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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.

This research investigates aperiodic neural activity in depressed individuals versus healthy controls using resting state electroencephalography recordings. Findings reveal significant differences in aperiodic exponent and offset, influenced by lifetime depressive episodes, highlighting the relationship between depression heterogeneity and neural mechanisms.

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 two independent knockout mouse models, the authors show that loss of Klhdc7b, a candidate for susceptibility to age-related hearing loss in humans, results in an early and progressive hearing loss, confirming Klhdc7b’s role in the maintenance of hearing.

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

Whole-genome sequencing analysis of individuals with primary immunodeficiency identifies new candidate disease-associated genes and shows how the interplay between genetic variants can explain the variable penetrance and complexity of the disease.

Combination of epidemiology, preclinical models and ultradeep DNA profiling of clinical cohorts unpicks the inflammatory mechanism by which air pollution promotes lung cancer

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.

Animals resolve uncertainty by seeking knowledge about the future. How the brain controls this is unclear. The authors show that a network including primate anterior cingulate cortex and basal ganglia encodes opportunities to gain information about uncertain rewards and mediates information seeking.

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.

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.

Jayavelu, Samaha et al., apply machine learning models on hospital admission data, including antibody titers and viral load, to identify patients at high risk for Long COVID. Low antibody levels, high viral loads, chronic diseases, and female sex are key predictors, supporting early, targeted interventions.

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.

The snow surrounding research facilities and shore tourist-landing sites in Antarctica was found to be darker than elsewhere in the continent, which suggests that local emissions of black carbon are accelerating seasonal snowmelt in impacted regions.

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.

Petrels are wide-ranging, highly threatened seabirds that often ingest plastic. This study used tracking data for 7,137 petrels of 77 species to map global exposure risk and compare regions, species, and populations. The results show higher exposure risk for threatened species and stress the need for international cooperation to tackle marine litter.

Patient-derived xenografts are important tools for cancer drug development. Here, the authors develop models from 22 non-small cell lung cancer patients. They show genomic differences between models created from different spatial regions of tumours and a bottleneck on model establishment.

This Viewpoint puts forward the intriguing hypothesis that vitamin K is a modifiable risk factor for vascular calcification in patients on dialysis. Reports linking vitamin K with regulation of vascular calcification via the actions of matrix GLA protein are set in the context of the authors' own data on the incidence of subclinical vitamin K deficiency and the use of the vitamin K antagonist warfarin in the dialysis setting.

Nearby small objects appear larger than distal large objects, reflecting a dissociation between perceived and actual object size. Collegio et al. show that inferences of true object size scale spatial attention to objects.

People can learn to identify a person based on their voice, despite variation in their voice. Here, the authors show that this ability relies on a statistical abstraction mechanism during which people form average-based representations of voices, even without prior exposure to the average.

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.

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.

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.

In lung adenocarcinoma, antibodies against endogenous retroviruses promote anti-tumour activity, and expression of endogenous retroviruses can predict outcomes of immunotherapy.

Like humans, songbirds learn to communicate vocally early in life. Moore and Woolley taught birds the songs of a different species to identify how vocal experience and auditory tuning mechanisms create neural representations of communication sounds.

Measurements of subclonal expansion of ctDNA in the plasma before surgery may enable the prediction of future metastatic subclones, offering the possibility for early intervention in patients with non-small-cell lung cancer.

A longitudinal evolutionary analysis of 126 lung cancer patients with metastatic disease reveals the timing of metastatic divergence, modes of dissemination and the genomic events subject to selection during the metastatic transition.

The Russian invasion of Ukraine has affected the global economy, environment, and political order. Here, the authors show that it also coincided with a temporary decline in psychological well-being across Europe.

Computational and machine-learning approaches that integrate genomic and transcriptomic variation from paired primary and metastatic non-small cell lung cancer samples from the TRACERx cohort reveal the role of transcriptional events in tumour evolution.

Analysis of whole-genome doubling (WGD) by using cancer sequencing data combined with simulations of tumor evolution suggests that there is negative selection against homozygous loss of essential genes before WGD but not after.

RNA sequencing data and tumour pathology observations of non-small-cell lung cancers indicate that the immune cell microenvironment exerts strong evolutionary selection pressures that shape the immune-evasion capacity of tumours.

The role of IgG glycosylation in the immune response has been studied, but less is known about IgM glycosylation. Here the authors characterize glycosylation of SARS-CoV-2 spike specific IgM and show that it correlates with COVID-19 severity and affects complement deposition.

Osteocalcin is a vitamin-K-dependent bone matrix protein that has been linked to glucose metabolism in mice. This finding presents a new paradigm for understanding the role of the skeleton and energy metabolism. This Review highlights the unique species-specific features of osteocalcin and the evidence for its role in energy metabolism in humans.

Epidemiological analyses coupled with immunological phenotyping suggest that humoral immunity induced by COVID-19 vaccines wanes more rapidly in individuals with severe obesity compared to individuals with a BMI within the normal range.

Age-associated B cells (ABC) have been shown to be associated with autoimmunity and ageing. Here the authors examine whether ABC are transcriptionally or functionally altered in participants with reduced immune cell function and show that, being transcriptionally similar, high pre-vaccine levels are associated with poor vaccine response.

Severe congenital development defects such as Jeune syndrome can result from the malfunction of primary cilia and dynein. Here Schmidts et al. report unique biallelic null mutations in a gene encoding a dynein light chain, helping to explain the nature of ciliopathies in human patients.

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.

Scott and colleagues show that expression of the transcription factor Sox9 is closely correlated with the transition from neuroepithelial cell to neural stem cell (NSC) during embryogenesis. Expression of Sox9 in early neuroepithelium elicited premature generation of NSCs. In the adult brain, Sox9 was necessary for the maintenance of NSCs and ependymal cells.

Integration of a probabilistic reversal learning task aligned between humans and rodents demonstrates concordant behavioral, computational, and neurophysiological measures of cognitive flexibility between species.

Vitamin D deficiency is associated with multiple human pathologic conditions. In a genome-wide association study of 79,366 individuals, Jiang et al. replicate four and identify two new genetic loci for serum levels of 25-hydroxyvitamin D and find evidence for a shared genetic basis with autoimmune diseases.

A robotically handled culture system using porcine gastrointestinal tissue explants for the high-throughput interrogation of the gastrointestinal tract predicts the absorption of oral drugs in the human gut better than Caco-2 Transwells.

It is known that exercise influences many human traits, but not which tissues and genes are most important. This study connects transcriptome data collected across 15 tissues during exercise training in rats as part of the Molecular Transducers of Physical Activity Consortium with human data to identify traits with similar tissue specific gene expression signatures to exercise.

A survey of T cell repertoire evolution in the tumors, healthy tissue and blood of patients with early-stage untreated lung cancer offers an opportunity to monitor and identify neoantigen-specific T cells for personalized immunotherapy.

In the TRACERx cohort of 171 patients with lung cancer, the ultrasensitive detection of ctDNA improves preoperative patient stratification, also in early-stage disease.

Yuan and colleagues developed an artificial intelligence-based method to derive growth patterns and morphological features from hematoxylin and eosin-stained slides of lung adenocarcinoma samples, for improved tumor grading and patient prognostication.