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ATF6α activation in human and preclinical models of hepatocellular carcinoma is significantly associated with an aggressive tumour phenotype characterized by reduced survival, glycolytic reprogramming and local immunosuppression.

This study uses brain recordings, self-reports, and facial analysis to decode acute pain in epilepsy patients. Machine learning reveals stable neural markers in mesolimbic, striatal, and cortical regions, plus facial cues, enabling reliable pain detection in naturalistic settings.

PARM is a deep-learning model trained on data from massively parallel reporter assays to help predict promoter activity in different human cell types, design synthetic promoters and identify key features of regulatory promoter grammar.

Systematic screening of transcription factors reveals conserved mechanisms governing cortical radial glia lineage progression across primates and provides a framework for functional dissection of gene regulatory networks in human cortical neurogenesis.

In Eastern Asia, vegetation greening, especially in perennial drylands, has increasingly reduced dust emissions since the early 2000s, with effects amplified over long timescales, underscoring the mitigating capacity of land-surface change for multi-decadal dust trends.

Saturation genome editing of a cancer mutation hotspot in CTNNB1, the gene encoding β-catenin, reveals a gradient of effects of missense mutations on Wnt signaling.

Plant traits drive ecosystem dynamics yet are challenging to map globally due to sparse measurements. Here, the authors combine crowdsourced biodiversity observations with Earth observation data to accurately map 31 plant traits at 1 km² resolution.

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.

The inter-individual variation of the immune system broadly impacts pathophysiology. Here, the authors use the hybrid mouse diversity panel as a surrogate for human natural immune variation and derive a macrophages gene signature robustly correlating with susceptibility to macrophage-related disorders in humans.

Jacquemyn et al. identify key lipid determinants controlling ectosome shedding from neurons. They find that ectosomes are a major route for the intercellular transport of misfolded α-synuclein, with relevance to Parkinson’s disease pathology.

Post-transcriptional regulation of mRNA translation was explored using Ribo-STAMP and single-cell RNA sequencing to reveal cell-type-specific and isoform-specific translation patterns across hippocampal neuronal and non-neuronal cell types, highlighting functional differences between CA1 and CA3.

How the brain supports speaking and listening during conversation of its natural form remains poorly understood. Here, by combining intracranial EEG recordings with Natural Language Processing, the authors show broadly distributed frontotemporal neural signals that encode context-dependent linguistic information during both speaking and listening..

Huang, Rigau and colleagues observe major changes in how DNA is organized in early germ cells before they start developing into sperm or eggs. These results show that germline removes structural ‘memory’ of DNA folding to start fresh for the next generation.

Here the authors perturb genes linked to schizophrenia risk in human neurons. They find that single perturbations share common downstream effects on gene networks, while joint perturbations result in downstream effects being saturated.

A model trained to generate spatial proteomics profiles and predict the expression of 40 biomarkers directly from histopathology slides is shown to improve survival and treatment response prediction in patients with lung cancer.

Single-cell technologies generate complex datasets, but effective cell alignment across studies—within and across modalities—remains challenging. Here, the authors introduce scGALA, a graph-based self-supervised framework that advances cell alignment to improve data integration and harmonization.

A comprehensive atlas platform integrating transcriptional and epigenetic data enables more precise engineering of T cell states, accelerating the rational design of more effective cellular immunotherapies.

Here natural language processing tools are used to systematically analyse 124 national food system pathway documents submitted by countries between 2021 and 2023, following the 2021 United Nations Food Systems Summit. Besides drawing out key themes, the authors reveal key issues that remain unaddressed.

Mucosal administration of a multivalent, adjuvanted vaccine against Clostridioides difficile promoted bacterial clearance and protected against morbidity, mortality, tissue damage and recurrence in mice.

A genetic study in over 300,000 males reveals that Y chromosome loss affects type 2 diabetes risk differently in East Asians and Europeans. Multi-omics data suggest that this may be due to impaired glucose metabolism in Y-deficient pancreatic β cells.

This research identifies two neural factors linked to externalizing and internalizing symptoms through a longitudinal imaging-genetic cohort. Distinct neural configurations and cognitive-behavioral relevance highlight the need for tailored therapeutic strategies addressing psychiatric comorbidity across developmental stages.

Kornfeld-Sylla et al reveal how alpha brainwaves are altered in children and adults with Fragile X Syndrome (FXS) and find parallel changes in alpha-like rhythms in juvenile and adult FXS model mice, showing their use for testing potential therapies.

Single-cell RNA sequencing and assay for transposase-accessible chromatin using sequencing profiling of human retinal samples from diverse ancestries create an epitranscriptomic atlas characterizing over 130 cell types. Integration with genome-wide association study and expression quantitative trait loci data provides further insights into gene regulation and disease etiology.

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.

Donahue et al. show that ageing is associated with changes in ER morphology. ER-phagy drives age-associated ER remodelling through tissue-specific factors.

Astrocytes in the basolateral amygdala dynamically track fear state and support fear memory retrieval and extinction.

The functions of the vast majority of brain-expressed spliced isoforms are unknown. Here the authors describe an isoform-resolution perturbation system coupled to a single cell transcriptomics read-out, and through this approach identify neuronal microexons that control autism-linked signatures underlying neuronal maturation and function

Wei et al. perform spatial transcriptomic profiling on synovial tissue biopsy samples from individuals with recent-onset rheumatoid arthritis, finding TGFβ signaling and fibrogenic fibroblast activation drive a treatment-refractory tissue phenotype.

Neville, Ferguson et al. show that non-canonical Polycomb repressive complex 1.1-mediated gene silencing is antagonized by DOT1L and is required for the therapeutic efficacy of Menin and DOT1L inhibitors in mixed-lineage leukaemia.

The transcription factor ATF4 and its effector lipocalin 2 (LCN2) have a key role in immune evasion and tumour progression, and targeting the ATF4–LCN2 axis might provide a way to treat several types of solid tumour by increasing anti-cancer immunity.

The deep learning model STARLING can generate accurate ensembles of intrinsically disordered regions of proteins using only protein sequence as input.

In this work, authors use whole genome tracking in a neonatal intensive care unit to reveal a strong link between Staphylococcus aureus colonization and invasive infection, pinpointing critical new targets for infection prevention in high-risk infants.

Chan and colleagues report that tumor ecosystem and microbiome features are associated with response to anti-PD-L1 avelumab plus chemoradiotherapy in patients with locally advanced head and neck cancer.

Alström syndrome (AöS) is a rare genetic disorder characterized by metabolic problems. Here, the authors show that in AöS models, defects in cilia and autophagy lead to ACBP accumulation, which drives obesity. An anti-ACBP antibody reduces weight gain and metabolic dysfunction, highlighting ACBP as a therapeutic target for this ciliopathy.

Native state proteomics of PV interneurons revealed unique molecular features of high translational and metabolic activity, and enrichment of Alzheimer’s risk genes. Early amyloid pathology exerted unique effects on mitochondria, mTOR signaling and neurotransmission in PV neurons.

Genetic models for psychiatric disorders often overlook ancestry diversity. Here, the authors use PsychENCODE and GWAS data to build ancestry-specific GReX models, improving TWAS and revealing novel genes and pathways linked to brain development and psychiatric risk.

How the complex interplay between multiple nutrients within the microenvironment dictates potential sites of metastatic cancer growth is explored.

Analysis of a placebo-controlled trial of a BCMA-targeting CAR-T cell therapy in patients with myasthenia gravis shows that CAR-T cell infusion selectively remodels the systemic immune environment, with elimination of BCMA-high plasma cells and activated plasmacytoid dendritic cells and changes in the autoreactive B cell repertoire.

McGrail and colleagues report that high intratumoral bacteria abundance is associated with an immunosuppressive microenvironment and resistance to immune checkpoint blockade in head and neck squamous cell carcinoma.

How white matter develops along the length of major tracts in humans remains unknown. Here, the authors identify fundamental patterns of human white matter development along distinct axes that reflect brain organization.

The impact of variants of uncertain significance (VUS) on protein function and cancer risk remain unclear. Here, the authors focus on the functional impact of VUS of the PALB2 gene and identify defects in DNA damage repair by homologous recombination associated with increased risk of breast cancer.

In one-shot perceptual learning, what we see can be dramatically altered by a single past experience. Using psychophysics, fMRI, iEEG, and DNNs, the authors identify neural and computational mechanisms underlying this remarkable ability in humans.

Evolutionarily related ‘proto-point’ centromeres providing resolution to the evolutionary origins of point centromeres are identified in yeast, and comparison shows they evolved in an ancestor with retrotransposon-rich centromeres and that long-terminal-repeat retrotransposons are the genetic substrate.

The therapeutic relevance of telomere maintenance mechanisms in cancer, remains to be explored. Here, the authors integrate multi-omic data and functional readouts, generate a resource of telomere biology metrics and identify potential molecular vulnerabilities.

Pertpy serves as a one-stop and performant framework for single-cell perturbation data analysis.

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.

People constantly decide whether to stop what they are doing to do something else. Here, the authors show that the quality of available options has a greater influence on people’s decisions to help others than to help themselves.

The 4D Nucleome Project demonstrates the use of genomic assays and computational methods to measure genome folding and then predict genomic structure from DNA sequence, facilitating the discovery of potential effects of genetic variants, including variants associated with disease, on genome structure and function.

Genetic variants of TREX1, a negative regulator of type I interferon responses, have been linked previously to non-monogenic systemic lupus erythematosus (SLE). Here the authors analyze UK Biobank multi-omics data to show that, while a derived oligoprotein interferon signature associates with increased SLE risk, TREX1 variants do not.