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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.

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).

RNF213 is an E3 ligase with ATPase activity. Here, the authors show that RNF213 is activated by ATP binding and senses cellular energy states, and reveal a transthiolation mechanism induced by immune signals through ATP increase in macrophages.

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.

Integrated multi-omic analyses using samples from the TRACERx study highlight cross-talk between DNA hypermethylation and genomic lesions in non-small cell lung cancer.

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.

Short laser pulses of femtosecond time scales are in high demand in order to explore the fast electron dynamics in light-matter interactions. Here, the authors demonstrated the compression of free electron laser pulses in the extreme ultraviolet range by using a chirped pulse amplification technique.

Cortex morphology varies with age, cognitive function, and in neurological and psychiatric diseases. Here the authors report 160 genome-wide significant associations with thickness, surface area and volume of the total cortex and 34 cortical regions from a GWAS meta-analysis in 22,824 adults.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

Researchers observe Anderson localization for pairs of polarization-entangled photons in a discrete quantum walk affected by position-dependent disorder. By exploiting polarization entanglement of photons to simulate different quantum statistics, they experimentally investigate the interplay between the Anderson localization mechanism and the bosonic/fermionic symmetry of the wave function.

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.

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

Rainfall variability in Eastern Africa is associated with considerable social and environmental impacts, including threats to water, energy and food security. This Review outlines the drivers of this rainfall variability, their corresponding impacts, and potential future changes with anthropogenic warming.

A genome-wide association study of critically ill patients with COVID-19 identifies genetic signals that relate to important host antiviral defence mechanisms and mediators of inflammatory organ damage that may be targeted by repurposing drug treatments.

Uncertainty in estimates of future climate arises not only from internal variability, but also from model-to-model differences. Here, the authors use a new set of single model initial-condition large ensembles to quantify the contribution of model differences to the overall uncertainty in temperature and precipitation projections.

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.

Brian Fowler, David Rosenblatt and colleagues show that mutations in the ABC transporter gene ABCD4 cause a new inborn error of vitamin B₁₂ metabolism. ABCD4 colocalizes with the lysosomal proteins LAMP1 and LMBD1 and may be involved in intracellular processing of vitamin B₁₂.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

The non-coding RNA RNU4-2, which is highly expressed in the developing human brain, is identified as a syndromic neurodevelopmental disorder gene, and, using RNA sequencing, 5′ splice-site use is shown to be systematically disrupted in individuals with RNU4-2 variants.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

Transcriptomic analysis following epidural electrical stimulation of the lumbar spinal cord during neurorehabilitation in mice identifies a population of neurons that orchestrates the restoration of walking following paralysis.

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

Esophageal adenocarcinoma is characterised by frequent amplifications in oncogenes. Here, the authors use short- and long-read sequencing approaches to analyze primary tumor samples and tumour-derived organoids and to investigate the mechanisms underlying complex amplifications.

Kidney stones add colour to scientist's image.

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.

High ozone and low water structures in the tropical western Pacific are commonly attributed to transport from the stratosphere or mid-latitudes. Here, Anderson et al. show these structures actually result from ozone production in biomass burning plumes and large-scale descent of air within the tropics.

Both rare and common variants contribute to the aetiology of complex traits such as type 2 diabetes (T2D). Here, the authors examine the effect of coding variation on glycaemic traits and T2D, and identify low-frequency variation in GLP1Rsignificantly associated with these traits.

Whole-genome sequencing and phenotype data sharing are introduced in a national health system to streamline diagnosis and to discover coding and non-coding variants that cause rare diseases.

Extensive characterization of the stem and progenitor cell hierarchies of myelodysplastic syndromes reveals compensatory survival mechanisms underpinning the failure of hypomethylating agents, and uncovers biomarkers that predict second-line clinical response to venetoclax-based therapy.

Swanton and colleagues present a clonal expression signature, ORACLE, which, in combination with clinicopathological and molecular risk factors, can predict survival of patients with lung adenocarcinoma, and they prospectively validate its prognostic value.

The idea that autism and psychosis are two ends of a common spectrum is stirring up debate among geneticists and psychiatrists alike. It's controversial, but thanks to advances in comparative genomics, this hypothesis is now testable. Nicola Jones weighs the evidence.

Available evidence supports the existence of functional connections between resident microorganisms and the kidney that are altered in the context of specific kidney diseases. This Roadmap article describes current understanding of the mechanisms by which microorganisms regulate host organ function, highlighting key knowledge gaps that remain to be addressed and opportunities for future research.