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Available wheat genomes are annotated by projecting Chinese Spring gene models across the new assemblies. Here, the authors generate de novo gene annotations for the 9 wheat genomes, identify core and dispensable transcriptome, and reveal conservation and divergence of gene expression balance across homoeologous subgenomes.

Mutual paracrine regulation of the cytokines GREM1 and SPP1 mediate mesenchymal and epithelial cell fate in pancreatic cancer.

Circuit and cell type prioritization for complex disorders is crucial to direct future efforts. Here the authors integrate GWAS, human single-cell RNA-seq and fMRI analysis suggesting multi-modality convergence on amygdalar and hippocampal circuits.

Genome-wide maps of DNA methylation have so far been restricted to plants, animals and fungi. Here, the authors report the first whole-genome methylome of a stramenopile, the diatom Phaeodactylum tricornatum, and provide insight into the evolution of DNA methylation in eukaryotes.

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 transcriptomic cell-type atlas of the whole adult mouse brain with ~5,300 clusters built from single-cell and spatial transcriptomic datasets with more than eight million cells reveals remarkable cell type diversity across the brain and unique cell type characteristics of different brain regions. 

A comprehensive cell atlas of the aged prefrontal cortex identifies two distinct cellular trajectories of ageing driven by specific glial and neuronal subpopulations, some of which are associated with clinicopathologic traits that define Alzheimer’s disease.

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 affected cellular populations during Alzheimer’s disease progression remain understudied. Here the authors use a cohort of 84 donors, quantitative neuropathology and multimodal datasets from the BRAIN Initiative. Their pseudoprogression analysis revealed two disease phases.

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.

A national prospective study of patients requiring hospitalization for COVID-19 demonstrates global cognitive deficits at 1 year, associated with elevated brain injury markers and reduced gray matter volume.

This study uses epi-retro-seq to link single-cell epigenomes and cell types to long-distance projections for neurons dissected from different regions projecting to different targets across the whole mouse brain.

Blood biomarkers in a middle-aged population suggest that SARS-CoV-2 infection is associated with greater brain β-amyloid plaque accumulation.

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.

Patients with classic Hodgkin lymphoma (cHL) respond well to PD-1 blockade, but the underlying cellular insights are still lacking. Here, the authors use single-cell transcriptome and spatial analyses to identify distinct circulating and tumor-infiltrating CD4⁺ T cell, B cell and IL1β⁺ monocyte/macrophage features associated with response to PD-1 blockade in cHL.

Bacteriophage diversity in cell-free DNA within human plasma can help to specify pathogenic Escherichia coli and Staphylococcus aureus during sepsis.

A neuron-specific activity-dependent DNA repair mechanism is identified, the impairment of which may lead to neurodevelopmental disorders, neurodegeneration and ageing.

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 cross-ancestry genome-wide association meta-analysis of amyotrophic lateral sclerosis (ALS) including 29,612 patients with ALS and 122,656 controls identifies 15 risk loci with distinct genetic architectures and neuron-specific biology.

Whole-genome sequencing analysis of individuals with primary immunodeficiency identifies new candidate disease-associated genes and shows how the interplay between genetic variants can explain the variable penetrance and complexity of the disease.

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.

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 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.

Systematic studies are needed to discover molecular determinants of blood brain barrier dysfunction in Alzheimer’s disease. This study identifies perturbed pericytic SMAD3-astrocytic VEGFA interactions as a potential driver of this dysfunction.

This Review provides insights for construction of molecular cell atlases and outlines key study design considerations. The authors emphasize the power of single-cell and single-nucleus genomics in revealing cellular transitions during nervous system development and disease.

Data on the value of dietary supplements in reducing the risk of developing prostate cancer have been conflicting; however, two large randomized trials have indicated that prostate cancer risk is not reduced by the long-term use of vitamin E, vitamin C or selenium supplements.

The emergence of large-scale genomics projects has led to genetic studies across cohorts. Here, the authors conduct genome-wide association studies meta-analyzing in trusted research environments or pooling together and find similar, but not identical results.

By inferring the cellular landscape of the neocortex in 638 aged individuals from RNA profiles, the authors uncovered unique cellular communities composed of coordinated populations of multiple cell types, which were altered in Alzheimer’s disease.

Behavioural studies and neural recordings in mice show that virgin mice can acquire maternal behaviour through an oxytocin-dependent mechanism.

The significance of rare and de novo variants in bipolar disorder is not well understood. Here, the authors have analyzed whole exome/genome data from trios to identify deleterious de novo variants associated with bipolar disorder.

Montserrat Garcia-Closas and colleagues report a genome-wide association study for bladder cancer. They identify three new susceptibility loci on chromosomes 22q13.1, 19q12 and 2q37.1.

Here, the authors design a multiplex serology platform to quantitatively measure antibodies against 20 infectious agents in UK Biobank participants and confirm associations of antibody responses with sociodemographic characteristics, HLA genetic variants, and disease outcomes.

After infection with SARS-CoV-2, individuals show a greater reduction in grey matter thickness and tissue contrast in the orbitofrontal cortex and parahippocampal gyrus; greater changes in markers of tissue damage in regions that are functionally connected to the primary olfactory cortex; and a greater reduction in global brain size.

An investigation using various methods reports an association between adeno-associated virus 2 and paediatric hepatitis of unknown aetiology.

Fishing has had a profound impact on global reef shark populations, and the absence or presence of sharks is strongly correlated with national socio-economic conditions and reef governance.

Non-human primates are important animal models for studying SARS-CoV-2 infection. Here, Salguero et al. directly compare rhesus and cynomolgus macaques and show that both species represent COVID-19 disease of mild clinical cases, and provide a lung histopathology scoring system.

SARS-CoV-2 induces mild infection in ferret model. Here, Ryan et al. characterise optimal infection dosage inducing upper respiratory tract (UTR) viral shedding, progression time of viral shedding, and pathology in ferrets and finally provide evidence for protection after re-challenge.

Two doses of the coronavirus disease 2019 vaccine ChAdOx1 nCoV-19 boost antibody responses and functions in phase 1/2 trial participants.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

SF3B1 mutations confer sensitivity to poly (ADP-ribose) polymerase inhibitors (PARPi). Mechanistically, this is independent of homologous recombination repair and instead relies on a defective replication stress response due to a reduction of the cyclin-dependent kinase 2 interacting protein (CINP). PARPi treatment of SF3B1 mutant (SF3B1^MUT) tumors leads to replication stress induced by increased fork origin firing and culminates in cell cycle stalling.

In bacteria, the conserved trans-translation system serves as the primary pathway of ribosome rescue, but many species can also use alternative rescue pathways. Here the authors report that in B. subtilis, the rescue factor BrfA binds to non-stop stalled ribosomes, recruits RF2 but not RF1, and induces transition of the ribosome into an open active conformation.