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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.

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.

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.

An expanded GWAS of birth weight and subsequent analysis using structural equation modeling and Mendelian randomization decomposes maternal and fetal genetic contributions and causal links between birth weight, blood pressure and glycemic traits.

Exome sequencing and copy number analysis are used to define genomic aberrations in early sporadic pancreatic ductal adenocarcinoma; among the findings are mutations in genes involved in chromatin modification and DNA damage repair, and frequent and diverse somatic aberrations in genes known as embryonic regulators of axon guidance.

The GREGoR consortium provides foundational resources and substrates for the future of rare disease genomics.

Next-generation metagenomic testing increases the accuracy and sensitivity of the etiology of central nervous system infections in hospitalized patients.

Reference assemblies of great ape sex chromosomes show that Y chromosomes are more variable in size and sequence than X chromosomes and provide a resource for studies on human evolution and conservation genetics of non-human apes.

G-quadruplex are higher-order nucleotide structures within G-rich sequences with regulatory roles. Here, the authors provide the structure of a viral genomic RNA G-quadruplex using X-ray crystallography. They report unusual features of the West Nile virus NS5B quadruplex which expands our knowledge of quadruplex complexity and will aid in designing molecules to target them.

Modeling shows that antiretroviral treatment as pre-exposure prophylaxis (PrEP) can be highly effective in cisgender women at preventing HIV-1 acquisition, but underscores the need to understand the barriers that limit PrEP adherence in women.

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

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.

The potential for enhanced sediment delivery to the Ganges-Brahmaputra delta exists, but it alone is insufficient to sustain the system. The delta may be resilient to climate change, but only in the absence of dam construction and water diversions.

The genetics and clinical consequences of resting heart rate (RHR) remain incompletely understood. Here, the authors discover new genetic variants associated with RHR and find that higher genetically predicted RHR decreases risk of atrial fibrillation and ischemic stroke.

GWAS have identified more than 500 genetic loci associated with blood lipid levels. Here, the authors report a genome-wide analysis of interactions between genetic markers and physical activity, and find that physical activity modifies the effects of four genetic loci on HDL or LDL cholesterol.

Observations from the Lucy spacecraft of the small main-belt asteroid (152830) Dinkinesh reveals unexpected complexity, with a longitudinal trough and equatorial ridge, as well as the discovery of the first contact binary satellite.

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.

The sustainability of the majority of multispecies reef fisheries around the globe remains unassessed. This study provides context-specific sustainable reference points for coral reef fish using environmental conditions. Using these reference points, they show that most reef fish stocks have failed at least one fisheries sustainability benchmark.

Analysis of mitochondrial genomes (mtDNA) by using whole-genome sequencing data from 2,658 cancer samples across 38 cancer types identifies hypermutated mtDNA cases, frequent somatic nuclear transfer of mtDNA and high variability of mtDNA copy number in many cancers.

Climate affects dynamics of infectious diseases, but the impact on respiratory syncytial virus (RSV) epidemiology isn’t well understood. Here, Baker et al. model the influence of temperature, humidity and rainfall on RSV epidemiology in the USA and Mexico and predict impact of climate change on RSV dynamics.

Long-term expression of AAV transgenes in macaque liver is traced to integrated vectors.

The influence of X chromosome genetic variation on blood lipids and coronary heart disease (CHD) is not well understood. Here, the authors analyse X chromosome sequencing data across 65,322 multi-ancestry individuals, identifying associations of the Xq23 locus with lipid changes and reduced risk of CHD and diabetes mellitus.

Here we describe an open collaborative effort termed the ‘Ruminant T2T Consortium’. It aims to generate complete diploid assemblies for many species of ruminants to examine chromosomal evolution in the context of natural selection and domestication.

A genetic study identifies hundreds of loci associated with risk tolerance and risky behaviors, finds evidence of substantial shared genetic influences across these phenotypes, and implicates genes involved in neurotransmission.

Fine-mapping of causal variants and integration of epigenetic and chromatin conformation data identify likely target genes for 150 breast cancer risk regions.

Knowledge about the full reaction signature, such as the complete profile of products and side-products is important in accelerating discovery chemistry. Here, the authors report a methodology using high-throughput experimentation and multivariate data analysis to examine Palladium- catalyzed cross-coulpling reactions.

Vaccination is effective in protecting from COVID-19. Here the authors report immune responses and breakthrough infections in twice-vaccinated patients receiving anti-TNF treatments for inflammatory bowel disease, and find dampened vaccine responses that implicate the need of adapted vaccination schedules for these patients.

Gas exchange for photosynthesis occurs via stomata on the leaf surface and the airspace in the underlying mesophyll tissue. Here, the authors show that stomatal function modulates mesophyll airspace formation and that their coordinated development influences water use efficiency in crops

Analysis of whole-genome sequencing data across 2,658 tumors spanning 38 cancer types shows that chromothripsis is pervasive, with a frequency of more than 50% in several cancer types, contributing to oncogene amplification, gene inactivation and cancer genome evolution.

Variability in human longevity is genetically influenced. Using genetic data of parental lifespan, the authors identify associations at HLA-DQA/DRB1 and LPA and find that genetic variants that increase educational attainment have a positive effect on lifespan whereas increasing BMI negatively affects lifespan.

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.

Comprehensive integration of gene expression with epigenetic features is needed to understand the transition of kidney cells from health to injury. Here, the authors integrate dual single nucleus RNA expression and chromatin accessibility, DNA methylation, and histone modifications to decipher the chromatin landscape of the kidney in reference and adaptive injury cell states, identifying a transcription factor network of ELF3, KLF6, and KLF10 which regulates adaptive repair and maladaptive failed repair.

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.

Efficient, large-scale genomic analysis is facilitated on the cloud by a computational tool with error-diagnosing and self-healing capabilities.

Paul Pharoah and colleagues report the results of a large genome-wide association study of ovarian cancer. They identify new susceptibility loci for different epithelial ovarian cancer histotypes and use integrated analyses of genes and regulatory features at each locus to predict candidate susceptibility genes, including OBFC1.

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.

The wetting behaviour of drops attached to fibres is exploited in many applications including fog harvesting. The presence of a background air flow on fibre-attached drops on parallel fibres is now shown to lead to alignment, repulsion and coalescence processes.

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.

Drugs targeting cardiovascular disease (CVD) can have negative consequences for liver function. Here, the authors combine genome wide analyses on 69,479 individuals to identify loss-of-function variants with beneficial effects on CVD-related traits without negative impacts on liver function.

Fine-scale estimates of the prevalence of HIV in adults across sub-Saharan Africa reveal substantial within-country variation and local differences in both the direction and rate of change in the prevalence of HIV between 2000 and 2017.

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.

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.

Extrusion-based bioprinting has been shown to rapidly and reproducibly generate kidney organoids from a cell-only paste, with the number and maturation of functional units within the kidney tissue capable of being further improved by bioprinting tissue sheets.

To mature, dendritic cells collect and synthesize cholesterol to construct lipid nanodomains on their membranes. Obstructing this process impairs their ability to prime T cells.

HIV-1 vaccine design aims to induce broadly neutralizing antibodies such as IOMA, the only described antibody in its class. Here, the authors present the isolation, characterisation and structure of three additional antibodies within the IOMA class

A whole-genome sequencing analysis of 100 pancreatic ductal adenocarcinomas has discovered known and newly identified genetic drivers of pancreatic cancer; these genetic alterations can be classified into four subtypes, which raises the possibility of improved targeting of clinical treatments.

Whole-genome sequencing, transcriptome sequencing and single-cell analysis of primary and metastatic pancreatic adenocarcinoma identify molecular subtypes and intratumor heterogeneity.

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.

The seeding of native species is critical to the success of dryland restoration efforts. Here the authors evaluate success of seeding establishment at 174 sites on six continents, finding that some sites had nearly 100% of species successfully recruit, while 17% of sites had zero seedling success.

A family of calcium-dependent protein kinases (CDPK) is present in apicomplexan parasites but not in animals, indicating their potential as targets for anti-parasitic drugs. Structural and functional studies on Toxoplasma gondii CDPK1 now reveal that this kinase is sensitive to a class of drugs called bumped kinase inhibitors, which can inhibit the parasite's growth and host cell invasion.