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Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

Analysis of samples from the asteroid Ryugu provide evidence of late fluid flow in a carbonaceous asteroid, indicating that such bodies may have retained two to three times more water than previously thought.

Phylogenomic analysis of 7,923 angiosperm species using a standardized set of 353 nuclear genes produced an angiosperm tree of life dated with 200 fossil calibrations, providing key insights into evolutionary relationships and diversification.

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.

Analysing the distributions of >99% of the world’s seed plant flora, the authors find evidence supporting the evolutionary imbalance hypothesis, with species originating from large, biodiverse regions being more successful at naturalizing beyond their native ranges.

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.

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 genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

A study reports whole-genome sequences for 490,640 participants from the UK Biobank and combines these data with phenotypic data to provide new insights into the relationship between human variation and sequence variation.

The analysis of pairs of identical SARS-CoV-2 genome sequences enables characterization of transmission patterns between geographies and age groups.

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 advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

A comparison of copper and zinc isotopic measurements between the Ryugu samples and various carbonaceous chondrites excludes any genetic link between the two except for the CI (Ivuna-type) chondrites. Ryugu-like material might have accounted for ~5% of Earth’s mass.

How the immune response is involved in the response to multiple myeloma after treatment is not fully understood. Here the authors investigate how lenalidomide treatment in newly diagnosed MM patients affects the immune microenvironment in the blood and bone marrow and compare between responses to treatment.

Lineage tracing of human stem cells is achieved by measuring fluctuating DNA methylation.

AlphaStar uses a multi-agent reinforcement learning algorithm and has reached Grandmaster level, ranking among the top 0.2% of human players for the real-time strategy game StarCraft II.

Integration of mathematical modeling, ecological analyses of patient biopsies, and neoantigen heterogeneity suggests recruitment of immunosuppressive cells is key to initializing transformation from adenoma to carcinoma in human colorectal cancer.

The asteroid Ryugu experienced aqueous alteration under changing temperature and redox conditions, according to an isotopic analysis of secondary calcite and dolomite grains in samples from Ryugu obtained by the Hayabusa2 spacecraft.

COVID-19 can be associated with neurological complications. Here the authors show that markers of brain injury, but not immune markers, are elevated in the blood of patients with COVID-19 both early and months after SARS-CoV-2 infection, particularly in those with brain dysfunction or neurological diagnoses.

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.

Trypanosomes evade the immune response through antigenic variation of a surface coat containing variant surface glycoproteins (VSG). They also express invariant surface glycoproteins (ISGs), which are less well understood. Here, Macleod et al. show that ISG65 of T. brucei is a receptor for complement component 3. They provide the crystal structure of T. brucei ISG65 in complex with complement C3d and show evidence that ISG65 is involved in reducing trypanosome susceptibility to C3-mediated clearance in vivo.

Three key axes of variation of ecosystem functional changes and their underlying causes are identified from a dataset of surface gas exchange measurements across major terrestrial biomes and climate zones.

A study establishes a scalable approach to engineer and characterize a many-body-localized discrete time crystal phase on a superconducting quantum processor.

Chiea Chuen Khor, Tin Aung, Francesca Pasutto, Janey Wiggs and colleagues report a global genome-wide association study of exfoliation syndrome and a fine-mapping analysis of a previously identified disease-associated locus, LOXL1. They identify a rare protective variant in LOXL1 exclusive to the Japanese population and five new common variant susceptibility loci.

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.

Analysis of gene expression and open chromatin regions in up to 32 immune cell populations under resting and stimulated conditions identifies widespread chromatin remodeling and shared response elements between stimulated B and T cells.

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.

Mismatch repair-deficient colorectal cancer clones adapt their mutation landscape by toggling homopolymer sequences in MutS homolog 3 (MSH3) and MutS homolog 6 (MSH6). This increases the subclonal mutation rate and clonal diversity, favoring immune escape and tumor growth.

A dataset of coding variation, derived from exome sequencing of nearly one million individuals from a range of ancestries, provides insight into rare variants and could accelerate the discovery of disease-associated genes and advance precision medicine efforts.

The neurochemical basis of compulsive behaviour is not well understood. Here, the authors show that levels of glutamate and GABA in the supplementary motor area and anterior cingulate cortex relate to compulsive behaviour in healthy controls and individuals with OCD.

The Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA) aims to better understand population genetics of the African diaspora. Here, it uses deeply sequenced whole-genomes to describe the impact of admixture and potential disease burden of deleterious variants.

AlphaFold predicts protein structures with an accuracy competitive with experimental structures in the majority of cases using a novel deep learning architecture.

Although circulating tumour DNA (ctDNA) can predict immune checkpoint blockade (ICB) responses, its association with tumour biomarkers remains unknown. Here, the authors use ctDNA to inform exome and transcriptome profiling of >100 patients with 30 cancer types on a single clinical ICB trial and identify tumour microenvironment features associated with response.

Antibody diversification relies on the intentional mutagenesis of immunoglobulin genes for adaptive immune responses. Here, the authors identified a CTLH E3 ubiquitin ligase complex that co-opts FAM72A to recruit and degrade the UNG2 base excision repair factor to permit mutagenesis.

Stig Bojesen, Georgia Chenevix-Trench, Alison Dunning and colleagues report common variants at the TERT-CLPTM1L locus associated with mean telomere length measured in whole blood. They also identify associations at this locus to breast or ovarian cancer susceptibility and report functional studies in breast and ovarian cancer tissue and cell lines.

SARS-CoV-2 constantly evolves but the roles of resulting mutations are not always clear. In this study, the authors report that ORF8 knockout confers a fitness advantage to SARS-CoV-2 using genomic surveillance data, highlighting how different types of adaptations across the SARS-CoV-2 genome can drive variant fitness.

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.

Temporal multi-omic analysis of tissues from rats undergoing up to eight weeks of endurance exercise training reveals widespread shared, tissue-specific and sex-specific changes, including immune, metabolic, stress response and mitochondrial pathways.

The Ep400 chromatin remodeler determines genomic distribution of variant histones. In the current study, the authors show that loss of Ep400 in Schwann cells leads to aberrant expression of developmental regulators, and a peripheral neuropathy phenotype.

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.

Metastatic prostate cancer can be difficult to biopsy and characterise. Here, the authors use cell-free DNA methylation analysis to illustrate changes in hypermethylation in metastatic disease.

Analyses of the relationships between temperature, moisture and seven key plant functional traits across the tundra and over time show that community height increased with warming across all sites, whereas other traits lagged behind predicted rates of change.

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

Multiple drivers maintain unique species assemblages at multiple biogeographic scales. Here, the authors show that the freezing line is a key barrier generating evolutionary differences in temperate and tropical bird communities across a steep elevational gradient in the Himalaya.

Split inteins are powerful tools for designing synthetic split proteins. Here the authors use a mini-Mu transposon screen to map split sites, enabling the development of protein-based logic gates and fine control of protein activity.

A genome-wide association study of critically ill patients with COVID-19 identifies genetic signals that relate to important host antiviral defence mechanisms and mediators of inflammatory organ damage that may be targeted by repurposing drug treatments.