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The last universal cellular ancestor (LUCA) is the most recent population of organisms from which all cellular life on Earth descends. In this Perspective article, Krupovic, Dolja and Koonin analyse the extant distribution of viruses across the two primary domains of life to infer the LUCA virome.

Analysis combining multiple global tree databases reveals that whether a location is invaded by non-native tree species depends on anthropogenic factors, but the severity of the invasion depends on the native species diversity.

Estimates from the Global Burden of Disease study reveal declines in chronic respiratory disease mortality between 1990 and 2023—especially during the COVID-19 pandemic—but the burdens on people affected remain substantial.

Identifying jets originating from heavy quarks plays a fundamental role in hadronic collider experiments. In this work, the ATLAS Collaboration describes and tests a transformer-based neural network architecture for jet flavour tagging based on low-level input and physics-inspired constraints.

A multiancestry phenome-wide analysis of copy number variants in the UK Biobank genomes increases power to detect genetic associations with complex traits across human populations.

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.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

Functional studies of pathogenetic FLVCR1 variants associated with sensory neuropathy reveal that impaired choline uptake, heme biosynthesis, and ER–mitochondria Ca²⁺ transfer result in mitochondrial energetic failure.

Evolutionary modelling and expert review are applied to integrate experimentally supported knowledge accumulated in the Gene Ontology knowledgebase to create a draft human gene ‘functionome’.

This study associates p53 loss and brain metastasis in breast cancer. Mechanistically, p53-null tumors recruit astrocytes that provide substrates for enhanced fatty acid synthesis via upregulated SCD1 expression, representing a targetable axis in the disease.

EGF-induced recruitment of UPF1 adjacent to HNRNPC induces splicing surveillance of cell proliferation mRNAs.

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.

Early high-resolution images of two 2021 novae reveal eruptions unfolding in multiple stages with colliding outflows that produce shocks and gamma rays, reshaping our understanding of stellar explosions.

The authors describe the structure and function of two evolutionarily diverged RNA polymerases of a thermophilic phage. One of the polymerases is fused to the phage tape measure protein, a virion component dictating the length of the phage tail.

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.

Virus-like particles are engineered to edit human hematopoietic cells in vivo.

Species’ traits and environmental conditions determine the abundance of tree species across the globe. Here, the authors find that dominant tree species are taller and have softer wood compared to rare species and that these trait differences are more strongly associated with temperature than water availability.

Whole-genome sequencing in a Canadian cohort of 327 children with cerebral palsy compared to pediatric controls identifies novel pathogenic single-nucleotide variants/indels and copy number variations. In addition, mitochondrial variants in known disease genes were identified. This highlights the importance of genomic testing for individuals with cerebral palsy.

Systematic analysis from the Global Burden of Disease study reported that, despite global improvements from 1990 to 2021, dietary iron deficiency-associated disease burden remains high in women, children and residents in low socio-demographic index countries.

Research into steatotic liver disease should prioritize person-centred care and work towards a reduced disease burden and lower economic and societal costs.

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.

A genome-wide study by the Long COVID Host Genetics Initiative identifies an association between the FOXP4 locus and long COVID, implicating altered lung function in its pathophysiology.

Here the authors use a range of approaches to examine the interplay between genetic variants linked to risk for polygenic skin diseases and transcription factors (TFs) important for skin homeostasis. The findings implicate dysregulated binding of specific TF families in risk for diverse skin diseases.

Epigenetic regulators have been proposed to be modulators of chemoresistance in acute lymphoblastic leukaemia. Here, the authors find enrichment of mutations in epigenetic regulators at relapse, including somatic mutations in SETD2.

Owing to their ability to couple ion movement with ATP hydrolysis or synthesis, F-type and V-type ATPases constitute the cornerstone of cellular bioenergetics and are present in all three domains of life. In this Opinion, Eugene Koonin and colleagues use sequence and structural data to develop an evolutionary scenario for these ubiquitous molecular machines.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

The characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet-base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.

Analysis of ground-sourced and satellite-derived models reveals a global forest carbon potential of 226 Gt outside agricultural and urban lands, with a difference of only 12% across these modelling approaches.

Modern neutrino experiments require precise tuning of energy response parameters, a task complicated by the parameters’ nonlinear behavior and strong correlations. The authors present neural density estimators using normalizing flows and transformers integrating them with Bayesian nested sampling to achieve near-zero systematic biases and uncertainties limited only by statistics, offering a flexible framework for particle physics applications

Pancreatic cancer progression is driven by a switch from HNF4G-driven transcriptional activity in primary disease to FOXA1-mediated transcription in the metastatic setting.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

Wood density is an important plant trait. Data from 1.1 million forest inventory plots and 10,703 tree species show a latitudinal gradient in wood density, with temperature and soil moisture explaining variation at the global scale and disturbance also having a role at the local level.

In this Consensus Statement, an international panel of experts present an overview of the latest developments in the field of cholangiocarcinoma. A set of consensus recommendations and research priorities is provided.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

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.

This study presents a computational framework describing OCD frontostriatal dynamics, offering possible intervention targets to normalise functional brain activity and reduce symptom severity.

It is unclear whether naturally evolved de novo proteins have stable, folded structures. Here, systematic identification and structural modeling of de novo genes, this study reveals that a small subset of these proteins may have well-folded structures, and were likely born with these structures.

A device architecture based on indium arsenide–aluminium heterostructures with a gate-defined superconducting nanowire allows single-shot interferometric measurement of fermion parity and demonstrates an assignment error probability of 1%.

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 authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

The results obtained by seventy different teams analysing the same functional magnetic resonance imaging dataset show substantial variation, highlighting the influence of analytical choices and the importance of sharing workflows publicly and performing multiple analyses.

Designing effective dielectrics in a broad range of the spectrum is of huge interest. Here, the authors demonstrate how transparent effective dielectrics can be constructed from dense arrays of metallic nanoparticles and can result in being more transparent than real dielectrics renowned for their transparency.

A genome-wide association study of critically ill patients with COVID-19 identifies genetic signals that relate to important host antiviral defence mechanisms and mediators of inflammatory organ damage that may be targeted by repurposing drug treatments.

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.

Geospatial estimates of the prevalence of anemia in women of reproductive age across 82 low-income and middle-income countries reveals considerable heterogeneity and inequality at national and subnational levels, with few countries on track to meet the WHO Global Nutrition Targets by 2030.

The presence of classical type 1 dendritic cells (cDC1) positively influences prognosis in cancer, but their intricate networking with the various T cell types found in the tumour microenvironment is not fully appreciated. Here the authors show that cDC1 encounter with CD4⁺ helper T-cells transforms their gene expression signature, and these “helped” dendritic cells enable the function of anti-tumour cytotoxic T-cells.