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AlphaGenome, a deep learning model that inputs 1-Mb DNA sequence to predict functional genomic tracks at single-base resolution across diverse modalities, outperforms existing models in variant effect prediction and enables comprehensive genomic analysis.

The CMS Collaboration reports the measurement of the spin, parity, and charge conjugation properties of all-charm tetraquarks, exotic fleeting particles formed in proton–proton collisions at the Large Hadron Collider.

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).

An extinct prehistoric plague lineage of Yersinia pestis has been documented from Central Europe to Asia during the Late Neolithic and Bronze Age. Here, Swali et al. show that this lineage spread to Europe’s northwestern periphery by sequencing three ~4000 year-old Yersinia pestis genomes from Britain.

The International Mouse Phenotyping Consortium (IMPC) aims to identify the function of all protein-coding genes in the mouse genome. Hayday and colleagues leverage 530 knockout lines from the IPMC to develop the 3i Project, which immunophenotypes mice and leads to the identification of new and unexpected gene influences on immune function and on the structural organization of the immune system.

Formaldehyde-preserved museum specimens have produced genetic data. Here, the authors generate chromatin profiles from museum specimens 117 years old and experimentally demonstrate chromatin profile presence in formalin-fixed mouse and yeast models.

The authors identify changes in insect distribution across Great Britain since 1990. The changes appear connected to insect traits, notably with species with multiple generations per year benefiting from increasing temperatures, particularly in the North.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

This study uses climate model experiments and shows that radiative heating from the presence of clouds can substantially increase the frequency of Euro-Atlantic atmospheric blocking, highlighting the need to better represent cloud-radiation interactions for improved prediction of extreme weather.

Living plant collections hold an immense wealth of plant diversity and have critical educational, scientific and conservation roles. This Perspective examines current data management practices of living collections and advocates for higher data standards and a robust and inclusive global data ecosystem.

Coordinated beating of motile cilia is important to clear mucus from the airway. Here, Clare et al. show that galectin-3 at the base of motile cilia in the trachea is important for connecting cortical microtubules to the basal body, and subsequent organization and coordination of beating cilia.

Parasitic nematodes causing onchocerciasis and lymphatic filariasis rely on a bacterial endosymbiont, Wolbachia, which is a validated therapeutic target. Here, Clare et al. perform a high-throughput screen of 1.3 million compounds and identify 5 chemotypes with faster kill rates than existing anti-Wolbachia drugs.

In this work, authors show that Salmonella uses its SPI-1 injectisome to infect macrophages, triggering rapid translational upregulation of transcription factors, such as EGR1 which suppresses the inflammatory response, aiding the bacteria in establishing systemic infection

During embryonic development, it is vital to maintain rapid genome duplication. Here, the authors shed light on the mechanism by revealing that SSRP1 stimulates replication origin assembly on somatic nuclei in Xenopus laevis egg extract by promoting histone H1 eviction from somatic chromatin.

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.

A post eradication polio vaccine should be safe and easy to produce. Here, the authors characterize a recombinant virus-like particle polio vaccine with stabilized capsid proteins and show comparable immunogenicity to the current inactivated polio vaccine.

Array microscope with mirrored well plates enables automated, scalable 3D behavioral analysis of 48 zebrafish larvae in parallel, revealing complex kinematics and phenotypes missed by conventional 2D methods.

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.

Dynamin mediates the fission of vesicles during endocytosis. Here, the authors report the cryoEM structure of a super-constricted two-start dynamin 1 filament- one of the two known helical forms of dynamin, with insights into the molecular mechanisms of dynamin-mediated membrane scission.

Here, the authors use single-cell spatial transcriptomics to profile the airway wall landscape in health and during asthma. Discrete proinflammatory ecosystems containing alarmins, chemokines and a unique combination of stromal cells were identified in healthy individuals, and these were spatially dysregulated in asthma.

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.

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.

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.

The quark structure of the f₀(980) hadron is still unknown after 50 years of its discovery. Here, the CMS Collaboration reports a measurement of the elliptic flow of the f₀(980) state in proton-lead collisions at a nucleon-nucleon centre-of-mass energy of 8.16 TeV, providing strong evidence that the state is an ordinary meson.

Despite observations from a hot-water-drilled access hole showing warm ocean waters beneath Thwaites Glacier Eastern Ice Shelf, the basal melt rate is strongly suppressed due to the low current speeds and strong density stratification.

Breast cancer leptomeningeal metastasis is difficult to assess due to the site. Here, the authors assess cerebrospinal fluid cell-free DNA to show specific mutations present in leptomeningeal metastasis, and develop organoids of the disease.

Multi-omics integration is often limited by data sparsity and heterogeneity. Here, the authors develop MOSA, a method designed to augment DepMap cell line data to synthetically generate multiomics data, increase efficacy of cell clustering and biomarker identification.

Resident microglia in the central nervous system are identified as the specific macrophage population that regulates myelin growth and integrity.

Understanding the ion intercalation and degradation mechanisms occurring during realistic battery operation is crucial to developing high-rate battery electrodes. Operando optical scattering microscopy is now used to study single-particle kinetic state-of-charge heterogeneities and cracking in high-rate Li-ion anode materials.

We show the evolution of a case of EGFR mutant lung cancer treated with a combination of erlotinib, osimertinib, radiotherapy and a personalized neopeptide vaccine targeting somatic mutations, including EGFR exon 19 deletion.

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.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

Using volumetric electron microscopy, the authors map and analyze the structure of cortical inhibition with synaptic resolution across a column of visual cortex.

The PSA (KLK3) genetic variant rs17632542 is associated with reduced prostate cancer risk and lower serum PSA levels, although the underlying reasons are unclear. Here, the authors show that this PSA variant reduced proteolytic activity and leads to smaller tumours, but also increases invasion and bone metastasis, indicating its dual risk association depending on tumour context; the variant is associated with both lower risk and poor clinical outcomes.

A genomic, transcriptomic and epigenomic analysis of chronic lymphocytic leukemia identifies genetic drivers and molecular subtypes associated with clinical outcomes.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

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.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

In this work, the authors describe immunisation of human antibody immune repertoire transgenic mice as a surrogate to define protective human antibody reactivity to clinically diverse, antibiotic resistant Acinetobacter baumannii.

5p and 3p miRNA strands have different mRNA-targeting sequences and may both functionally impact gene expression in cancer. Here, the authors undertake a pan-cancer analysis that indicates 5p/3p miRNA strands function together to regulate tumorigenic processes.

Primary colonization by microbial communities dominated by Bifidobacteria contribute to stable gut microbiota assembly and long-term pathogen resistance in neonates.

Cryo-electron microscopy is widely employed in structural biology and uses phase contrast imaging. Here, the authors employ electron ptychography, a quantitative phase retrieval method for high-contrast, low-dose phase imaging of cryo-state rotavirus and immature HIV-1 virus-like particles, and show that electron ptychography is more efficient for phase recovery than conventional phase contrast imaging.

The authors use Patch-seq and electron microscopy datasets to relate synaptic connectivity to the transcriptomic cell type of different types of inhibitory neuron.

Crowdsourced personal weather data are sought to cope with weather data scarcity. But, in England and Wales, more deprived areas are less covered. This limits the potential for climate adaptation of communities living in these environments.

Escherichia coli ST131 is a globally dominant multidrug resistant clone associated with high rates of recurring urinary tract infections. In this genomic epidemiology study, the authors describe the evolution, population structure, and antimicrobial resistance in 142 E. coli ST131 samples from Wales, UK.

Triple-negative breast cancers (TNBCs) are a heterogeneous group of cancers with varying prognoses. Here, the authors carry out whole-genome methylation capture sequencing from TNBC samples and matched normal samples, and identify differentially methylated regions that define a potentially novel TNBC signature.