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Determining how replication forks move across the human genome is critical for the effective use of agents that target replication stress. Here, the authors present DNAscent, an AI supported assay for DNA replication stress in human cells using Nanopore sequencing data.

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.

Estimates of chikungunya virus prevalence across 180 countries and territories show that Southeast Asia, Africa and the Americas carry the most substantiative burden, which would require reactive vaccine campaigns against new outbreaks and routine immunization in heavily endemic areas to reduce transmission.

Decisions are typically associated with a sense of confidence and can be followed by an impulse to change our minds. Here, the authors use intracranial recordings in humans to show that confidence and changes of mind derive from a cortical process called evidence accumulation.

Cell migration in confined environments is initiated by a cytoplasmic pool of anillin and Ect2 that promotes RhoA/myosin II-mediated activation at the poles of migrating cells, in a process dependent on the extracellular environment stiffness.

Cross-species transcriptomics on vulnerable neuronal populations unravels the transcription factor CREB3 and its regulatory network as resilience markers of ALS. Genetics and epidemiology further identify the protective rare variant CREB3R119G.

Natural scenes contain statistics that are constrained in both space and time. Here, the authors show that, in insects as in mammals, both higher order neural mechanisms and behavioural discrimination are tuned to natural spatial statistics.

Through RNA profiling of right ventricular tissue from patients with chronic thromboembolic pulmonary hypertension, Jafari et al. uncover mechanisms underlying disease severity-associated remodeling, identify key signaling molecules involved in fibrotic and proliferative pathways, and reveal processes driving right ventricular recovery after pulmonary endarterectomy.

Colorectal cancer metastasis involves dramatic plasticity and loss of PROX1-mediated repression of non-intestinal lineages.

CRISPR-Cas13 RNA-targeting systems comprise an invaluable set of tools in the fields of basic and applied sciences. Here, Moreno-Sánchez, Hernández-Huertas, and Nahón-Cano et al. enhanced the use of the CRISPR-RfxCas13d system in zebrafish for targeted depletion of endogenous mRNAs.

A long- and short-read barley pan-transcriptome assembled from 20 diverse barley genotypes offers insights into genotype- and tissue-dependent gene expression and function.

A large, open dataset containing parallel recordings from six visual cortical and two thalamic areas of the mouse brain is presented, from which the relative timing of activity in response to visual stimuli and behaviour is used to construct a hierarchy scheme that corresponds to anatomical connectivity data.

A red blood cell haemostatic mechanism induced by dying ECs functions independently of platelets and fibrin.

New high-resolution datasets for the Amazon forest show a loss of carbon in 2010-2020, with gains by forest growth outweighed by losses by deforestation and degradation. Human losses intensified over time, reinforcing the need for stronger policies.

Improved imaging methods are crucial to map pancreatic ductal adenocarcinoma (PDAC). Here, the authors analyse PDAC samples using spatial transcriptomics and proteomics, identify claudin-4 as a potential theranostic target, and develop an imaging agent to track claudin-4 in primary and metastatic PDAC tumours.

Stereotactic needle biopsies are currently performed for diagnosis only in glioblastoma; this study highlights the depth of information available through multi-omics analysis.

Human cortical maturation is organized along the sensorimotor-association axis. Here, the authors investigate in multiple cohorts if the development of functional connectivity during adolescence conforms to this hierarchy.

Engineering stabilized proteins is essential for industrial and pharmaceutical biotechnologies. Here, authors present Stability Oracle, a Graph-Transformer framework trained on protein masked microenvironments to predict protein thermodynamic stability, using less training data while achieving improved generalization.

Matthews et al. present a protein sequence embedding based on data from ancestral sequences that allows machine learning to be used for tasks where training data are scarce or expensive.

A preinfusion circulatory inflammation biomarker-based signature predicts the likelihood of treatment failure in patients with non-Hodgkin lymphoma who were treated with CAR-T cell therapy, with an inflammatory cluster assignment being prognostic of clinical response and survival outcomes.

Pressure overload in the heart, such as from aortic stenosis, triggers early molecular changes before visible damage occurs. Here, the authors show that combining proteomics, transcriptomics, and genetic data reveals key drivers of heart failure, highlighting potential targets for treatment.

Independent statistical reconstructions of the global mean surface temperature from either ocean or land data show that existing estimates of early-twentieth-century ocean surface temperatures are too cold.

Transcriptional regulators (TRs) play critical roles in both normal tissue development and disease progression. Here, the authors introduce a Bayesian hierarchical model capable of identifying key TRs from epigenomics-based query region sets with enhanced accuracy and interpretability.

Analysis of large-scale CRISPR screening data, combined with experiments in patient-derived tumour organoid models, identifies PELO as a potential therapeutic target in chromosomal 9p21.3-deleted cancers and microsatellite-unstable cancers harbouring specific mutations.

Genetic diversity between clinical and environmental fungal isolates of Aspergillus flavus is poorly studied. Here, the authors analysed genomic data from a global set of clinical and environmental A. flavus isolates and report that clinical prevalence is associated with population structure.

By developing a method for single-embryo multi-omics in Drosophila, the authors provide a high-resolution view into the transcriptional and metabolic underpinnings of early embryonic development.

The prognostic and diagnostic roles of DNA methylation in acute myeloid leukemia remains to be explored. Here, the authors develop DNA methylation-based models for the prediction of five-year survival and clinical molecular subtypes in both pediatric and adult test cohorts.

The emergence of resistant subpopulations often underlies the development of resistance to cancer therapy. Here, using a DNA barcoding approach, the authors demonstrate EGFR TKI treatment in non-small cell lung cancer enriches for resistant subpopulation which can be prevented by treatment with the multikinase inhibitor sorafenib via inhibition of MKNK, STAT3 and MCL1.

G49, a dual glucagon/glucagon-like peptide-1 receptor agonist, triggers an inter-organ crosstalk between adipose tissue, pancreas and liver, leading to brown fat activation with the final outcomes of increased energy expenditure and body weight loss.

Voloudakis and colleagues find statistically significant but weak associations between professional categories and genetic predisposition for neuropsychiatric traits.

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.

Here the authors report single-cell and spatial transcriptomics of young and aged male fibrotic mouse lungs. Age-related alterations in capillary sub-populations are associated with a proangiogenic phenotype linked to regeneration of the alveolar niche.

The largest harmonized proteomic dataset of plasma, serum and cerebrospinal fluid samples across major neurodegenerative diseases reveals both disease-specific and transdiagnostic proteomic signatures, including a robust plasma profile associated with the APOEε4 genotype.

In a post-hoc analysis of circulating tumor DNA (ctDNA) features from patients with metastatic prostate cancer treated with [¹⁷⁷Lu]Lu–PSMA-617 or cabazitaxel in the randomized phase 2 TheraP trial, low ctDNA levels at baseline were predictive of clinical benefit from [¹⁷⁷Lu]Lu–PSMA-617, and PTEN or ATM alterations were identified as potential biomarkers of response.

GIANT, a genetically informed brain atlas, integrates genetic heritability with neuroanatomy. It shows strong neuroanatomical validity and surpasses traditional atlases in discovery power for brain imaging genomics.

Carbonic anhydrase (CA) mimics have promising applications in the enhanced hydration and sequestration of CO₂, but limited success has so far been achieved. Here, the authors report the assembly of sequence-defined peptoids into crystalline nanomaterials with controlled microenvironment of active sites as CA mimics for promoted hydration and sequestration of CO₂.

Translating genotype to phenotype is a grand challenge in biology. Here, the authors investigate the utility of genome, transcriptome, and methylome data and their combinations in predicting six plant complex traits and uncovering key genes and genetic interactions in Arabidopsis.

This study employs a functional genomic approach to identify a synthetic lethal interaction between CDS1 and CDS2 in uveal melanoma and other cancers, which may represent a potential therapeutic target.

In Alzheimer’s disease (AD), disruptions in myelin and axonal structures occur, although the underlying mechanisms remain unclear. Here the authors show that, at the myelin–axon interface, axon–glial signaling, paranodal architecture and amyloid-β aggregation are altered in AD, implicating myelin–axon disruption in disease progression.

Chung et al. show that total-body dynamic positron emission tomography can allow non-invasive quantitative imaging of the molecular permeability of the human blood-brain barrier using various molecular radiotracers.

Excitatory pyramidal neurons preferentially target inhibitory interneurons with the same selectivity and, in turn, inhibitory interneurons preferentially target pyramidal neurons with opposite selectivity, forming an opponent inhibition motif that supports decision-making.

With increasing river flow, sand dunes on the riverbed initially grow and eventually flatten out. However, flume experiments show that dune height distributions under high flow are bimodal, suggesting flickering between high and low dune heights.

In two independent studies, Song et al. and Jiang, Dalgarno et al. present computational frameworks, perturbation-response score and Mixscale, respectively, to determine individual cellular variation in response to perturbation.