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Precise and efficient CRISPR genome editing requires specialized delivery systems. Here, the authors develop Coomassie lipidoids that deliver purified adenine base editors into retinal tissues, making it possible to achieve robust genome editing with a defined, non-viral nanomedicine.

Anti-phased changes in Antarctic Circumpolar Current strength between the Indian and Pacific sectors of the Southern Ocean occurred on orbital timescales over the past one million years, linked to glacial cycles and obliquity forcing, according to proxy records and modelling.

Variation in responses to bacterial and viral stimuli between Batwa rainforest hunter-gatherers and Bakiga agriculturalists from Uganda suggests population-level divergence under natural selection, with hunter-gatherers disproportionately showing signatures of positive selection.

The role of normally silenced transposable elements (TEs) in tumorigenesis remains unclear. Here, the authors show that increased expression of TEs in both patients and mice with colitis or by DNA hypomethylating drugs elicits a viral mimicry response that suppresses tumorigenesis. This viral mimicry response inhibits the stemness of cancer initiating cells in a cell autonomous manner.

Mapping of the neutrophil compartment using single-cell transcriptional data from multiple physiological and patological states reveals its organizational architecture and how cell state dynamics and trajectories vary during health, inflammation and cancer.

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.

There is a lack of effective therapies for patients with non-V600E BRAF mutant cancer. Here, the authors report limited response in a phase II trial investigating the combination of binimetinib (MEK inhibitor) and encorafenib (BRAF inhibitor) for the treatment of non-V600E BRAF mutant cancer and subsequently investigate resistance mechanisms and combination therapeutic strategies in patient-derived models.

Glaciers in New Zealand retreated at about the same time as mid-latitude glaciers in the Northern Hemisphere during Heinrich Stadials, indicating strong global teleconnections during the last glacial period, according to a marine sediment record.

Wastewater-based surveillance tends to focus on specific pathogens. Here, the authors mapped the wastewater virome from 62 cities worldwide to identify over 2,500 viruses, revealing city-specific virome fingerprints and showing that wastewater metagenomics enables early detection of emerging viruses.

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.

As presented at the ESMO Congress 2025: Results of the phase 2/3 AGITG DYNAMIC-III trial show that de-escalated chemotherapy based on ctDNA-negative status in patients with stage III colon cancer did not meet non-inferiority for 3-year recurrence-free survival when compared to standard of care, although it enables better informed treatment decisions.

Dietary restriction promotes the expansion of effector T cells via ketone bodies, which enhances anti-tumour immunity and synergizes with immunotherapy in mice.

The INTIMET study is a randomized 26-week double-blind clinical trial to assess whether metformin can reduce insulin resistance in adults with type 1 diabetes. Metformin did not reduce insulin resistance in type 1 diabetes, but lowered insulin dose versus placebo – a secondary outcome.

Age-related macular degeneration (AMD) is a common cause of vision loss with a large genetic risk in older individuals. Here, for a high-risk AMD subtype, the authors identify an association with a chromosome 10 risk region containing a long non-coding RNA.

Uneven toxin production in giant centipedes due to morphological and physiological constraints has been evolutionarily exapted through neuromuscular innervation and neurotransmitter stimulation to provide behavioural control over venom composition.

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.

Federated learning (FL) algorithms have emerged as a promising solution to train models for healthcare imaging across institutions while preserving privacy. Here, the authors describe the Federated Tumor Segmentation (FeTS) challenge for the decentralised benchmarking of FL algorithms and evaluation of Healthcare AI algorithm generalizability in real-world cancer imaging datasets.

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.

Neurodegenerative disorders remain poorly treated despite their growing disease burden. Here, authors developed a multiplexed screening platform that identified DNAJB6 as a modulator of condensate maturation and suppressor ALS/FTD-linked toxicity.

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.

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

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.

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.

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.

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.

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 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.

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.

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.

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.

Autoimmune encephalitis (AIE) may involve neuron-specific cytotoxic T cells, but evidence is still lacking. Here the authors use induced pluripotent stem cells from patients with AIE and single cell RNA-sequencing of ex vivo CD8 T cells to find neuron-specific, KIR⁺CD8⁺ T cells with altered transcriptome that potentially contribute to AIE etiology.

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.

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.

Magnetotelluric data provide evidence of a large melt-rich magmatic reservoir beneath Mayotte island that might be connected to the system that fed the large submarine eruption of Fani Maoré in 2018–2019.

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.

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.

Strontium isotope analysis can be applied to animal and plant tissues to help determine their provenance. Here, the authors generate a strontium isoscape of sub-Saharan Africa using data from 2266 environmental samples and demonstrate its efficacy by tracing the African roots of individuals from historic slavery contexts.

The safety and efficacy of ribonucleoproteins for genome editing can be enhanced by formulations of lipid nanoparticles optimized for enhanced stability, delivery efficiency and editing potency of the protein complexes.

Direct visualization of chiral effects in topological chiral semimetals remains elusive. Here, Sessi et al. demonstrate that quasiparticle scattering at impurities in the two enantiomers of PdGa gives rise to handedness dependent quantum interference patterns.