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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.

A report from the Australian Acute Care Genomics programme shows that the integration of rapid whole-genome sequencing and multi-omic analyses informs diagnoses and treatment decisions in a prospective cohort of 290 critically ill infants and children.

Post-acute sequelae of SARS-CoV-2 (PASC) is still not well understood. Here the authors provide patient reported outcomes from 590 hospitalized COVID-19 patients and show association of PASC with higher respiratory SARS-CoV-2 load and circulating antibody titers, and in some an elevation in circulating fibroblast growth factor 21.

The CMS Collaboration reports evidence for off-shell Higgs boson contributions in the production of Z boson pairs, and measures the width of the Higgs boson, which is inversely related to its lifetime.

This array-based discovery tool creates linkage between functional mutations and selectable markers across a bacterial genome and can thus distinguish between adaptive and neutral mutations.

The most up-to-date combination of results on the properties of the Higgs boson is reported, which indicate that its properties are consistent with the standard model predictions, within the precision achieved to date.

The CMS Collaboration reports the study of three simultaneous hard interactions between quarks and gluons in proton–proton collisions. This manifests through the concurrent production of three J/ψ mesons, which consist of a charm-quark–antiquark pair.

Late-life cognitive dysfunction is common, but the biological substrates are largely unknown. Here, the authors examined a panel of 90 neurology-related protein biomarkers and show that plasma levels of 22 of these proteins are associated with general fluid cognitive ability in later life.

Genome-wide association studies have identified regions which confer risk of high-grade serous epithelial ovarian cancer. Here the authors use expression quantitative train locus analysis to identify candidate genes and functionally characterise them, identifying a role for HOXD9 in ovarian cancer.

Solid organ transplant recipients are at increased risk of infectious disease and have unique molecular pathophysiology. Here the authors use host-microbe profiling to assess SARS-CoV-2 infection and immunity in solid organ transplant recipients, showing enhanced viral abundance, impaired clearance, and increased expression of innate immunity genes.

The impact of prior infection on the immune response to COVID-19 vaccination has not been fully characterised. Here, the authors use data from ~100,000 adults in the UK and find that a single vaccine dose in those with prior infection produces a comparable or stronger response to two doses in those without infection.

A catalogue of the vascular flora of New Guinea indicates that this island is the most floristically diverse in the world, and that 68% of the species identified are endemic to New Guinea.

Many genetic variants have been associated with human traits, but the mechanism is often unknown. Here, the authors integrate local and distal genetic associations with multi-omics datasets to provide a roadmap to understand the underlying mechanisms of GWAS variants on complex traits.

Experimental work in juvenile threespine sticklebacks shows that offspring from a single clutch display the same phenotypic and molecular responses to information on predation risk when this information is conveyed through paternal cues or personal experience.

Most people who are infected with SARS-CoV-2 seroconvert within a few weeks, but the determinants and duration of the antibody response are not known. Here, the authors characterise these features of the immune response using data from a large representative community sample of the UK population.

Simpson and colleagues systematically interrogate the influence of dietary carbohydrate type and quality on the obesogenic impact of protein-diluted diets in mice.

This study supports neurofilament light chain protein (NfL) in both cerebrospinal fluid (CSF) and blood as an early marker of neurodegeneration in Alzheimer’s disease but suggests that NfL in CSF may be better suited than blood for monitoring clinical trial outcomes in symptomatic patients.

The measurement of the total cross-section of proton–proton collisions is of fundamental importance for particle physics. Here, the first measurement of the inelastic cross-section is presented for proton–proton collisions at an energy of 7 teraelectronvolts using the ATLAS detector at the Large Hadron Collider.

The structure of peptide N-AcYTLDADF when bound to the large subunit of mouse ribonucleotide reductase has been elucidated by transfer NOE. This structure suggests a general design for type 1 RR inhibitors.

A randomized trial in patients hospitalized with COVID-19 showed no benefit and potentially increased harm associated with the use of convalescent plasma, with subgroup analyses suggesting that the antibody profile in donor plasma is critical in determining clinical outcomes.

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.

Several non-haematopoietic-cell-derived cytokines, including interleukin (IL)25, have been implicated in inducing T helper 2 (T_H2) cell-dependent inflammation, but their precise role has been unclear. Here, IL25 is shown to promote the accumulation of multipotent progenitor cells in gut-associated lymphoid tissue. These cells can give rise to macrophage or granulocyte lineages that promote the differentiation of T_H2 cells and contribute to protective immunity against helminth infections.

Multi-ancestry genome-wide analyses identify variants near UGT2A1 and UGT2A2 associated with COVID-19-related loss of smell or taste. Both genes are expressed in the olfactory epithelium and play a role in metabolizing odorants.

Turner and colleagues show that the RNA-binding protein ZFP36L1 regulates a post-transcriptional hub that determines the identity of marginal-zone B cells by promoting their localization and survival.

Gilean McVean and colleagues report the results of a large-scale clinical genome sequencing project spanning a broad spectrum of disorders. They identify factors influencing successful genetic diagnosis and highlight the challenges of interpreting findings for genetically heterogeneous disorders.

Whole-genome analysis of the elephant shark, a cartilaginous fish, shows that it is the slowest evolving of all known vertebrates, lacks critical bone formation genes and has an unusual adaptive immune system.

The formation of heterochromatin involves spreading of repressor proteins along large chromosomal domains. A new study reveals that the concept of spreading also holds true for establishing domains of active chromatin. More specifically, spreading of the Drosophila melanogaster male-specific lethal (MSL) activator complex, which is required for dosage compensation on the X chromosome, involves interaction between the MSL3 chromodomain and histone H3 methylated at lysine 36.

The factors influencing risk of reinfection with SARS-CoV-2 are poorly understood. Here, the authors use data from the UK COVID-19 Infection Survey, a community based longitudinal study, to assess characteristics of ~45,000 reinfections compared to initial infections.

A large study in the United Kingdom shows that virus-specific antibody levels associated with at least 67% protection against SARS-CoV-2 Delta variant infection last longer after two doses of BNT162b2 vaccine than after two doses of ChAdOx1 vaccine in previously uninfected individuals.

A study of more than one million 23andMe research participants identifies genetic and nongenetic associations with COVID-19 susceptibility and severity.

Patient-derived tumour organoids are important preclinical models but suffer from variability from the use of basement-membrane extract and cell contamination. Here, the authors report on the development of mimetic nanofibrilar hydrogel which supports tumour organoid growth with reduced batch variability and cell contamination.

Proteomic analysis of cerebrospinal fluid from individuals with autosomal dominant Alzheimer’s disease reveals how this complex and chronic disease evolves over many decades.

Quantum electrodynamics predicts a rare process in which light is scattered by light. The ATLAS Collaboration reports signs of this elusive effect in the collisions of ultra-relativistic lead ions.

Analysis of the imprinted KLF14 locus shows that the type 2 diabetes risk alleles in this region act in adipocytes to reduce KLF14 expression and modulate the expression of almost 400 genes in trans, leading to a shift in body-fat distribution and insulin resistance specifically in females.

Multi-ancestry genome-wide association analyses identify new risk loci for Parkinson’s disease, and fine-mapping and co-localization analyses implicate candidate genes whose expression is associated with disease susceptibility.

Growing evidence suggests that environmental rather than genetic factors are major contributors to asthma development. Here the authors show that high intake of dietary fibre by pregnant mice increases resistance of their progeny to the development of allergic airways disease.

Around 10% of high-grade serous ovarian carcinomas (HGSOC) harbor BRCA1 promoter methylation, but it is uncertain how it predicts response to PARP inhibition. Here, the authors show that homozygous BRCA1 methylation predicts response to rucaparib while heterozygous methylation of BRCA1 predicts resistance in HGSOC.

RNA-binding proteins are involved in post-transcriptional regulation. Turner and co-workers show that these proteins are also critical in thymopoiesis.

Alzheimer’s disease has been associated with increased structural brain aging. Here the authors describe a model that predicts brain aging from resting state functional connectivity data, and demonstrate this is accelerated in individuals with pre-clinical familial Alzheimer’s disease.

Primary open-angle glaucoma (POAG) is highly heritable, yet not well understood from a genetic perspective. Here, the authors perform a meta-analysis of genome-wide association studies in 34,179 POAG cases, identifying 44 previously unreported risk loci and mapping effects across multiple ethnicities.

A chemoproteomic approach adapted for high-throughput screening leads to the identification of a selective PI3Kγ inhibitor. Application of this inhibitor in human and mouse cellular models reveals a role for PI3Kγ in T_H17 cell differentiation.

That different people differ in their readiness to take risks is an obvious feature of human personality. Theoretical advances now help in making sense of observations of analogous behaviour in animals.

Behavioural traits can influence an individual animal's fitness, and trait combinations can change over its lifetime, according to a study of wild trout during a key period in their development.

The levels of 1,251 metabolites are measured in 475 phenotyped individuals, and machine-learning algorithms reveal that diet and the microbiome are the determinants with the strongest predictive power for the levels of these metabolites.