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Which combination of current genome sequencing and assembly approaches results in high-quality, complete diploid genome assemblies is determined.

Unimolecular integration of NMDA receptor antagonism with GLP-1 receptor agonism effectively reverses obesity, hyperglycaemia and dyslipidaemia in rodent models of metabolic disease.

Immune lymphocyte estimation from nucleotide sequencing (ImmuneLENS) infers B cell and T cell fractions from whole-genome sequencing data. Applied to the 100,000 Genomes Project datasets, circulating T cell fraction provides sex-dependent and prognostic insights in patients.

Genomic studies often lack representation from diverse populations, limiting equitable insights. Here, the authors show that the BIG Initiative captures extensive genetic diversity and reveals ancestry-linked health disparities in a community-based Mid-South cohort.

This report by the Consortium for Refractive Error and Myopia uses gene-environment-wide interaction study (GEWIS) to identify genetic loci that affect environmental influence in myopia development, and identifies ethnic specific genetic loci that attribute to eye refractive errors.

Genome-wide association meta-analysis of AAA identifies 121 independent risk loci and highlights potential therapeutic targets such as proprotein convertase, subtilisin/kexin-type 9 (PCSK9).

Radiation-induced gliomas (RIGs) have been reported in patients after treatment with cranial irradiation for various primary malignancies but their origin are still unclear. Here, the authors define the genomic, epigenetic and transcriptional landscape of 32 RIGs cases.

Tree functional strategies regulate responses to water stress, but how these strategies scale up to the forest community level is not well known. This study shows coherent spatial variation in community-level trait associations across temperate forests that is linked to temperature.

Blood pressure (BP) is a major risk factor for cardiovascular disease and more than 200 genetic loci associated with BP are known. Here, the authors perform discovery GWAS for BP in East Asians and meta-analysis in East Asians and Europeans and report ancestry-specific BP SNPs and selection signals.

An analysis of 52 million births in 26 countries shows small reductions in preterm birth during the first to third months of lockdown. Further research is needed to examine causal pathways.

Post-fast refeeding increases intestinal stem cell function and tumour formation by augmenting protein synthesis via polyamine metabolism.

Whole-exome sequencing identifies ten risk genes for schizophrenia implicated by rare protein-coding variants, a subset of which overlap with risk genes in other neurodevelopmental disorders.

Adenylyl cyclases (ACs) generate the second messenger cAMP and play an important role in cellular signaling. Here, the authors use cryo-EM to trace the conformational changes resulting from binding to partial and full activators to one of these enzymes, AC9.

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.

The role of olfactory pathways in the development of neurodegeneration in Alzheimer’s disease is not well understood. Here, the authors show odor identification deficits are predictive of tau accumulation and progression in olfactory pathways, and that tau spreads from medial temporal lobe structures towards the olfactory system.

In this Consensus Statement, an international panel of experts present an overview of the latest developments in the field of cholangiocarcinoma. A set of consensus recommendations and research priorities is provided.

Benchmarking of tumor subclonal reconstruction algorithms finds that interalgorithm variability overwhelms intertumor variability and identifies key quality metrics.

Sarcomas are morphologically heterogeneous tumours rendering their classification challenging. Here the authors developed a classifier using DNA methylation data from several soft tissue and bone sarcoma subtypes, which has the potential to improve classification for research and clinical purposes.

Naïve pluripotency is characterized by distinctly open chromatin and repressed endogenous retroviruses. Here the authors show that MPP8 and its association with the core HUSH complex is essential for naïve pluripotent cells; also that repression of LINE1 elements by MPP8 does not require chromatin binding, nor H3K9me3.

Miscarriage affects around 15% of clinically confirmed pregnancies. Here the authors carry out a large genome-wide association study for sporadic and multiple consecutive miscarriage and suggest links with placental biology.

The first operation of the European X-ray free-electron laser facility accelerator based on superconducting technology is reported. The maximum electron energy is 17.5 GeV. A laser average power of 6 W is achieved at a photon energy of 9.3 keV.

A meta-analysis of genome-wide association study data from 77,418 individuals of East Asian ancestry with type 2 diabetes identifies novel variants associated with increased risk of type 2 diabetes.

A pooled analysis of longitudinal studies in low- and middle-income countries identifies the typical age of onset of linear growth faltering and investigates recurrent faltering in early life.

Advances in electron cryo-microscopy hardware allow proteins to be studied at atomic resolution.

In lung cancer, relatively few germline mutations are known to impact risk. Here the authors looked at rare variants in 39,146 individuals and find novel germline mutations associated with risk, as well as implicating ATM and a new candidate gene for lung cancer risk.

A detailed understanding of the catalytic target DNA cleavage mechanism by CRISPR–Cas9 has been lacking. Now the key modulating role of Mg²⁺ in the conformational activation of Cas9 and the influence of active site residues on the protonation state of catalytic H840 are demonstrated, ultimately unravelling the catalytic mechanism.

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.

Identifying therapeutic targets in rare cancers is challenging due to the lack of relevant pre-clinical models. Here, the authors generate a cancer cell line from a paediatric patient with a rare undifferentiated sarcoma and through functional genomics and chemical screens identified CDK4 and XPO1 as potential therapeutic targets in this cancer.

The diverse makeup and assembly of subunits augment the structure, physiology and pharmacology of GABA_A receptors.

Efficient qubit readout is essential for quantum information technology, which requires sufficient recognition of signal from noise. Here, Krantz et al. propose a simplified technique using a Josephson parametric oscillator, demonstrating single-shot readout performance of a superconducting qubit.

Ancient proteins in human dental calculus from sites across Mongolia spanning 5,000 years suggest dairy consumption on the eastern Eurasian steppe by circa 3000 bc, and the later emergence of horse milking at circa 1200 bc, concurrent with the first evidence for horse riding.

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.

Genome-wide analyses identify 27 loci associated with attention-deficit hyperactivity disorder and provide insights into its genetic architecture in relation to other psychiatric disorders and cognitive traits.

High-resolution subnational mapping of child growth failure indicators for 105 low- and middle-income countries between 2000 and 2017 shows that, despite considerable progress, substantial geographical inequalities still exist in some countries.

Sequential generation of layer-specific cortical neurons requires radial glial cells (RGCs) to balance self-renewal and commitment. Here the authors show that RGCs and lineage committed progenitors are defined by distinct cell cycle phases and CYCLIN-B1/2 cooperates with CDK1 to activate Notch and maintain RGCs.

Most DNA-encoded library (DEL) syntheses are limited by the presence of sensitive DNA-based constructs. Here, the authors develop DOSEDO, a diverse 3.7 million compound DEL, generated through diversity-oriented synthesis that provides enhanced scaffold and exit vector diversity and gives validated binding hits for multiple protein targets.

Comparisons within the human pangenome establish that homologous regions on short arms of heterologous human acrocentric chromosomes actively recombine, leading to the high rate of Robertsonian translocation breakpoints in these regions.

Measuring photoionization time delays is an interesting and challenging topic. Here the authors demonstrate a method to measure the photoionization time delays using inner-shell ionization of CO molecule.

Federated ML (FL) provides an alternative to train accurate and generalizable ML models, by only sharing numerical model updates. Here, the authors present the largest FL study to-date to generate an automatic tumor boundary detector for glioblastoma.

Functionalized InAs quantum dots emitting in the short-wavelength infrared spectral region enable functional biomedical imaging at unprecedentedly high spatial resolution, deep penetration and fast acquisition speeds.

Birch pitch is thought to have been used in prehistoric times as hafting material or antiseptic and tooth imprints suggest that it was chewed. Here, the authors report a 5,700 year-old piece of chewed birch pitch from Denmark from which they successfully recovered a complete ancient human genome and oral microbiome DNA.

Neurotransmitter:sodium symporters (NSS) serve as targets for drugs including antidepressants and psychostimulants. Here authors report the X-ray structure of the prokaryotic NSS member, LeuT, in a Na⁺/substrate-bound, inward-facing occluded conformation which is a key intermediate in the LeuT transport cycle.

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.

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 laser-plasma electron beam generated using active energy compression demonstrates reduction in energy spread and jitter by an order of magnitude to below the permille level, comparable with modern radio-frequency accelerators.

Common polygenic variation at chromosome 16p and rare recurrent deletions of 16p11.2 influencing autism risk are associated with reduced expression of genes throughout the 16p region, suggesting functional convergence of rare and common variant effects.