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This study introduces single-cell transcription factor (TF) sequencing, a single-cell barcoded and doxycycline-inducible TF overexpression approach that reveals dose-sensitive functional classes of TFs and cellular heterogeneity by mapping TF dose-dependent transcriptomic changes during the reprogramming of mouse embryonic multipotent stromal cells.

Here the authors construct an artificial pathogen cell with tunable rigidity and find crosstalk between these and macrophages. Macrophages probe the artificial pathogen surface, and increasing rigidity of the artificial pathogen promotes proinflammatory polarization of macrophages.

This work presents scEpi²-seq, a method for simultaneous single-cell profiling of DNA methylation and histone modifications, enabling direct investigation of the interplay between these two epigenomic marks.

Current photoproximity labelling methods often require metal-based catalysts to map protein interactomes but, owing to their toxicity, they have limited intracellular applicability. A deazaflavin cofactor has now been developed as a biocompatible alternative for diazirine activation inside living cells, offering accurate mapping of protein interactors and dynamics with excellent spatio-temporal control.

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.

In this work, authors show that deletion of FprB enhances the antibacterial activity of gallium against Pseudomonas aeruginosa, revealing a combination strategy and demonstrating the utility of CRISPRi-seq for therapeutic target discovery.

Managing power exhaust in fusion reactors is a key challenge, especially in compact designs for cost-effective commercial energy. This study shows how alternative divertor configurations improve exhaust control, enhance stability, absorb transients and enable independent plasma regulation.

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.

NV center-based quantum sensors integrated into diamond anvil cells have enabled magnetic imaging under high pressure but are less suited for studying magnetic van der Waals materials. Here, the authors demonstrate magnetic imaging of micrometer-sized flakes of 1T-CrTe2 under high pressure using spin-centers in a thin hBN layer.

Al-Hilal, Chrysovergi et al. identify a role for durotaxis in lung fibrosis and metastatic pancreatic cancer, mediated by the FAK–paxillin mechanosensor complex, and demonstrate therapeutic targeting of this pathway using the small molecule JP-153.

Isotope engineering can enhance spin coherence of solid-state defects, such as NV centers in diamond but progress for defects in hBN has been limited. Gong et al. report the optimization of isotopes in hBN and demonstrate improved coherence and relaxation times for the negatively charged boron vacancy centers.

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.

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.

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.

In this multicenter phase 1 trial, treatment with IBI343, a CLDN18.2-targeting antibody–drug conjugate, was safe and showed encouraging clinical responses in patients with advanced gastric or gastroesophageal junction adenocarcinoma.

In condensed matter physics, p-wave chiral superfluidity is an unconventional topological many-body quantum state. Here, Liu et al. report a new mechanism to achieve a centre-of-mass p-wave chiral superfluid state in a spin imbalanced atomic Fermi gas with s-wave interaction.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

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.

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.

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.

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.

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.

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.

The LHCb experiment at CERN has observed significant asymmetries between the decay rates of the beauty baryon and its CP-conjugated antibaryon, thus demonstrating CP violation in baryon decays.

To better understand the etiology of frailty, the authors perform a large genetic study. They identified 45 additional variants and implicated MET, CHST9, ILRUN, APOE, CGREF1 and PPP6C as potential causal genes, linking frailty to immune regulation, metabolism and cellular signaling.

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.

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.

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.

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.

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.

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.

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.

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.

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.

In this work, authors show that the nucleoside prodrug obeldesivir has potent antiviral activity across respiratory syncytial virus (RSV) clinical isolates with a high resistance barrier. Once-daily obeldesivir treatment was efficacious against RSV in a non-human primate model.

An oceanic plate joint, where two sets of plate fabrics intersect, may have led to weakening, tearing and a window opening in the slab subducting beneath the Alaska Peninsula, according to ambient noise seismic tomography.

Using ethnically and geographically diverse metagenomic data, the authors identify microbiota alterations associated with inflammatory bowel disease (IBD). They discover universal IBD-associated bacteria, which serve as the basis for a multibacteria biomarker panel that could support a noninvasive tool for IBD diagnosis.

Self-intercalated Chromium tellurides consist of CrTe₂ van der Waals layers, with additional Chromium atoms residing in the van der Waals gap. This highly tuneable class of magnetic materials has presented a range of unique magnetic phenomena, and here Bigi, Jego, Polewczyk et al add to this by showing that CrTe₂ (δ = 0.25 − 0.50) hosts orthogonal ferromagnetism.

This study used fine-mapping to analyze genetic regions associated with bipolar disorder, identifying specific risk genes and providing new insights into the biology of the condition that may guide future research and treatment approaches.

As presented at the 2025 ASCO Annual Meeting: in a randomized platform phase II trial, high rates of pathologic complete response were seen for neoadjuvant durvalumab plus chemotherapy when combined with new agents, most notably a TROP2-targeting antibody–drug conjugate, in patients with resectable non-small-cell lung cancer.

Arrays of ultracold gas atoms trapped in an optical lattice can mimic many of the behaviours of conventional matter and give rise to exotic quantum states of matter as well. Li et al. suggest that a system of atoms in a two-legged ladder-like lattice could exhibit topological insulator and topological superconductor states.

Deletion of upstream tumor suppressors of the Hippo/YAP pathway is frequent in papillary renal cell carcinoma (pRCC). Here, the authors employ a transgenic mouse model, single-cell transcriptomics and public genomic datasets to show that targeting hyperactivated YAP1 prevents neoplastic renal epithelial cell immune evasion and impairs the development of pRCC.