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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).

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.

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 authors present a multiomics study of type 2 diabetes and quantitative blood lipid and lipoprotein traits in Hispanic/Latino populations. They demonstrate how integrating GWAS with omics characterization can advance precision medicine.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

Large genome-wide meta-analysis of clinically diagnosed late-onset Alzheimer’s disease (LOAD) from 94,437 individuals identifies new LOAD risk loci and implicates Aβ formation, tau protein binding, immune response and lipid metabolism.

Whole-genome sequencing in a Canadian cohort of 327 children with cerebral palsy compared to pediatric controls identifies novel pathogenic single-nucleotide variants/indels and copy number variations. In addition, mitochondrial variants in known disease genes were identified. This highlights the importance of genomic testing for individuals with cerebral palsy.

Multi-ancestry genome-wide analyses identify 95 loci associated with post-traumatic stress disorder and implicate candidate genes, pathways and neurobiological systems underlying its pathophysiology.

Unraveling the signaling dependencies of EMLK4-ALK fusion–driven lung cancer reveals upfront combination therapy strategies.

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

Leidal et al. show that the LC3-conjugation pathway, which is part of the autophagy machinery, controls extracellular vesicle cargo loading and secretion of RNA-binding proteins.

Kelly et al. describe two cerebellum–thalamus–mPFC pathways in mice that regulate social and repetitive behavior. PC activation in Rcrus1 and posterior vermis improved social and reduced repetitive behaviors, respectively, in PC-Tsc1 mutant mice.

Perceptual abilities can be improved by training, up to certain limits. Martin et al. show that vagus nerve stimulation in mice boosts performance on an auditory task via cholinergic modulation, beyond the level achieved by training alone.

Cerebellar right Crus I (RCrusI) has been implicated in autism spectrum disorder (ASD). RCrusI modulation altered RCrusI–inferior parietal lobule connectivity, and this connectivity was atypical in children with ASD and in a TscI mouse model of ASD. Inhibition of RCrusI in mice led to autism-related behaviors, and RCrusI activation rescued social impairments in TscI mice.

Anti-cancer treatment often results in a subset of the clonal cell population developing resistance to therapy, with resistant cells displaying a diversity of fate types resulting from the intrinsic variability among the clonal population before treatment.

Metal–organic framework capture materials could reduce the environmental impact of SO₂ emissions but can have limited stability and poor reversibility. Here, a metal–organic framework with open Cu(ii) sites with fully reversible SO₂ uptake of 17.5 mmol g⁻¹ under ambient conditions is reported.

Genome-wide analyses identify common variants associated with 11 distinct neuropathology endophenotypes, providing insights into the mechanisms underlying the genetic risk of Alzheimer’s disease and related dementias.

Increased carbon dioxide levels, in combination with global warming, are predicted to lead to widespread impacts on marine ecosystems. Now research shows that the negative effects of ocean acidification and warming on juvenile fish are absent or reversed when parents also experience high carbon dioxide concentrations and warmer waters.

RNA alternative splicing is involved in determining cell identity, but a comprehensive molecular map is missing. Here, the authors provide a human and mouse brain atlas of transcript isoforms linking them to cellular identity, brain regions and development stages.

Complete RNA isoforms are captured by a new single-nuclei sequencing method.

Sven van der Lee, Julie Williams, Gerard Schellenberg and colleagues identify rare coding variants in PLCG2, ABI3 and TREM2 associated with Alzheimer's disease. These genes are highly expressed in microglia and provide additional evidence that the microglia-mediated immune response contributes to the development of Alzheimer's disease.

The One Thousand Plant Transcriptomes Initiative provides a robust phylogenomic framework for examining green plant evolution that comprises the transcriptomes and genomes of diverse species of green plants.

Pathologically altered stromas are a common contributing factor to cancer progression and fibrogenesis. This report uncovers the role of LOXL2 in the creation and maintenance of the pathological microenvironment of human cancers and fibrotic diseases and presents the development of a LOXL2-specific antibody that shows therapeutic activity in tumor as well as lung and liver fibrosis models.

Tropical species are considered especially sensitive to climate change, but research now shows that a tropical reef fish can rapidly acclimate over multiple generations. Acute exposure to a 1.5 °C and 3.0 °C temperature rise decreased an individual’s ability to perform aerobic activities such as swimming or foraging by 15% and 30% respectively, but this did not occur when both parents and offspring were reared at the higher temperature.

The degree to which human societies have responded to past climatic changes remains unclear. Here, using a novel combination of approaches, the authors show how volcanically-induced suppression of Nile summer flooding led to societal unrest in Ptolemaic Egypt (305–30 BCE).

APOE is the major genetic risk factor for Alzheimer’s disease. In a large number of neuropathologically confirmed cases and controls, the impact of different APOE genotypes on Alzheimer’s dementia risk was greater than previously thought and APOE2 homozygotes had an exceptionally low risk.

A spatially extensive survey of lake CH₄ and CO₂ emissions in Arctic Alaska shows the source material to be primarily relatively young organic matter (up to about 3,500 years old). Contributions from ancient C sources were twice as large in fine textured sediments.

A machine-learning algorithm using electronic medical records and self-reported measures of stress at admission to the emergency department due to trauma can predict the risk and long-term trajectories of post-traumatic stress disorder in two independent cohorts.

Neuroscientists face increasing pressure to disseminate results and discuss their implications with the public. Illes and colleagues consider the challenges that they face and make specific recommendations for individuals and institutions to promote this process.

Gerard Schellenberg and colleagues report a genome-wide association study of late-onset Alzheimer's disease (LOAD), as part of the Alzheimer Disease Genetics Consortium. They identify common variants in MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 associated with LOAD.