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A CRISPR screen reveals that loss of structural components of the SAGA complex derails hematopoiesis by decoupling epigenetic control. This halts stem cell maturation, triggers a pathogenic interferon program and boosts human MDS-L cell growth.

MedHELM, an extensible evaluation framework including a new taxonomy for classifying medical tasks and a benchmark of many datasets across these categories, enables the evaluation of large language models on real-world clinical tasks.

Engineered mucus-tethering bispecific nanobodies neutralize and entrap viruses to enhance mucosal immunity, preventing influenza infection and limiting SARS-CoV-2 transmission.

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.

Newly developed mouse models that enable cell-specific analyses of proteostasis dynamics across the lifespan of the mice reveal key aspects of neuronal proteostasis with ageing.

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

Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic.

Via an integrative modelling approach that combines population and clinical trial data, the authors find that polygenic risk score-based screening would reduce premature mortality across seven commonly screened conditions.

The ratio between the levels of two synaptic proteins in cerebrospinal fluid predicts future cognitive resilience versus decline among presymptomatic individuals and individuals with early Alzheimer’s disease harboring amyloid and tau pathology.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

The tolerogenic activity of type 1 conventional dendritic cells (cDC1s) is determined by EPOR, which is preferentially expressed in cDC1s and induces antigen-specific FOXP3-expressing regulatory T cells.

Estimates from the Global Burden of Disease study reveal declines in chronic respiratory disease mortality between 1990 and 2023—especially during the COVID-19 pandemic—but the burdens on people affected remain substantial.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

Crystal structures of HIV Env trimer with native glycosylation in complex with neutralizing antibodies reveal a glycan shield of high-mannose and complex-type N-glycan and indicate a path for germline-targeting vaccine design.

Vassy, Dornisch and colleagues developed a genomics-based prostate cancer risk model to support a randomized clinical trial of precision screening in a national healthcare system.

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.

Many premalignant colorectal polyps in familial adenomatous polyposis arise polyclonally rather than from a single mutated cell, showing diverse early evolutionary trajectories that frequently occur without clonal APC or KRAS driver events.

Large-effect variants in autism remain elusive. Here, the authors use long-read sequencing to assemble phased genomes for 189 individuals, identifying pathogenic variants in TBL1XR1, MECP2, and SYNGAP1, plus nine candidate structural variants missed by short-read methods.

Analysis combining multiple global tree databases reveals that whether a location is invaded by non-native tree species depends on anthropogenic factors, but the severity of the invasion depends on the native species diversity.

Floquet engineering is often limited by weak light–matter coupling and heating. Now it is shown that exciton-driven fields in monolayer semiconductors produce stronger, longer-lived Floquet effects and reveal hybridization linked to excitonic phases.

Cell type labelling in single-cell datasets remains a major bottleneck. Here, the authors present AnnDictionary, an open-source toolkit that enables atlas-scale analysis and provides the first benchmark of LLMs for de novo cell type annotation from marker genes, showing high accuracy at low cost.

The phase 2/3 DEVOTE trial demonstrated that high-dose nusinersen significantly improved motor function and was safe in patients with spinal muscular atrophy, compared with a matched sham control.

Ulcerative colitis (UC) is associated with epithelial metabolic derangements which exacerbate gut inflammation. Here the authors report that colonoids from children with ulcerative colitis exhibit hypermetabolism and cellular stress primarily driven by lipid dysregulation. Pharmacological inhibition of PPAR-a, a transcriptional regulator of lipid metabolism, alleviates epithelial stress and inflammation.

Application of multiancestry and ensemble-based approaches yields improved polygenic risk prediction models for breast cancer and its subtypes among women of African ancestry.

The existing ENCODE registry of candidate human and mouse cis-regulatory elements is expanded with the addition of new ENCODE data, integrating new functional data as well as new cell and tissue types.

Genetic and physical maps for the 16 chromosomes of Saccharomyces cerevisiae are presented. The genetic map is the result of 40 years of genetic analysis. The physical map was produced from the results of an international systematic sequencing effort. The data for the maps are accessible electronically from the Saccharomyces Genome Database (SGD: http://genome-www.stanford.edu/Saccharomyces/).

In a large-scale proteomic study of biological aging of 11 organs from 44,498 individuals in the UK Biobank, the biological ages of the brain and immune system emerged as strong predictors of healthspan and longevity.

Nature Biotechnology’s annual survey highlights academic start ups that are, among other things, correcting misfolded or disordered proteins, creating second-generation GPCR agonists, building a new gene delivery platform and mining cancer genomes for novel targets.

This paper uses a multi-region model to show that single-region models used by thousands of companies to estimate CO2 emissions related to goods they purchase may drastically underestimate and misidentify the largest sources of upstream emissions.

Myeloid-specific mechanotransduction ablation downregulates pro-fibrotic fibroblast transcriptional profiles to reduce scar formation in human cells

Chure et al. analyse experimental data to show that E. coli bacteria maintain stable protein density ratios between cytoplasm and membranes. In addition, they develop a biophysical model that predicts surface-to-volume ratio from ribosomal content and protein partitioning across cell compartments.

Together with a companion paper, the generation of a transcriptomic atlas for the mouse lemur and analyses of example cell types establish this animal as a molecularly tractable primate model organism.

Using data from a single time point, passenger-approximated clonal expansion rate (PACER) estimates the fitness of common driver mutations that lead to clonal haematopoiesis and identifies TCL1A activation as a mediator of clonal expansion.

Cost-effective, environmentally sustainable and energy-efficient ways to address rising atmospheric CO₂ levels are urgently needed. Here the authors combine electrochemical reduction of CO₂ to formate with biosynthetic conversion of formate to the universal building block acetyl-CoA using a synthetic metabolic pathway called ReForm.

The early genetic evolution of uveal melanoma (UM) remains poorly understood. Here, the authors perform genetic profiling of 1140 primary UMs, including 131 small early-stage tumours, finding that most genetic driver aberrations have occurred by the time small tumours are biopsied; in addition, the15-gene expression profile discriminant score can predict the transition from low- to high-risk tumours.

DNA methylation and gene expression data integration identify aging-related genes in blood that predict health outcomes, offering new insights into aging biology and potential therapeutic targets.

Affinity-proteomics platforms often yield poorly correlated measurements. Here, the authors show that protein-altering variants drive a portion of inter-platform inconsistency and that accounting for genetic variants can improve concordance of protein measures and phenotypic associations across ancestries.

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.

Georgiadis and colleagues conduct micron-resolution fibre mapping on multiple histological tissue sections. Their light-scattering technique works across different sample preparations and tissue types, including formalin-fixed paraffin-embedded brain sections.

Together with an accompanying paper presenting a transcriptomic atlas of the mouse lemur, interrogation of the atlas provides a rich body of data to support the use of the organism as a model for primate biology and health.

Blood plasma protein data was combined with machine learning models for a simple method to determine differences in organ-specific aging; the study provides a basis for the prediction of diseases and aging effects using plasma proteomics.

One of three back-to-back papers to show that dosage of BACH2 can modulate T cell differentiation and function and how we might apply this to enhance CAR T cell therapies for cancer.

Designing single molecules capable of complex sensing functions is challenging. Now, using crowdsourced RNA designs from the online game Eterna, compact single-molecule sensors have been demonstrated for a variety of tasks, including a complex three-input tuberculosis diagnostic. The development of a Monte Carlo Tree Search algorithm enabled automated design of similarly sophisticated nucleic-acid sensors.

SPACEc offers a user-friendly, expert-curated workflow for multiplexed image analysis, enabling researchers to easily perform advanced spatial biology studies and streamline the path from experiment to discovery.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

CRISPR-Cas9-based screens have allowed the study of gene-drug interactions. Here, the authors develop CRISPR-Cas9 knock-out, activation and repression screens in human gastric 3D organoids, also integrating single-cell CRISPR screens, to identify genes involved in the response to cisplatin in gastric cancer.

Trends in global H₂ sources and sinks are analysed from 1990 to 2020, and a comprehensive budget for the decade 2010–2020 is presented.