG cases, identifying 44 previously unreported risk loci and mapping effects across multiple ethnicities.

Surveys from 2,584 sites across the Indo-Pacific identify key climate, socioeconomic and environmental drivers associated with hard coral assemblages. This informs a strategic approach to protect, recover or transform coral reef management.

In a GWAS study of 32,438 adults, the authors discovered five novel loci for intracranial volume and confirmed two known signals. Variants for intracranial volume were also related to childhood and adult cognitive function and to Parkinson's disease, and enriched near genes involved in growth pathways, including PI3K-AKT signaling.

This meta-analysis of genome-wide association studies identifies four genetic loci associated with circulating leptin levels independent of adiposity. Examination in mouse adipose tissue explants provides functional support for the leptin-associated loci.

The root of the eukaryote Tree of Life is estimated from a new, larger dataset of mitochondrial proteins including all known eukaryotic supergroups, showing it lies between two multi-supergroup assemblages.

The beetle Tribolium castaneum is a commonly used laboratory model, combining the ease of systematic RNAi experiments like those in Caenorhabditis elegans, with biology that is more representative of most insects than Drosophila melanogaster. A large consortium has sequenced and analysed the genome of the red flour beetle, creating a resource for biologists everywhere.

A case–control study investigating the causes of recent cases of acute hepatitis of unknown aetiology in 32 children identifies an association between adeno-associated virus infection and host genetics in disease susceptibility.

The causative agent of sea star wasting disease has been elusive. This study used genetic datasets and experimental exposures to demonstrate that a strain of the bacterium Vibrio pectenicida caused disease and mortality in sea stars.

Three electron microscopy datasets are combined to provide a complete connectomic description of the neural circuitry that makes up the neck connective in Drosophila, including the descending neurons, ascending neurons and sensory ascending neurons.

Competition between agriculture and land conservation may hinder climate and biodiversity targets. Here, the authors use global models integrating multiple spatial scales to assess how ambitious land conservation action and associated land-use dynamics could drive changes in landscape heterogeneity, pollination supply and soil loss.

The prognosis of castration-resistant prostate cancers remains dismal, but accurate preclinical models can lead to effective therapies. Here the Melbourne Urological Research Alliance establish prostate cancer patient-derived xenografts, use the tumors for organoids and single-cell RNA-seq, and show the efficacy of PARP inhibitor combination treatments.

The SUMO-specific protease SENP1 is activated by binding of its substrate, SUMO1, to a site remote from the catalytic cleft. Chen et al. characterise the dynamic changes in SENP1 conformation associated with substrate binding, and reveal how they influence the catalytic activity of the enzyme.

Low read depth sequencing of whole genomes and high read depth exomes of nearly 10,000 extensively phenotyped individuals are combined to help characterize novel sequence variants, generate a highly accurate imputation reference panel and identify novel alleles associated with lipid-related traits; in addition to describing population structure and providing functional annotation of rare and low-frequency variants the authors use the data to estimate the benefits of sequencing for association studies.

Population-based genome sequencing provides an increasingly rich resource for the identification of low-frequency, large effect variants associated with clinically important phenotypes. Timpson et al. use UK10K data to identify a variant of the APOC3gene strongly associated with plasma triglyceride levels.

The CNV analysis group of the Psychiatric Genomic Consortium analyzes a large schizophrenia cohort to examine genomic copy number variants (CNVs) and disease risk. They find an enrichment of CNV burden in cases versus controls and identify 8 genome-wide significant loci as well as novel suggestive loci conferring either risk or protection to schizophrenia.

Post-translational site-selective formation of boronoalanine in proteins enables applications of boron for binding partner capture, footprinting of interactions with reactive oxygen species, proteolytic control and mapping of transient structures.

X-ray fee-electron lasers (XFELs) enable time-resolved crystallography experiments and the structure determination of proteins with little or no radiation damage. However currently it is unknown whether the designated 4.5 MHz maximum pulse rate for the European XFEL could lead to sample damage caused by shock waves from preceding pulses. Here, the authors address this question by performing a X-ray pump X-ray probe experiment on haemoglobin microcrystals at the Stanford XFEL facility that mimics the 4.5 MHz data collection mode and observe structural changes and a drop in diffraction data quality of the crystals.

A genome-wide association meta-analysis study here shows novel genetic loci to be associated to body fat percentage, and describes cross-phenotype association that further demonstrate a close relationship between adiposity and cardiovascular disease risk.

Combination of epidemiology, preclinical models and ultradeep DNA profiling of clinical cohorts unpicks the inflammatory mechanism by which air pollution promotes lung cancer

The activity of PD-1 blockade in patients with sarcoma has been modest so far. Here, the authors report the results of a pilot clinical trial to assess the efficacy and safety of bempegaldesleukin, a CD122-preferential interleukin-2 (IL-2) pathway agonist, in combination with the PD1 blockade (nivolumab) in patients with locally advanced or metastatic high-grade sarcoma.

Sexual dimorphism in genetic vulnerability to schizophrenia, systemic lupus erythematosus and Sjögren’s syndrome is linked to differential protein abundance from alleles of complement component 4.

Results of the TRACERx study shed new light into the association between body composition and body weight with survival in individuals with non-small cell lung cancer, and delineate potential biological processes and mediators contributing to the development of cancer-associated cachexia.

A stiff hydrogel gel is presented that encapsulates and stabilizes proteins without additives or excipients and uses mechanical strain to release them, offering low-cost and versatile delivery of therapies.

Patient-derived xenografts are important tools for cancer drug development. Here, the authors develop models from 22 non-small cell lung cancer patients. They show genomic differences between models created from different spatial regions of tumours and a bottleneck on model establishment.

Mixed responses to targeted therapy within a patient are a clinical challenge. Here the authors show that TP53 loss-of-function cooperates with whole genome doubling which increases chromosomal instability. This leads to greater cellular diversity and multiple routes of resistance, which in turn promotes mixed responses to treatment.

Panzeri et al. use a Trim28^+/D9 mouse model with intrinsic developmental heterogeneity to show that ‘heavy’ and ‘light’ developmental morphs exhibit different timing, type and severity of cancer, linked to a relevant DNA hypomethylation signature.

Genome-wide analysis identifies 30 loci associated with bipolar disorder, allowing for comparisons of shared genes and pathways with other psychiatric disorders, including schizophrenia and depression.

Size and shape of the brain are, among others, influenced by the dimensions of the skull. Here, the authors report genome-wide association studies for head circumference and intracranial volume in children and adults and the identification of nine common or low-frequency variants associated with these traits.

Sequencing the genomes of two enteropneusts reveals complex genomic organization and developmental innovation in the ancestor of deuterostomes, a group of animals including echinoderms (starfish and their relatives) and chordates (which includes humans).

Imputation uses genotype information from SNP arrays to infer the genotypes of missing markers. Here, the authors show that an imputation reference panel derived from whole-genome sequencing of 3,781 samples from the UK10K project improves the imputation accuracy and coverage of low frequency variants compared to existing methods.

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.

Archival images of the progenitor system of supernova SN 2011fe are so sensitive that the presence of luminous red giants or most helium stars is directly ruled out.

Previous work has identified several genes where mutations lead to breast cancer, but other genetic and environmental factors must still be accounted for. A large study of genetic association with breast cancer points to four novel genes and many more genetic markers that should be pursued for their link to cancer susceptibility.

Analyses of the TRACERx study unveil the relationship between tissue morphology, the underlying evolutionary genomic landscape, and clinical and anatomical relapse risk of lung adenocarcinomas.

An integrated transcriptome, genome, methylome and proteome analysis of over 200 lung adenocarcinomas reveals high rates of somatic mutations, 18 statistically significantly mutated genes including RIT1 and MGA, splicing changes, and alterations in MAPK and PI(3)K pathway activity.

Archaeogenetic study of ancient DNA from medieval northwestern Europeans reveals substantial increase of continental northern European ancestry in Britain, suggesting mass migration across the North Sea during the Early Middle Ages.

Unprecedented floods and droughts bring new challenges for risk reduction, as is clear from this analysis of the drivers of changing impacts in many cases worldwide, with implications for efficient governance and investment in integrated management.