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When 100 social and behavioural science claims were examined, 34% of reanalyses closely matched the original results, with 74% reaching the same conclusion, revealing limited robustness of single-path analyses and the need to address analytical uncertainty.

Crohn’s disease is associated with disturbances in the B-cell compartment and secreted antibodies. Here, the authors reveal impaired colonic dimeric IgA responses in patients with Crohn’s disease and verify this phenotype in murine models, demonstrating that mitochondrial dysfunction drives defective mucosal humoral immunity.

An atlas highlights the heterogeneity of adipose tissue vasculature, identifies distinct endothelial subpopulations and provides insights into their contributions to metabolic disease.

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.

Glaciers lost 408 ± 132 Gt of mass during the hydrological year 2025, equivalent to 1.1 ± 0.4 mm sea-level rise. Since 1975, glacier mass loss has totalled 9,583 ± 1,211 Gt, equivalent to 26.4 ± 3.3 mm of sea-level rise, with six of the highest mass-loss years on record occurring in the past seven years.

How inflammation spreads from the skin to the joints in psoriatic disease is unclear. Here, the authors show that joint-resident fibroblasts can control differentiation of infiltrating skin-derived myeloid precursors that can become inflammatory macrophages.

An integrated high-resolution genetic, physical and shotgun sequence assembly of the barley genome, one of the earliest domesticated and most important crops, is described; it will provide a platform for genome-assisted research and future crop improvement.

Pathology-oriented multiplexing (PathoPlex) represents a framework for widespread access to multiplexed imaging and computational image analysis of clinical specimens at a relatively high throughput and subcellular resolution.

Hsp90s, molecular chaperones critically involved in many essential cellular processes, were the focus of a recent international conference held in Seeon, Germany. The scope of the conference ranged from structural and mechanistic insights all the way to medical applications.

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.

Familial adenomatous polyposis (FAP) is an inherited gastrointestinal syndrome associated with duodenal adenoma formation. Here the authors show that IL17A-producing NKp44- group 3 innate lymphoid cells accumulate in FAP duodenal tissue and are associated with duodenal adenoma formation in patients with FAP.

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.

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.

Within gastrointestinal tissues, tuft cells, a rare population of chemo-sensory epithelial cells, can promote the activation of type 2 innate lymphoid cells (ILC2s). Here the authors show that tuft cells and ILC2s are increased during gastric cancer development and that the pharmacologic inhibition of tuft cell derived IL25 or ILC2-produced IL13 reduces gastric tumor growth.

A pangenome of oat, assembled from 33 wild and domesticated oat lines, sheds light on the evolution and genetic diversity of this cereal crop and will aid genomics-assisted breeding to improve productivity and sustainability.

Studies on interferon-driven brain pathology have so far been hampered by the lack of appropriate animal models. Here the authors characterize RNASET2-deficient mice and show that neuroinflammation and brain atrophy are IFNAR1-dependent.

The activation and infiltration of immune cells to the vasculature is intimately linked to the immunopathology of hypertension. Here the authors implicate PI3Kγ signalling in the trafficking of CD8⁺ T cells between lymphoid and non-lymphoid organs, and the development of hypertension in a murine model.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

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

Oncogene induced senescence protects cells from unrestricted growth and cancer. Here, the authors show that PAK4 overrides this senescence in breast cancer cells through phosphorylation of RELB, thereby inhibiting transcription of the senescence regulator C/EBPβ.

Molecular analyses of longitudinal kidney biopsies from a phase 2 trial testing an anti-CD38 antibody for kidney transplant rejection show temporary suppression of antibody-mediated rejection during treatment, with molecular recurrence at 52 weeks.

Confident molecular identification is key for studying complex biochemistry. Here, the authors employ Quantum-Cascade Laser-based Mid-infrared imaging for rapid identification of ROIs, followed by MALDI imaging prm-PASEF for in-depth lipid identifications directly on complex tissues.

Deep Visual Proteomics combines machine learning, automated image analysis and single-cell proteomics.

White phosphorus (P₄) is very reactive but is relatively difficult to activate without relying on transition metals. Now, it has been shown that the degradation of P₄ can be mediated by two divalent silicon atoms in a bis(silylene) scaffold to give a diphosphorus complex that can be further functionalized and also act as a P⁻ transfer agent.

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.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

Mitochondria modulate both normal and premature aging, yet if primary oxidative phosphorylation deficiency can cause progeria has been unclear. Here, the authors show that mice with severe isolated respiratory complex III deficiency display cellular senescence and juvenile-onset segmental progeria.

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.

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

In glioblastoma (GBM), tumour microtubes (TM) connect tumour cells to a broader cellular network, with roles in tumour progression and therapy resistance. Here, the authors combine a dye uptake method in GBM xenograft models with subsequent scRNA-seq to infer a TM connectivity signature, finding CHI3L1 as a marker of connectivity.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

Intuitive control of bionic arms has greatly improved over the past years, however, it is still not possible to restore natural sensory feedback. Here, the authors create a biological communication interface for both controlling a prosthesis and supplying sensations associated with the missing limb in rats.

Fibroblast heterogeneity is a recognized feature in chronic kidney disease, and although fibrosis is integrant to the pathology, it is lesser known which of the fibroblast populations contribute. Here authors describe a population of proinflammatory fibroblasts, which are found in close proximity to macrophages and may facilitate their recruitment and acquisition of a FOLR2+, pathogenic phenotype.

EPO treatment improves cognition, but underlying mechanisms were unknown. Here the authors describe a regulatory loop in which brain networks challenged by cognitive tasks drift into functional hypoxia that drives—via neuronal EPO synthesis—neurodifferentiation and dendritic spine formation.

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.

The mechanisms governing the ontogeny and maturation of the mucosal immune system during the postnatal period are not well understood. Here the authors characterize the homing kinetic, anatomical distribution and maturation of early intestinal CD4 T cells and provide insights into active T-cell suppression during the postnatal period.

Hongu et al. find that perivascular macrophages stimulate activation of the pro-metastatic vascular niche via tenascin C stimulation of TLR4 and show that combined TLR4 and VEGF inhibition prevents TNC-mediated metastatic vascular activity.

The nuclear factor kappa B subunit c-Rel acts as a master regulator of metabolism and signalling in epithelial cells and macrophages that drives inflammation and fibrogenesis in various models of fibrosis.