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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).

Short‑read sequencing misses many early and repeat‑driven mutations. Here, the authors show that long‑read sequencing in autism families increases detection of germline and postzygotic mutations and reveals high mutability in segmental duplications, especially in early embryos.

Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic.

Frenster et al. utilize mosaic mouse gastruloids as a model of cell fitness and competition, identifying a temporal window between primed pluripotency and early gastrulation during which cell competition occurs in mammalian embryogenesis.

METALoci, a new three-dimensional genome computational tool, reveals a major rewiring of regulatory interactions during sex determination. By combining this method with transgenic models, the authors identify a noncoding regulatory region at the Fgf9 locus and reveal that Meis genes are key regulators of sexual differentiation.

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.

It is unclear whether the harsh abiotic conditions of drylands hinder biological invasions. This global analysis shows that drylands are vulnerable to non-native plants and are likely to become more so as native plant diversity declines and grazing pressure intensifies.

Genome-wide association meta-analysis identifies 58 independent risk loci for major anxiety disorders among individuals of European ancestry and implicates GABAergic signaling as a potential mechanism underlying genetic risk for these disorders.

Rice paddies contribute to atmospheric methane (CH₄) levels. Here the authors show that increasing levels of the rice plant hormone PSY can reduce CH₄ emissions by over 50% via alteration of microbial H₂ cycling in the rhizosphere.

Microhomology-mediated end joining (MMEJ) and mitotic DNA synthesis (MiDAS) are critical DNA repair pathways in mitosis. Here the authors show that CIP2A–TOPBP1 coordinate mitotic DNA repair through the regulation of factors required for MiDAS and MMEJ.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

Trained on large and multicenter datasets with different imaging modalities, a foundation model is shown to have strong performance on the full spectrum of clinically relevant tasks and to increase user accuracy in diagnostic tasks.

The authors synthesize bee assemblage data from 681 crop fields across three continents, finding that local pesticide hazards and decreasing adjacent semi-natural habitats both negatively affected wild bee abundance and species richness in crop fields, while pesticides also reduced functional diversity.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

The study shows that rising life expectancy has masked the impact of climate change on heat-related mortality in Germany. It highlights the need to consider non-climatic factors underlying vulnerability in attribution studies of health outcomes.

Genotype and exome sequencing of 150,000 participants and whole-genome sequencing of 9,950 selected individuals recruited into the Mexico City Prospective Study constitute a valuable, publicly available resource of non-European sequencing data.

Despite frequent AKT/mTOR pathway activation in patient’s rhabdomyosarcoma (RMS), success of AKT inhibitors in the clinical has been limited. Here, using RMS patient-derived models, the authors demonstrate that the efficacy of the AKT inhibitor, ipatasertib, is in part due to its off-target effects on PRKG1, identifying PRKG1 as a potential biomarker for ipatasertib response.

The authors spatially and functionally map innate lymphoid cells in the human female genital tract at homeostasis, uncovering tissue-specific and subset-specific distribution and functions, and rapid antiviral responses following HIV exposure.

α/β-hydrolase domain-containing protein 11 (ABHD11) is a mitochondrial hydrolase, and its expression in CD4 + T-cells has been linked to remission status in rheumatoid arthritis. Here the authors report that pharmacological inhibition of ABHD11 modulates T-cell effector function via increased 24,25-epoxycholesterol biosynthesis and subsequent liver X receptor activation.

Protection afforded by inorganic minerals is assumed to make mineral-associated organic carbon less susceptible to loss under climate change than particulate organic carbon. However, a global study of soil organic carbon from drylands suggests that this is not the case.

By using foraminifera-bound nitrogen isotopes, it is shown that, during two warm periods of the Cenozoic, oxygen-deficient zones contracted rather than expanded, suggesting that global warming may not necessarily lead to increased oceanic anoxia.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

The cellular atlas of Pristina leidyi reveals cell type diversity in adult annelids by single cell transcriptomics, discovering several novel cell types and suggesting a pluripotent stem cell signature associated with adult cell type differentiation

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

Here, the authors show that Listeria monocytogenes faecal carriage is common in healthy asymptomatic individuals and, together with mouse studies, they associate carriage with a specific microbiome signature.

The origin of primary plastids in an ancestor of Archaeplastida gave eukaryotes photosynthetic capabilities. This study used single-cell genomics and phylogenomics to infer the evolutionary origin of the plastid-lacking phylum Picozoa, a group of marine microbial heterotrophic eukaryotes, showing that they belong to the Archaeplastida and changing our understanding of plastid evolution.

Survey data collected across ten low-income and middle-income countries (LMICs) in Asia, Africa and South America compared with surveys from Russia and the United States reveal heterogeneity in vaccine confidence in LMICs, with healthcare providers being trusted sources of information, as well as greater levels of vaccine acceptance in these countries than in Russia and the United States.

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.

Fanconi Anemia (FA) is caused by deficiencies in DNA repair, making it hard to correct. Here the authors report a therapeutic base editing strategy to address two of the most prevalent FANCA mutations in patient hematopoietic stem and progenitor cells.

Time-resolved serial femtosecond crystallography at X-ray free-electron lasers is a powerful approach for studying macromolecular dynamics, but its widespread use is limited by high sample consumption. Here, the authors introduce a segmented-droplet mix-and-inject strategy at the European XFEL that reduces sample consumption by up to 97% while preserving the data quality required for time-resolved structural studies of the enzyme NQO1.

Less than a month after the sequence of the SARS-CoV-2 Omicron variant was first announced, a number of articles in Nature and Cell examine its immune evasion characteristics.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

In the first results from an ongoing global cancer screening data repository, screening program organization was better overall in Europe compared to other continents; however, there were substantial gaps in implementation across both high- and low-resource settings.

Up to 25% of patients with ALK-rearranged non-small cell lung cancer (NSCLC) experience disease progression within the first year of targeted therapy. This work reports a phase 2 trial investigating whether combining alectinib with bevacizumab can delay resistance mechanisms in advanced ALK-rearranged NSCLC.

Complete sequences of chromosomes telomere-to-telomere from chimpanzee, bonobo, gorilla, Bornean orangutan, Sumatran orangutan and siamang provide a comprehensive and valuable resource for future evolutionary comparisons.

Repeated evolution provides valuable insight into adaptation. In this study, the authors found that repeated evolution of cave-adapted phenotypes of a fish (Astyanax mexicanus) was driven by selection on standing genetic variation and novel mutations and genes repeatedly under selection are longer compared to the rest of the genome.

A consensus cell type atlas for the fly brain provides both an intellectual framework and open-source toolchains for brain-scale comparative connectomics.

Song et al. developed a computational tool to profile binding pairs between tumor-derived antigens and antibodies from high-throughput B cell receptor sequencing data, predicting response to immune-checkpoint inhibitor therapy and risk of adverse events.

Petroni et al. report that the infiltration of IL-17A-secreting γδ T cells in the tumor microenvironment coupled with the accumulation of immunosuppressive macrophages is associated with resistance to CDK4/CDK6 inhibition in HR⁺HER2⁻ breast cancer.

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.

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.

Combined analysis of new genomic data from 116 ancient hunter-gatherer individuals together with previously published data provides insights into the genetic structure and demographic shifts of west Eurasian forager populations over a period of 30,000 years.

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