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Soil microbes drive ecosystem functions but are vulnerable to environmental stressors triggered by global change. This study reveals that multiple environmental stressors drive community-level restructuring of soil functional microbiomes globally.

Protein synthesis is tightly regulated by the integrated stress response, but therapeutic activation remains challenging. Here, the authors identify a drug‑like allosteric inhibitor, an ISRAC, that stabilises inactive eIF2B, mimicking stress‑induced eIF2α phosphorylation to activate the ISR, establishing eIF2B as a tractable target for ISR modulation.

Augustine et al. present a multimodal graph neural network that identifies cancer immunotherapy targets. It distinguishes approved and prospective targets, and promising candidates are validated using a clinically relevant patient-derived platform.

Different approaches to achieving Target 3 affect distinct and socially diverse populations. These contrasting socioeconomic contexts imply varying challenges and opportunities, underscoring the importance of context-specific, equitable implementation.

High-resolution in situ cryo-electron tomography in Schizosaccharomyces pombe identifies SNOR protein, which binds to ribosomes during dormancy induced by glucose depletion, priming them for rapid reactivation of protein synthesis upon glucose repletion.

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 national classification system of wetland hydrologic connectivity to streams, which could be applied globally, demonstrates and advances current understanding of how wetland connectivity affects surface water quality.

This study explores the clonal architecture of aplastic anemia across age using single-cell approaches. Somatic inactivation of specific human leukocyte antigen risk alleles is a frequent event and often occurs in multiple independent events.

Snyder et al. analyze two population-based birth cohorts to test associations of newborn metabolite concentrations and childhood respiratory outcomes. C4, C10:1, C18:2, and citrulline are associated with early-life wheezing and asthma, with C18:2 specifically associated with increased non-allergic asthma risk.

The JWST thermal emission spectrum of the rocky exoplanet LHS 3844 b points to a dark, basalt-like surface shaped by space weathering. The data provide tight limits on CO₂ and SO₂, ruling out a substantial atmosphere and recent widespread volcanism.

RNA velocity is a widely used method to predict the fate of single cells. Here the authors show that the concept can be adapted to predict the fate of individual human subjects, using RNA velocity of whole blood at a single point in time to predict future clinical outcomes and treatment responses.

Nicotinamide adenine dinucleotide (NAD) biosynthetic enzymes have been reported to be oncogenic. Here, the authors show that NAPRT, a key enzyme in the deamidated NAD biosynthesis pathway, functions as a suppressor of colon inflammation and tumorigenesis by maintaining DNA repair capability.

The mode of action of eukaryotic initiation factor 5A (eIF5A), a translation factor activated by hypusination, remains to be characterized. Here, the authors suggest that hypusinated eIF5A is involved in mitochondrial metabolism and translation promoting prostate cancer progression.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

Curiosity detected over 20 organic molecules in 3.5-billion-year-old Martian rocks using a wet chemistry experiment, showing complex carbon compounds can survive for billions of years and may preserve clues about Mars’ past habitability

Using nasal brush biopsies from the olfactory region, single-cell profiling revealed neuroimmune alterations in Alzheimer’s Disease detectable at a pre-clinical stage, offering an accessible window into early neurodegenerative disease in humans.

Analyses of snRNA genes in a French cohort of people with rare disorders, with validation through international collaboration, identify monoallelic and biallelic variants in RNU2-2 as frequent causes of neurodevelopmental disorders with epilepsy.

A deep learning model using smartwatch data was shown to predict peak oxygen uptake and unplanned healthcare events in the TRUE-HF prospective cohort of patients with heart failure, as well as unplanned healthcare utilization in patients with heart failure in the All of Us Research Program.

Androgen activity in the male embryonic hindbrain prolongs hindbrain differentiation in male individuals and drives sex differences in the incidence and prognosis of posterior fossa type A (PFA) ependymoma, an aggressive childhood brain tumour.

As presented at the 2026 AACR Annual Meeting: in a phase 1b trial, patients with microsatellite-stable colorectal cancer received a FAP-4-1BB ligand together with the CEA-directed T cell engager cibisatamab; the treatment was safe, and biomarker analysis showed induction of immunity in line with the biological rationale.

RNA editing influences gene regulation in cancer. Here, the authors show that EZH2 regulates RNA editing by ADAR1 through remodeling its interactome and nuclear transport, thereby promoting MDM2 expression and prostate cancer progression.

The authors resolve 63 structurally diverse haplotype structures for the 22q11.2 deletion syndrome region. Deletion risk differs depending on structure; individuals of African ancestry are enriched for inverted repeats that predispose to inversion.

Here, Wulczynski et al. find fewer small-intestinal fiber-degrading bacteria in CeD patients, independent of the gluten-free diet, while inulin-supplemented diet in gluten-sensitized mice facilitates microbial saccharolytic function and SCFAs, accelerating mucosal healing in the small intestine.

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.

BRCA1 and BRCA2 are well known breast cancer predisposition genes, however, many variants have not yet been classified for their pathogenicity. Here, the authors analyse a large combined cohort to provide evidence of variant pathogenicity.

Authors implemented a strategy integrating genomic and healthcare exposure data to track nosocomial transmission in real-time and evaluated it on a regional outbreak in Michigan. Passively collected isolates may inform interventions to stop spread.

Baum et al. present a synthesis of field data, remote-sensed data, media reports and process-based modelling analyses examining the effects of the 2021 heatwave in western North America for 32 terrestrial and marine taxa as well as gross primary productivity, streamflow and wildfire activity.

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.

Hutchinson-Gilford Progeria Syndrome is characterized by premature aging with cardiovascular disease being the main cause of death. Here the authors show that inhibition of the NAT10 enzyme enhances cardiac function and fitness, and reduces age-related phenotypes in a mouse model of premature aging.

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

cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

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.

T cells integrate signals from self-ligands not only during thymic development but also as they circulate through secondary lymphoid organs. These encounters with self in the periphery shape their activation and function, thereby ‘training’ T cells to interpret and respond to foreign antigens.

Glucocorticoid receptor activation is a key driver of resistance of triple-negative breast cancer to both CD8⁺ T cells and natural killer cells during initial metastatic seeding.

Breast cancer risk for BRCA1/BRCA2 mutation carriers varies depending on other genetic factors. Here, the authors perform a case-only genome-wide association study and highlight novel loci associated with breast cancer risk for BRCA1/BRCA2 mutation carriers.

In atopic dermatitis (AD), skin barrier disruption leads to chronic inflammation. Here, the authors use single-cell sequencing to map human skin, uncovering AD-specific cell states and populations involved in immune responses and cell differentiation.

In an integrated analysis of transcriptomic data from the SUBSPACE consortium and public datasets of patients with sepsis, acute respiratory distress syndrome, trauma and burns, dysregulation within four consensus molecular clusters related to myeloid and lymphoid cells is associated with mortality and illness severity.