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Lazarevic et al. reveal a shared loss of a TBX5-dependent atrial gene network in cardiomyocytes and a disease-specific network gain in activated fibroblasts across atrial fibrillation and heart failure models.

The application of polygenic risk scores to individual-level disease susceptibility is challenging, as risk is evaluated at a group-level. Here, the authors describe a machine learning method, Mondrian Cross-Conformal Prediction, that reports disease status conditional probability value at the individual level.

An algorithm that combines deep learning, Bayesian optimization and computer vision techniques can be used to autonomously tune a semiconductor spin qubit from a grounded device to Rabi oscillations.

David Altshuler and colleagues explore the genetic architecture of type 2 diabetes (T2D) using an integrated population genetics–based simulation framework calibrated with empirical data. Whereas they are able to exclude more extreme models, for example, those in which either common or rare variants explain all of the disease heritability, they find that a broad range of architecture remains consistent with current empirical data and suggest that continued large-scale sequencing and genotyping studies will be needed to more precisely characterize the genetic architecture of complex traits such as T2D.

Global Burden of Disease estimates show that between 1990 and 2023, the prevalence and burden of drug use disorders, inclusive of amphetamine, cannabis, cocaine and opioid use, have been increasing in high-income countries, particularly in the USA.

Here, as part of the Sherlock-Lung study, the authors profile the microbiomes of 940 lung cancers in never smokers finding no significant associations with demographic and clinical features, suggesting lung bacteria are unlikely to have a sizable role in lung cancer.

The wastewater sector is a major source of non-CO₂ emissions, but accurate emissions accounting remains challenging, despite guidelines for basic inventories provided by the IPCC. This research reveals that national inventories widely omit key sources and apply inconsistent methods, which lead to greatly under-reported emissions.

The present study shows that maternal presence beyond early life remains crucial for brain, behavioural and physiological development in young horses, highlighting the importance of the mother–offspring relationship during a childhood-like stage.

An in-depth analysis of tissue biopsies from patients with multiple myeloma and CAR T cell therapy-associated immune-related adverse events (CirAEs) after treatment with commercial BCMA-targeted CAR T cell therapy shows that CD4⁺ CAR T cells mediate off-tumor toxicities and that high CD4:CD8 ratio at apheresis, robust early CAR T cell expansion, ICANS and ciltacabtagene autoleuce treatment are independently associated with the development of CirAEs.

In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

De novo domestication was performed on the brassica Thlaspi arvense (pennycress) by identifying and stacking CRISPR-induced mutations to create a new intermediate oilseed crop that can be grown in the off-season, with seed compositions similar to canola (low erucic acid and reduced glucosinolate).

The authors present DNA-Diffusion, a generative AI framework that designs synthetic regulatory elements with tunable cell-type specificity. Experimental validation demonstrates their ability to reactivate AXIN2 expression, a leukemia-protective gene, in its native genomic context.

Pilcher et al. present a single-cell transcriptomics-based immune atlas of participants with newly diagnosed multiple myeloma, reporting on the association of cell types, gene expression and intercellular interactions with disease progression phenotypes.

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.

Zhang, Lahry, Cipurko et al. show that the microbial metabolites queuine and preQ₁ modify the same host tRNA. PreQ₁-tRNA reduces cell proliferation, slows tumour growth, decreases the translation of ribosomal proteins and is cleaved by IRE1 on the ER ribosome.

Type 2 inflammation drives the formation of pathologic mucus in patients with asthma. Here, authors reveal a role for intelectin-1 in IL-13-induced mucus properties, and that an ITLN1 eQTL is associated with protection from the formation of mucus plugs in T2-high asthma.

Water-vapor interfaces have been studied with many techniques, yet open questions persist about their electronic and molecular structure. Here, the authors demonstrate the application of soft x-ray second harmonic generation to study the water surface by leveraging attosecond pulses at the LCLS and a flat liquid sheet microjet, providing insights on the H-bond structure.

This study finds that crowd-sensed plants as living sensors uncover climate and soil patterns in 326 European cities; extend the urban heat island effect to moisture, pH, salinity and disturbance; and show built-up areas homogenize whereas urban forests preserve environmental diversity.

Using the single-cell Deep Visual Proteomics technique, the authors develop a resource providing spatially resolved proteomic analysis of individual cells in human liver tissue.

cfDNA fragmentomics is a potential clinically applicable method for identifying cancer. Here, the authors assess fragmentomics analysis methods and their application to commercial targeted sequencing panels.

Here, the authors report an exome-wide association study for multi-organ imaging traits by leveraging recent bioinformatic tools such as AlphaMissense. The identified signals elucidate the genetic effects from rare variants on human organs and their connections to complex diseases

FAME is a biobank-scale method that tests whether the effect of an SNP on a quantitative trait is modulated by an individual’s polygenic background. FAME can also be used to estimate of the proportion of variance explained by such marginal epistasis effects

Exercise has considerable health benefit, including modulation of the immune system. Here the authors compare the molecular make-up of peripheral blood immune cells at resting state and upon a single bout of two different aerobic exercise modes by proteomics and show that although both exercise modes trigger similar changes, the effect is more pronounced after high intensity interval training.

The reconstitution of complex biological processes in cell-free systems can support the detailed characterisation of biochemical mechanisms which are difficult to probe in vivo. Here authors present an all-cell-free T7 phage cycle, consisting of cell-sized liposomes encapsulating a cell-free gene expression reaction and a phage receptor at the membrane.

Researchers analyzed 5,279 plasma proteins in 40 people undergoing feminizing gender-affirming hormone therapy over 6 months, revealing significant changes in 299 proteins. Such changes could have implications for reproductive capacity, immune regulation and long-term health.

Current single-cell RNA sequencing methods struggle to comprehensively profile transcriptomes, with many lowly expressed transcripts remaining undetected. Here authors present a workflow for enhancing the detection of both transcripts and regions of interest in combination with a standard transcriptome profile.

An analysis of data from the Sherlock-Lung study provides insight into the mutational processes that contribute to lung cancer in never smokers, and looks at the possible role of factors such as air pollution and passive smoking.

Absorption in one-port passive systems is known to be bound by causality constraints. Here, authors study reflection and transmission of a two-port system to introduce a generalized causality constraint based on duality symmetry. Experimentally, the broadened bandwidth of their meta-absorbers shows the untapped absorption potential of broadband acoustic metamaterials.

While the emergence of immune checkpoint inhibitors has improved outcomes in patients with small cell lung cancer (SCLC), tumour that develop means of immune evasion become resistant. Here, the authors report that ERBB2 signalling induces loss of MHC Class I expression and subsequently immune evasion in preclinical models of SCLC.

Vaccine-derived poliovirus type 2 currently spreads similarly to historical poliovirus—unidirectionally across neighbouring countries at a median velocity of 2.3 km per day. International borders are associated with slower velocity when immunity is high.

Madrer et al. identify a Parkinson’s disease–specific increase in transfer RNA (tRNA) fragments in human blood, cerebrospinal fluid and postmortem brain tissue, demonstrating the ability of blood-based tRNA fragment quantification to distinguish between pre-symptomatic patients and healthy controls.

Modelling of the evolution of atmospheric methane emissions from the 2022 Nord Stream subsea pipeline leaks shows that the event emitted the largest recorded amount of methane from a single transient event.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

Qu, Razmara et al. show that Gli1+ fetal cells give rise to long-lived cartilage progenitors in the long bones. While normally dormant until postnatally, they expand upon (and compensate for) growth perturbations, arising from external Pdgfra+ cells.

Tissue phenotypes arise from molecular states of individual cells and their spatial organisation, so spatial omics assays can help reveal how they emerge. Here, the authors apply graph neural networks to classify tissue phenotypes from spatial omics patterns, and use this approach to understand patterns in cancers and their microenvironments.

How much methane will be emitted from the boreal-Arctic region under climate change is not well constrained. Here the authors show that accounting for distinct wetland and lake classes leads to lower estimates of current methane loss as some classes emit low amounts of methane.

Understanding principles that govern protein association with extracellular vesicles should expand their potential as a therapeutic modality. Here, the authors show that by localizing proteins to the plasma membrane and lipid rafts, a variety of proteins can be preferentially loaded into extracellular vesicles.

Paul and colleagues report the development and characterization of an antibody–drug conjugate targeting TRBC2 for the treatment of T cell malignancies.

Demand for agricultural water resources under climate change may come into conflict with achieving positive environmental outcomes. In Australia’s Macquarie basin, environmentally minded management can ensure agricultural needs are met without sacrificing environmental outcomes.

Donor spin impurities in silicon are promising qubit candidates, but efficient control and coupling of distant spins remains a key challenge. In this work, the authors experimentally demonstrate coherent coupling between a superconducting flux qubit and individual bismuth donor spins in silicon.

An error detecting code running on a trapped-ion quantum computer protects expressive circuits of eight logical qubits with a high-fidelity and partially fault-tolerant implementation of a universal gate set.

On-chip spectrometers typically have limited spectral channels and low signal to noise ratios. Here the authors introduce a digital architecture that uses switches to change the interferometer path lengths, enabling exponentially more spectral channels per circuit element and lower noise by leveraging a machine learning reconstruction algorithm.

The IPCC uses probabilistic statements to describe uncertainty in the projections of models. Now a multinational study, across 17 languages, shows that people interpret IPCC statements as implying probabilities closer to 50% than intended by the IPCC authors. If numerical ranges are included, interpretations better reflect the IPCC guidelines.

Prediction of protein structures on the scale of genomes remains a challenge. Here the authors introduce a protein structure prediction method that uses deep learning to predict inter-atomic distances, torsion angles and hydrogen bonds, and apply it to predict the structures of 1475 Pfam domains.

Post-infectious myalgic encephalomyelitis/chronic fatigue syndrome (PI-ME/CFS) is a disabling disorder, yet the clinical phenotype is poorly defined and the pathophysiology unknown. Here, the authors conduct deep phenotyping of a cohort of PI-ME/CFS patients.