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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.

Analysis of snRNA genes in individuals with rare disorders identifies de novo and recurrent variants in RNU5B-1 and RNU5A-1, in addition to previously unreported cases with pathogenic or likely pathogenic variants in RNU4-2.

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.

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).

Post-infectious myalgic encephalomyelitis/chronic fatigue syndrome (PI-ME/CFS) is a disabling disorder, yet the clinical phenotype is poorly defined and the pathophysiology unknown. Here, the authors conduct deep phenotyping of a cohort of PI-ME/CFS patients.

Analysis of soundscape data from 139 globally distributed sites reveals that sounds of biological origin exhibit predictable rhythms depending on location and season, whereas sounds of anthropogenic origin are less predictable. Comparisons between paired urban–rural sites show that urban green spaces are noisier and dominated by sounds of technological origin.

Guidance is lacking on how to best integrate sex, gender and social and structural determinants of health into neuroscience research on brain resilience in ageing and dementia. In this Roadmap article, Rajah et al. propose a way forward for conducting more inclusive research in this field.

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.

Genome-wide ancient DNA data from individuals from the Middle Bronze Age to Iron Age documents large-scale movement of people from the European continent between 1300 and 800 bc that was probably responsible for spreading early Celtic languages to Britain.

Here the authors identify 33 individuals with a dominant neurodevelopmental disorder due to heterozygous missense or loss-of-function variants in the gene encoding Densin-180, a scaffold protein present at postsynaptic sites in neurons of the central nervous system.

Profiling the immune responses of 56 volunteers vaccinated with BNT162b2 reveals how this mRNA vaccine primes the innate immune system to mount a potent response to SARS-CoV-2 after booster immunization.

Computational search identifies dynobactin A which is a systemically active, natural-product peptide antibiotic that kills Gram-negative bacteria.

Adjuvants provide additional impetus for the immune response to vaccination regimens, however their modes of activity and impact on particular compartments of the immune response are currently not well understood. Here the authors perform high resolution assessment of the immune response to a well-established vaccination model and show innate immune transcriptomic and epigenomic alterations of innate cells in the lymph nodes following vaccination.

Despite effective vaccines against SARS-CoV-2, therapeutic options such as anti-virals and neutralizing antibodies are critical in treating disease, especially given the breakthrough infections of emerging VOCs. Here, Peng et al. generate two potent monoclonal antibodies and a bispecific antibody with two antigenrecognition variable regions targeting SARS-CoV-2 spike, provide CryoEM structures and show in vitro and in vivo efficacy of a humanized antibody against wildtype virus and delta variant.

A study reports single-cell RNA-sequencing profiles for more than 1.6 million cell nuclei from 101 whole mouse embryos including 22 mutant and 4 wild-type genotypes, from one experiment.

Monitoring cellular adhesion in blood samples is of fundamental importance, but conventional approaches may not capture the full physiological complexity of microscale flow in living contexts. Here, the authors present motion blur microscopy and machine learning-based image analysis to study cell interactions in microfluidic channels during whole blood flow.

Glycopeptide antibiotics are biosynthesized by non-ribosomal peptide synthetases, which contain a previously uncharacterized ‘X-domain’ now shown to recruit three cytochrome P450 oxygenases that are necessary for the antibiotics to achieve their final, active conformation.

Satellite carbon monoxide observations show that carbon emissions from the 2023 Canadian forest fires are comparable to the annual fossil fuel emissions of large nations.

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.

A phase I trial of cerebellar deep brain stimulation to enhance chronic post-stroke motor rehabilitation supports the safety and feasibility of the approach while providing encouraging evidence of motor improvements.

Macrophages mediate the fibrotic response after a heart attack by extracellular matrix turnover and cardiac fibroblasts activation. Here the authors identify an evolutionarily-conserved function of macrophages that contributes directly to the forming post-injury scar through cell-autonomous deposition of collagen.

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.

Results of the TRACERx study shed new light into the association between body composition and body weight with survival in individuals with non-small cell lung cancer, and delineate potential biological processes and mediators contributing to the development of cancer-associated cachexia.

The inner layer of the mucus that covers our intestine is nearly sterile. Here, the authors show in mice that the outer mucus layer constitutes a unique microbial niche hosting bacterial communities with distinct proliferation rates and resource utilization activities.

Combining in situ nanoprobe techniques paves the way for gaining insights into structure-selectivity relations for electrocatalysts. Herein, the dynamic evolution of lattice strain in individual nanoparticles is directly visualized with nanoscale resolution in Cu-Ag tandem catalysts during the electrocatalytic conversion of CO2 into value-added chemicals.

The Pharma Proteomics Project generates the largest open-access plasma proteomics dataset to date, offering insights into trans protein quantitative trait loci across multiple biological domains, and highlighting genetic influences on ligand–receptor interactions and pathway perturbations across a diverse collection of cytokines and complement networks.

Major histocompatibility complex (MHC) loss of heterozygosity, allele-specific mutation and measurement of expression and repression (MHC Hammer) detects disruption to human leukocyte antigens due to mutations, loss of heterogeneity, altered gene expression or alternative splicing. Applied to lung and breast cancer datasets, the tool shows that these aberrations are common across cancer and can have clinical implications.

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.

Analyses of multiregional tumour samples from 421 patients with non-small cell lung cancer prospectively enrolled to the TRACERx study reveal determinants of tumour evolution and relationships between intratumour heterogeneity and clinical outcome.

Biallelic loss-of-function variants in FOCAD cause a syndromic form of pediatric liver disease by compromising the SKI messenger RNA surveillance pathway.

Recruitment of substrates to virulent bacterial type III secretion systems remains enigmatic. Here, a crystal structure reveals two binding sites between a secretion substrate in complex with its chaperone and the cytosolic domain of the export gate.

Mixed responses to targeted therapy within a patient are a clinical challenge. Here the authors show that TP53 loss-of-function cooperates with whole genome doubling which increases chromosomal instability. This leads to greater cellular diversity and multiple routes of resistance, which in turn promotes mixed responses to treatment.

Renal cancer accounts for 2.4% of all adult cancers and its incidence is increasing worldwide. Here, the authors carry out genome and transcriptome sequencing of clear cell renal cell carcinomas (ccRCCs) and highlight genomic aberrations and biological pathways underlying ccRCC tumorigenesis.

A normative digital atlas of fetal brain maturation produced using 1,059 optimal quality, three-dimensional ultrasound brain volumes from 899 fetuses presents a unique spatiotemporal benchmark from a large cohort with normative postnatal growth and neurodevelopment at 2 years of age.

A simulation study integrates existing artificial selection methods to develop a ‘top-down’ approach to engineering complex, stable microbial communities based on iterated randomization and selection of community structure and function.

We present the ‘zebrafish single-cell atlas of perturbed embryos’, single-cell trancriptomic data of developing zebrafish embryos across various timepoints and with genetic perturbations.

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.

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.

Ancient proteins in human dental calculus from sites across Mongolia spanning 5,000 years suggest dairy consumption on the eastern Eurasian steppe by circa 3000 bc, and the later emergence of horse milking at circa 1200 bc, concurrent with the first evidence for horse riding.

Kubes and colleagues describe the presence in females of estrogen-driven, innate antibodies against specific oligosaccharides in EPEC that are maternally transferrable to offspring in mice and humans.

The early Eocene was characterized by exceptionally high global temperatures and no polar ice. Here, clumped isotope paleothermometry of glendonite calcite from the Danish Basin shows that these were formed in waters below 5 °C, indicating that regionalised cool episodes punctuated the background warmth of the early Eocene.

An HIV vaccine that elicits both antibodies and cellular immune responses confers long-lasting protection against viral challenge in nonhuman primates.

Analyses of the TRACERx study unveil the relationship between tissue morphology, the underlying evolutionary genomic landscape, and clinical and anatomical relapse risk of lung adenocarcinomas.