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DNA-sequencing data from primary tumours and paired metastases from participants in the TRACERx lung study and PEACE autopsy programme are used to analyse the metastatic diversity of advanced non-small cell lung cancer and the seeding patterns that underpin it.

A single-cell spatial atlas identifies a B cell-predominant microenvironment within the profibrotic tubular niche that marks a subset of patients with diabetic kidney disease with rapid progression.

A large-scale study on the replicability of claims from social and behavioural science journals reports that about half of the results replicate in the same patterns as the original study.

Ageing impairs strategic re-aiming but enhances implicit recalibration during sensorimotor learning. The strategic deficit probably reflects reduced memory caching, whereas the implicit enhancement is linked to altered multisensory integration.

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.

Liu, Gad et al. develop an approach to purify the endoplasmic reticulum and integrate genetic, structural, molecular and cell biological analyses to identify SLC33A1 as an endoplasmic reticulum oxidized glutathione (GSSG) exporter in mammalian cells.

Endocrine-exocrine pancreas crosstalk is known to play a role in pancreatic ductal adenocarcinoma. Here, the authors discover that obesity induces the expression of the peptide hormone cholecystokinin (CCK) in β cells, affecting the peri-islet acinar cells and promoting islet-proximal tumor formation.

GLP-1–GIP–lanifibranor, a single-molecule agonist of GLP-1R, GIPR, PPARα, PPARγ and PPARδ, shows promising therapeutic efficacy against obesity-linked metabolic dysfunction in vitro and in mouse models via synergistic incretin and PPAR activity.

Here, the authors show that the Saccharibacteria Nanosynbacter lyticus strain TM7x elicits limited immune activation in the oral cavity, and binds to gingival epithelial cells via a T4P-dependent mechanism, leading to clustering of TLR2 receptors and subsequent caveolin-mediated endocytosis.

Phylogeographic analysis and ecological niche modelling identify environmental factors associated with dispersal events, range expansion and local circulation risk of Oropouche virus in people in Brazil.

A multicountry cohort study found that prediction models combining clinical parameters with either pulse oximetry or the host biomarker sTREM1 more accurately identified febrile children needing referral than standard WHO criteria.

Combining a computational framework and optogenetic and chemogenetic manipulations within and downstream of the cortico-basal ganglia circuit identifies the specific cortico-basal ganglia synapses that drive the acquisition and expression of rapid vocal changes during juvenile song learning.

This study shows that TE, an inferotemporal (IT) cortex subregion, displays stronger neural plasticity than TEO, another IT subregion, during learning of a challenging visual categorization task in primates, to which both areas contribute.

Wang et al. find that leukaemic stem cells preferentially localize to the metaphysis bone marrow niche and lose stemness when mobilized to the central marrow. Targeting DPP4–CXCL12–GPC3 disrupts this niche and enhances leukaemia treatment.

The transmission dynamics of the 2023–2024 Oropouche virus (OROV) outbreak in Brazil (Manaus City) revealed a twofold increase in Oropouche seroprevalence in Manaus, and in a separate historical reconstruction, the authors estimate that there were approximately 9.4 million OROV infections during major outbreaks across Latin America and the Caribbean.

Saturation genome editing of RNU4-2 identifies the functional and clinical impact of variants across the entire gene and delineates variants that cause a new recessive neurodevelopmental disorder distinct from ReNU syndrome.

The evolutionary dynamics of aneuploidy in solid tumors are challenging to study. Here the authors introduce a method, ALFA-K, which estimates karyotype fitness and predicts emergent karyotypes before experimental detection, and test its performance on synthetic and empirical data.

A delayed booster of Ebola vaccine induces a stronger and durable antibody response with higher affinity maturation than a single dose, providing long-lasting immunity and enhancing the ability to prevent and control Ebola disease.

Analysis of the somatic and transcriptomic profile of 123 acral melanoma samples from Mexican patients helps understand tumour origins and prognosis, and highlights the importance of including samples from diverse ancestries in cancer genomics studies.

A pangenome reference for the phenotypically diverse crop sorghum aims to help accelerate future efforts to breed crops that are better adapted to changing environments.

Divergent white matter metabolic patterns reveal a mechanistic basis for cognitive resilience and enhance prediction of future cognitive decline beyond established aging and dementia biomarkers.

Higher-order interactions are shown to contribute to the decrease in species diversity from low to high latitudes in global forests, potentially explaining why this intricate phenomenon cannot be adequately explained by pairwise interactions alone.

In this atlas paper, the authors provide a transcriptomic and spatial taxonomy of myeloid cells in the central nervous system of mice and humans in health and pathology.

WGS data were used from 347,630 individuals with European ancestry in the UK Biobank to obtain high-precision estimates of coding and non-coding rare variant heritability for 34 complex traits and diseases.

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.

Results of the phase 2 POLAR trial show that biomarker-guided treatment in patients with metastatic pancreatic cancer based on homologous repair deficiency leads to encouraging clinical response rates in immune cell-infiltrated tumors.

The fetal globin gene repressors BCL11A and ZBTB7A directly bind γ-globin gene promoter regions. Repressor binding is disrupted by naturally occurring point mutations located upstream of the transcriptional start site that are associated with hereditary persistence of fetal hemoglobin.

Navigational affordances describe our ability to identify routes of egress within scenes. Here, the authors show that this process likely occurs in early dorsal visual cortex and that such navigational affordances can emerge following brief presentation times.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

Stratified medicine promises to tailor treatment for individual patients, however it remains a major challenge to leverage genetic risk data to aid patient stratification. Here the authors introduce an approach to stratify individuals based on the aggregated impact of their genetic risk factor profiles on tissue-specific gene expression levels, and highlight its ability to identify biologically meaningful and clinically actionable patient subgroups, supporting the notion of different patient ‘biotypes’ characterized by partially distinct disease mechanisms.

Computational methods can be used to find potent neutralizing antibodies against viruses such as SARS-CoV-2. Here the authors use an AI method to landscape antibodies, predict specificity and antibody-antigen structure, pick out potent neutralizers and show that these antibodies are protective against SARS-CoV-2 challenge in mice models.

For calorie-restriction-adapted King penguins, living a sedentary life at the zoo increases life expectancy; but by suppressing metabolic challenges, it also accelerates the epigenetic markers of ageing, decoupling lifespan from health.

Desmoplastic small round cell tumor (DSRCT), a very rare and understudied sarcoma, presents serious challenges for both diagnosis and treatment. Here, the authors employ multi-omics profiling on 30 refractory DSRCT patients to improve the diagnosis and identify potentially actionable targets for individualized DSRCT treatment.

A global synthesis of >600 studies finds that across agro-ecosystems, grasslands and forests in temperate and tropical zones, increasing plant diversity has a consistently positive effect on plant performance and the suppression of antagonists.

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.

Climate and land-use change are transforming biodiversity, yet national futures remain uncertain. The study projects growing extinction debts, but suggests that sustainable low-emission pathways can limit the worst impacts on British biodiversity.

A study in rats proposes a mechanism for how the brain maps the surrounding environment, including places it has never seen, by alternating left and right forward sweeps in successive theta cycles.

cSplotch compares spatial transcriptomics data across ages and regions of mouse colon tissue.

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.

Shotgun metagenomic sequencing (using the MinION platform) of mock microbial communities and faecal samples from healthy and ill preterm infants can be used to identify pathogens and their antimicrobial resistance gene profiles in real time, indicating the potential for translation into clinical settings.

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

Resistance to first line treatment is a major hurdle in cancer treatment, that can be overcome with drug combinations. Here, the authors provide a large drug combination screen across cancer cell lines to benchmark crowdsourced methods and to computationally predict drug synergies.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

This study introduces the Lipid Nanoparticle Database (LNPDB) and web tool that consolidates lipid nanoparticle structure-function data. LNPDB facilitates molecular dynamics and deep learning approaches to advance data-driven design for nucleic acid delivery.

Stable isotope analysis of zooarchaeological remains and pottery in a palaeo-environmental framework reveals that early Central European farmers utilized diverse regional pasturing strategies for cattle, including the use of forested environments for grazing and seasonal foddering.

Seguin et al. show that the efficacy of transcranial magnetic stimulation for depression depends on how stimulation spreads through the brain’s wiring. Patients with shorter communication pathways between stimulated sites and mood-related regions had better clinical outcomes.

How is specific ribosomal RNA expression precisely controlled in the malaria parasite? Dr. Couble et al. show that a switch between distinct energy-generating pathways during parasite development directly impacts the accessibility to rDNA chromatin.

Following spinal cord injury, gamified physical therapy that incorporates closed-loop vagus nerve stimulation can aid restoration of arm and hand function.