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Greenwald, Nederlof and colleagues developed a computational pipeline analyzing multiplex imaging data and established spatial patterns within breast cancer microenvironment that are predictive of immune checkpoint blockade response across treatment time course.

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.

Methods used to date a network of marine sediment cores reveal that rapid retreat of the Ross Ice Shelf was contemporaneous with the lowering of nearby outlet glaciers, implicating warm ocean waters as a driver of Antarctic deglaciation.

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.

The authors analyzed the whole-exome sequences of over 16,000 individuals and found that very rare variants predicted to disrupt the SETD1A gene confer substantial risk for schizophrenia. Damaging variants in SETD1A were also associated with diverse, severe developmental disorders, providing an important genetic link between schizophrenia and other neurodevelopmental disorders.

HER2-targeted therapy improves patient’s outcome in early breast cancer. Here, the authors present the efficacy and biomarker analysis of two HER2-targeted combinations (ado-trastuzumab emtansine plus pertuzumab and paclitaxel, trastuzumab and pertuzumab) in the context of the neoadjuvant I-SPY2 phase 2 adaptive platform trial for early breast cancer at high risk of recurrence.

NIPBL perturbation activates long terminal repeat (LTR)-derived alternative promoters due to reorganization of chromatin’s hierarchical structure, leading to LTR co-option and oncogene activation in melanoma cell lines.

Durable and robust lymph-node expansion is associated with the efficacy of therapeutic vaccination, as shown in mice immunized via a biomaterial-based vaccine.

A focused-ultrasound-mediated mechanogenetics approach enables the genetic modification of cancer cells near solid tumours to activate chimeric antigen receptor T cell response and achieve tumour suppression at distinct sites.

Hematopoietic stem cells (HSCs) differentiate into multiple lineages, with such capacity impacted by aging. Here the authors identify Kit^lo HSCs as a functionally distinct population that exhibits distinct lymphoid-primed chromatin landscapes, which drive enhanced lymphoid reconstitution capacity, and is altered in aged hosts.

Food biodiversity is likely to benefit both human health and agrifood systems. To assess food biodiversity, this epidemiological study proposes the use of dietary species richness, which is highly heterogeneous—both between and within countries—and is associated with lower rates of mortality in Europe and similar levels of micronutrient adequacy in low- and middle-income countries, as opposed to other classical indices.

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.

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).

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.

In an updated report on 70 laboratory-confirmed highly pathogenic avian influenza A H5N1 cases in the USA between March 2024 and May 2025, the absence of human-to-human transmission to date was confirmed, with no known mutations of resistance to neuroaminidase inhibitors.

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

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.

In this Stage 2 Registered Report, Buchanan et al. show evidence confirming the phenomenon of semantic priming across speakers of 19 diverse languages.

The fungal pathogen Candida auris can acquire amphotericin B resistance through clinically rare mutations in sterol biosynthesis genes but at a certain fitness cost, which reduces its infection potential. Compensatory evolution can, however, mitigate this cost.

A retrospective analysis using PCR testing, viral enrichment-based sequencing and agnostic metagenomic sequencing finds an association between adeno-associated virus type 2 and paediatric hepatitis of unknown cause.

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.

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.

A high-bandwidth neuromotor interface offers performant out-of-the-box generalization across people.

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.

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.

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.

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.

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.

The characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet-base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.

Genome-wide analyses identify variants associated with infertility and reproductive hormone levels but find limited polygenic overlap between reproductive hormone levels and infertility at the population level.

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.

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

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.

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.

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.

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.

We evaluated the use of chimeric antigen receptor-modified T cells targeting GD2 (GD2-CART) for H3K27M⁺ diffuse midline glioma (DMG), finding that intravenous administration of GD2-CART, followed by intracranial infusions, induced tumour regressions and neurological improvements in patients with H3K27M-mutant pontine or spinal DMG.

Oral rotavirus vaccine (ORV) efficacy varies between countries, but underlying reasons aren’t fully understood. In this prospective cohort study, authors show that maternal rotavirus-specific antibodies in serum and breastmilk and pre-vaccination microbiota diversity are negatively correlated with ORV response in India and Malawi but not in the UK.

In the I-SPY2.2 trial, patients with high-risk stage 2/3 breast cancer received neoadjuvant datopotamab–deruxtecan plus durvalumab, followed by sequential chemotherapy with or without targeted therapy, with the option of early surgical resection after each block of therapy, showing that de-escalation of therapy is possible for several patient subgroups without compromising outcome and avoiding toxicity of standard chemotherapy.

Based on phylogenomic and geometric morphometric analyses of 132 anglerfish species, the authors infer a Cretaceous origin of the clade and show that bathypelagic anglerfish are undergoing rapid phenotypic diversification despite inhabiting a relatively homogeneous deep-sea habitat.

Two doses of the coronavirus disease 2019 vaccine ChAdOx1 nCoV-19 boost antibody responses and functions in phase 1/2 trial participants.

Despite new treatment options, prognosis for patients with glioblastoma (GBM) remains poor. Here the authors report the clinical course of patients with GBM treated with a personalized neoantigen-derived peptide vaccine treated within the scope of an individual healing attempt.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

Altered mechanotransduction has been proposed as a mechanism for disease pathophysiology, yet evidence remains scarce. Here, the authors show that antibodies from patients with bleeding disorders bind to integrins and modulate platelet cell contraction force, and this correlates with clinical symptoms.