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Despite high morbidity and mortality, there are currently no approved vaccines for protection against Middle East respiratory syndrome (MERS) coronavirus. Here the authors develop a ferritin nanoparticle-based MERS-CoV vaccine that elicits high levels of neutralizing antibodies in mice, non-human primates, and alpacas and prevents infection in an alpaca challenge model.

Antigen presentation in skull bone marrow by hematopoietic stem and progenitor cells induces myelopoiesis and generates CD4⁺ regulatory T cells in a mouse model of ependymoma, promoting immune tolerance. Treatment with anti-GM-CSF antibody has antitumor effects that are augmented by immunotherapy.

Mutations in the PBAF chromatin-remodeling complex cause various neurodevelopmental disorders. This study shows that PBAF shapes distinct motor neuron identities, revealing how its disruption impairs movement and offering insight into neurodevelopmental disorders caused by PBAF mutations.

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.

In the phase 1/2 TRIDENT-1 trial, treatment of patients with NTRK fusion–positive advanced solid tumors with the tyrosine kinase inhibitor repotrectinib—selective for ROS1, TRKA−C and ALK—was safe and resulted in durable systemic and intracranial clinical response.

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

Transcriptomic and clinical data analyses from multiple cohorts of patients with cancer receiving immunotherapy find that PD-1 blockade potentiates tumor-specific IgG1 plasma cell responses that complement cellular immunity and contribute to clinical benefit.

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.

De novo and inherited dominant variants in genes encoding U4 and U6 small nuclear RNAs are identified in individuals with retinitis pigmentosa. The variants cluster at nucleotide positions distinct from those implicated in neurodevelopmental disorders.

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.

Walmsley and colleagues report that systemic hypoxia induces persistent loss of histone H3K4me3 marks and epigenetic reprogramming in neutrophil progenitors, resulting in long-term impairment of subsequent neutrophil effector functions.

This Resource paper presents a global SARS-CoV-2 phylogenetic tree of 4,471,579 high-quality genomes consistently constructed by Viridian, an efficient amplicon-aware assembler.

Li and colleagues present CellScope, a tree-structured framework that reveals multi-level cellular hierarchies and gene functions in single-cell data. This approach provides clear clustering, intuitive visualization, and deep biological views into cell types and functions.

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.

This scenario study investigates how the EU net-zero target can be reached with varying levels of residual fossil fuels. Reducing fossils by only 90% relies on substantial carbon storage, while a full fossil phase-out requires a rapid scale-up of expensive carbon-neutral e-fuels.

Epstein–Barr virus (EBV) is a widespread herpesvirus linked to cancer and autoimmune disease. The authors in this work design and characterize a stabilized prefusion form of gB, an essential viral fusion protein, advancing EBV vaccine and therapeutic development.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

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.

K11/K48 branched ubiquitin chains regulate protein degradation and cell cycle progression. Here, the authors report the structural basis of how such a branched ubiquitin chain is recognized by the human 26S proteasome, revealing a multivalent binding mode that underlies selective recognition.

ADP-heptose binds to ALPK1, triggering transcriptional reprogramming and NF-κB activation, endowing pre-leukaemic cells with a competitive advantage due to excessive clonal proliferation.

Myeloid and lymphoid cells are derived from the same multipotent progenitor cell. Camargo and colleagues show that the transcription factor Mef2c restricts myeloid differentiation to favor production of B, T and natural killer cells.

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.

Re-exposure to a high-fat diet in mice led to emergency myelopoiesis and increased neutrophils in the blood, which infiltrated plaques and released neutrophil extracellular traps, exacerbating atherosclerosis.

An understanding of the molecular mechanisms promoting the generation of immunoregulatory and tumour-promoting monocytes and macrophages is key to breaking the cycle of tumour myelopoiesis and developing more effective myeloid-targeting therapies.

Ying, Paulson and collagues have developed an open-source framework, Biolearn, to harmonize and systematically evaluate 39 aging biomarkers across diverse populations, enabling standardized validation and facilitating development of robust aging biomarkers.

Here, the authors find that relative abundances of stress-sensitive gastrointestinal microbes at age 2 years predicts internalizing symptoms in middle childhood through altered emotion-related brain network connectivity.

Inbreeding depression has been observed in many different species, but in humans a systematic analysis has been difficult so far. Here, analysing more than 1.3 million individuals, the authors show that a genomic inbreeding coefficient (FROH) is associated with disadvantageous outcomes in 32 out of 100 traits tested.

Vyas and colleagues show that a continuum of hemopoietic progenitor cells from human cord blood execute lymphoid and myeloid differentiation.

This study shows that cancer stem cell in breast tumours have lower levels of reactive oxygen species (ROS) than the rest of the tumour cells. This property renders cancer stem cells less sensitive to radiation therapy, which may cause radioresistance in breast cancer.

Progranulin deficiency causes untreatable neurodegenerative diseases. Here, the authors show that hematopoietic stem cell transplantation and optimized brain conditioning correct the disease phenotype in progranulin-deficient mice.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

Using multi-ancestry genome-wide association study and fine-mapping, 298 loci and 36 credible genes are identified in the aetiology of bipolar disorder.

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.

Aged hematopoietic stem cells (HSC) are characterised by reduced regenerative potential and a loss of quiescence. Here, the authors show nicotinamide riboside treatment shrinks the age-enlarged stem cell pool and shifts aged HSC functionally, metabolically and molecularly towards the young state.

Here the authors provide an explanation for 95% of examined predicted loss of function variants found in disease-associated haploinsufficient genes in the Genome Aggregation Database (gnomAD), underscoring the power of the presented analysis to minimize false assignments of disease risk.

Dick and colleagues identify human LT-HSC subsets with distinct quiescent states. They link these differences to INKA1-mediated downregulation of the transmembrane protein CD112 and its interaction with the protein deacetylase SIRT1. INKA1 is inversely correlated with the histone H4K16Ac mark, which then distinguishes ‘latent’ CD112^lo LT-HSCs from CD112^hi LT-HSCs that are more readily activated in response to hematopoietic stress.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

Here, the authors report recent updates to the ENCODE data portal including a redesigned home page, an improved search interface, custom-designed pages highlighting biologically related datasets and an enhanced cart interface for data visualisation plus user-friendly data download options.

Hematopoietic stem cells are generated during development, though how and when they become dormant long term-HSCs remains unclear. Here they show that retinoic acid receptor levels are regulated by a IκBα-PRC2 axis in HSCs, and that IκBα KO mice have HSCs that are fewer in number, but functionally and molecularly more dormant.

The cell adhesion molecule E-selectin regulates haematopoietic stem cell self-renewal in the bone marrow vascular niche. Here, the authors show E-selectin adhesion directly induces survival signaling in acute myeloid leukaemia and therapeutic inhibition improves chemotherapy outcomes in mice.

Smoke PM_2.5 could result in 71,420 excess deaths per year in the USA by 2050 under the SSP3-7.0 high-warming scenario.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

Anti-disialoganglioside (GD2) antibody therapy has proven beneficial to neuroblastoma patients and intra-tumoral copper levels have been associated with immune evasion. Here the authors show that copper chelation potentiates anti-GD2 immunotherapy through improved infiltration and function of Fc receptor bearing neutrophils.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.