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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.

Reduced glomerular filtration rate (eGFR) is a hallmark of chronic kidney disease. Here, Pattaro et al. conduct a meta-analysis to discover several new loci associated with variation in eGFR and find that genes associated with eGFR loci often encode proteins potentially related to kidney development.

Vaccination is effective in protecting from COVID-19. Here the authors report immune responses and breakthrough infections in twice-vaccinated patients receiving anti-TNF treatments for inflammatory bowel disease, and find dampened vaccine responses that implicate the need of adapted vaccination schedules for these patients.

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

A multi-ancestry genome-wide gene–smoking interaction study identifies 13 new loci associated with serum lipids.

Infection with Omicron after vaccination produces cross-neutralizing antibodies to other variants of concern, whereas this induces a limited response to non-Omicron variants in unvaccinated individuals.

A region on chromosome 19p13 is associated with the risk of developing ovarian and breast cancer. Here, the authors genotyped SNPs in this region in thousands of breast and ovarian cancer patients and identified SNPs associated with three genes, which were analysed with functional studies.

Raman and fluorescence spectra, consistent with several species of aromatic organic molecules, are reported in the Crater Floor sequences of Jezero crater, Mars, suggesting multiple mechanisms of organic synthesis, transport, or preservation.

A retrospective analysis of primary care records in the United Kingdom reveals individual symptoms associated with SARS-CoV-2 infections, which persisted for 12 weeks or more after infection, as well as risk factors associated with developing long COVID.

CS-Rosetta-RNA is a web tool for determining high-resolution structures of noncoding RNA motifs using ¹H NMR chemical shift data coupled with Rosetta-based modeling.

Conversion of rainforest to plantations in Sumatra leads to higher energetic losses in animal food webs aboveground than belowground, with the belowground energy being reallocated from diverse arthropod communities to invasive earthworms.

For many neurodevelopmental disorder (NDD) risk genes, the significance for mutational burden is unestablished. Here, the authors sequence 125 candidate NDD genes in over 16,000 NDD cases; case-control mutational burden analysis identifies 48 genes with a significant burden of severe ultra-rare mutations.

The year 2014 marks the 50th anniversary of the discovery of protein acetylation. In this Timeline article, Verdin and Ott discuss the identification of this modification, of its regulatory enzymes and of the roles of acetylation in transcription and other cellular processes, and provide an outlook on the future of the field.

Ageing increases the risk of many diseases. Here the authors compare blood cell transcriptomes of over 14,000 individuals and identify a set of about 1,500 genes that are differently expressed with age, shedding light on transcriptional programs linked to the ageing process and age-associated diseases.

Conserved microbiome features across clinical and geographical variations may enable microbiome-based predictions of outcomes in CD19-targeted CAR-T cell immunotherapy

Cooperation is vulnerable to cheating, and both cooperation and cheating may be especially common in viruses. Here, Leeks et al. place diverse examples of viral cooperation and cheating within an evolutionary framework, highlighting opportunities emerging from greater synthesis of virology and evolutionary theory.

In this work, Danileviciute, Zeng et al. provide new insights into the regulation of the PDH complex by PARK7/DJ-1 and show its relevance in T_reg homeostasis during ageing.

The authors defined a roadmap for investigating the genetic covariance between structural or functional brain phenotypes and risk for psychiatric disorders. Their proof-of-concept study using the largest available common variant data sets for schizophrenia and volumes of several (mainly subcortical) brain structures did not find evidence of genetic overlap.

Thousands of plants are known to be edible, yet we lack nutritional data for many of them. This study predicts the B-vitamin profiles for edible plants and finds many have the potential to help alleviate deficiencies and should be conservation priorities.

Here, the authors characterize two distinct T_reg cell populations in the visceral adipose tissue of lean and high-fat diet-fed mice. ST2⁺ T_reg cells are dominant in male mice and are transcriptionally driven by GATA3 and PPARγ, regulators that limit the differentiation of the more female-dominant population of CXCR3⁺ T_reg cells that are T-bet dependent. Functional distinctions are also evident in glucose tolerance and adipose inflammation.

IL6-STAT3 signaling is activated in prostate cancer, however inhibiting this pathway has not lead to a survival advantage in patients. Here, Pencik et al.show that loss of the IL6-STAT3 axis in mice and humans leads to metastasis due to loss of ARF, unravelling STAT3 and ARF as potential prognostic markers in prostate cancer.

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

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.

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.

High contiguity human genomes can be assembled de novo in 6 h using nanopore long-read sequences and the Shasta toolkit.

The genome of the biofuel crop switchgrass (Panicum virgatum) reveals climate–gene–biomass associations that underlie adaptation in nature and will facilitate improvements of the yield of this crop for bioenergy production.

Metagenomic and metaproteomic analysis of soil from a 17-year tropical forest fertilization experiment supports the hypothesis that microbial communities respond to nutrient deficiency by enhancing the extraction of phosphorus from recalcitrant substrates.

A recent study has found that one in six people who are independent at 3 months after stroke deteriorate and need assistance by 12 months. Older women with comorbidities, and patients not given appropriate secondary stroke prevention were most at risk. Anticipation and prevention of deterioration could help reduce the later burden of stroke.

Primary biliary cirrhosis is an autoimmune liver disease with poor therapeutic options. Here Cordell et al. a perform meta-analysis of European genome-wide association studies identifying six novel risk loci and a number of potential therapeutic pathways.

Neuroinflammation is observed in Alzheimer’s disease. Here the authors show that 15 proteins related to inflammation found in CSF can potentially be used as a prognostic biomarker.

Defined levels of SARS-CoV-2-specific binding and neutralizing antibodies elicited by the COVID-19 vaccine ChAdOx1 nCoV-19 are identified as correlates of protection against symptomatic infection.

In this study the authors identify a possible link between the gene FAM222A and brain atrophy. The protein it encodes is found to accumulate in plaques seen in Alzheimer’s disease, and functional analysis suggests it interacts with amyloid-beta.

Thirteen pharmaceutical companies have shared and integrated preclinical and clinical data for creating computational resources that enhance translational drug safety assessment.