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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).

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.

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.

Here, the authors examine the mechanisms behind cheatgrass’s successful invasion of North American ecosystems. Their genetic analyses and common garden experiments demonstrate that multiple introductions and migrations facilitated cheatgrass local adaptation.

Using well-calibrated statistical methods the authors jointly analyze Undiagnosed Diseases Network genomes, identifying known and novel disease genes. Software is publicly available to support future cross-cohort rare disease discovery efforts.

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.

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.

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.

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.

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.

Zhou, Novak and colleagues identify that the Caenorhabditis elegans hypodermis, a peripheral liver-like metabolic tissue, regulates memory via insulin/IGF-1 and Notch signaling, and show that activating this pathway rescues CREB-dependent memory in aged worms.

Transcriptomic and proteomic profiling of blood samples from individuals with COVID-19 reveals immune cell and hematopoietic progenitor cell alterations that are differentially associated with disease severity.

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.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

Remotely sensed NDVI data and contemporary field data from 84 grasslands on 6 continents show increasing divergence in aboveground plant biomass between sites in different bioclimatic regions.

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.

The Omicron variant evades vaccine-induced neutralization but also fails to form syncytia, shows reduced replication in human lung cells and preferentially uses a TMPRSS2-independent cell entry pathway, which may contribute to enhanced replication in cells of the upper airway. Altered fusion and cell entry characteristics are linked to distinct regions of the Omicron spike protein.

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.

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.

This overview of the ENCODE project outlines the data accumulated so far, revealing that 80% of the human genome now has at least one biochemical function assigned to it; the newly identified functional elements should aid the interpretation of results of genome-wide association studies, as many correspond to sites of association with human 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.

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.

Following progression on HER2-targeted first-line regimens, there are limited HER2-targeted therapies that have demonstrated efficacy in patients with gastroesophageal adenocarcinoma (GEA). Here, the authors report the results of a phase 1 clinical trial investigating zanidatamab (a HER2-targeted bispecific antibody) in heavily pre-treated patients with advanced or metastatic, HER2-expressing GEA.

Repeated evolution provides valuable insight into adaptation. In this study, the authors found that repeated evolution of cave-adapted phenotypes of a fish (Astyanax mexicanus) was driven by selection on standing genetic variation and novel mutations and genes repeatedly under selection are longer compared to the rest of the genome.

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

A genetic study of problematic alcohol use in 435,563 individuals, including data from the Million Veteran Program, Psychiatric Genomics Consortium and UK Biobank, found many novel risk loci and provided new insights into trait biology.

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.

Tiling describes the arrangement of neuronal processes in a pattern with little or no overlap with those of neighboring neurons. It is unclear how this is mediated in the vertebrate retina, whose mosaic cell body distribution of horizontal cells is accompanied by extensively overlapping dendrites. A study by Huckfeldt et al. now shows that the nonrandom distribution of the horizontal cells is correlated with repulsive homotypic interactions between developmentally transient processes, leading to the development of initial territories of horizontal cell.

This report describes a 3D microelectrode array integrated on a thin-film flexible cable using traditional thin-film processing techniques and direct laser writing of 3D structures at micron resolution via two-photon lithography for neural recording.

Here the authors apply machine learning approaches to Alzheimer’s genetics, confirm known associations and suggest novel risk loci. These methods demonstrate predictive power comparable to traditional approaches, while also offering potential new insights beyond standard genetic analyses.

Kranzler et al. examine the association between adverse childhood events and mood and anxiety disorders and substance dependence. The results show that adverse childhood events are associated with risk of substance dependence, with this effect mediated by mood and anxiety disorders. Similar associations were found for the risk of mood and anxiety disorders with substance dependence as a mediator.

Known genetic loci account for only a fraction of the genetic contribution to Alzheimer’s disease. Here, the authors have performed a large genome-wide meta-analysis comprising 409,435 individuals to discover 6 new loci and demonstrate the efficacy of an Alzheimer’s disease polygenic risk score.

Circulating tumour DNA profiling in early-stage non-small-cell lung cancer can be used to track single-nucleotide variants in plasma to predict lung cancer relapse and identify tumour subclones involved in the metastatic process.

Changes in semen quality over the last 50 years correspond with increasing environmental stressors. Here, Moon et al. causally identified stress-mediated changes in secreted extracellular vesicles as regulators of sperm motility in mice and men.

The expression of each of the roughly 22,000 genes of the mouse genome has been mapped, at cellular resolution, across all major structures of the mouse brain, revealing that 80% of all genes appear to be expressed in the brain.

An integrated analysis of de novo and inherited coding variants in 42,607 individuals with autism spectrum disorder identifies 60 risk genes of which five have not previously been associated with neurodevelopmental disorders.

Most bacteria exist in dense aggregates, yet this lifestyle is relatively poorly understood compared with planktonic cultures. This Review explores biophysical models of aggregate development, and how models can be extended to account for the complex behaviours of single-species and multispecies colonies.

Human brain structure changes throughout the lifespan. Brouwer et al. identified genetic variants that affect rates of brain growth and atrophy. The genes are linked to early brain development and neurodegeneration and suggest involvement of metabolic processes.

DNase I footprinting in 41 cell and tissue types reveals millions of short sequence elements encoding an expansive repertoire of conserved recognition sequences for DNA-binding proteins.

Cells from embryonic, fetal, paediatric and adult human intestinal tissue are analysed at different locations along the intestinal tract to construct a single-cell atlas of the developing and adult human intestinal tract, encompassing all cell lineages.