Search

This study reveals how distal DNA ‘switches’ control gene activity in human astrocytes. Using CRISPRi screens and single-cell RNA-seq, we map enhancer–gene links, highlight Alzheimer’s disease-related targets and introduce a model that predicts additional regulatory interactions.

Gray et al. find that the genetic overlap between alcohol use disorder and body mass index consists of variants with mixed directions of effect and implicates brain regions involved in executive functioning, reward and food intake regulation.

Antibody–bottlebrush conjugates expand the options for drug cargos compared to antibody–drug conjugates.

The authors develop and characterise a selective Greatwall inhibitor, C-604, and show that its cytotoxicity stems from PP2A-B55α hyperactivation. They identify B55α and Greatwall levels as biomarkers of responses to Greatwall-targeted therapy.

Ycf1, a C-family member ATP Binding Cassette (ABC) transporter, transports glutathione and glutathione-metal complexes in yeast. Here the authors use cryo-EM and biochemical analysis to show how an intrinsically-disordered regulatory domain (R-domain) controls activity upon phosphorylation by engaging with a Nucleotide Binding Domain.

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.

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 this work, authors utilise comparative transcriptomics to reveal lncRNAs that distinguish pathogen-specific from core macrophage responses. They identify a Q fever-specific AHR-regulated CYP1B1-AS1/CYP1B1 axis that modulates mitochondrial homeostasis and survival of Coxiella burnetii.

Native ion mobility mass spectrometry reveals two isoforms of the two-pore domain K⁺ channel K2P4.1 have distinct binding preferences for lipids and show a relationship between the strength of individual lipid binding events and channel activity.

Cas9 DNA targeting is inherently sequence specific but not temporally controlled. Here, authors spatiotemporally couple Cas9 activity to target site transcription in eukaryotes and exploit this to preferentially edit the more highly transcribed of two alleles that harbor identical Cas9 targets.

Sleep loss has been known to increase seizure risk since antiquity, but the underlying mechanisms remain unclear. Using fruit-fly epilepsy models, the authors show that rising “sleep drive”, not sleep duration, is what triggers seizures.

Accurate protein synthesis depends on aminoacylated tRNAs, but their identities have been hard to measure. Here, authors present aa-tRNA-seq, a nanopore-based method that reveals the amino acid, sequence, and modification status of individual tRNAs at single-molecule resolution.

Observations of a fast X-ray transient reveal that it is a gamma-ray-burst explosion from a very distant galaxy that emits light with the wavelength necessary to drive cosmic reionization, the last major phase change in the history of the Universe.

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.

Sharks and rays are vital coral reef species. This study shows that nearly two thirds (59%) of the 134 coral-reef associated species are threatened with extinction. The main cause of their decline is found to be overfishing, both targeted and unintentional, and extinction risk is greater for larger species found in nations with higher fishing pressure and weaker governance.

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.

Here, the authors study the impact of doxycycline pre-exposure prophylaxis (doxyPrEP) on the microbiome of men who have sex with men on HIV PrEP, showing that doxyPrEP use results in minimal compositional changes in the microbiome over 12 months.

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.

Here, the authors show that IRX3 is a transcriptional master regulator of multiple histone- and chromatin-remodeling enzymes and the SUMOylation pathway in adipocyte precursor cells. IRX3 ablation results in a SUMOylation-dependent switch from adipogenic to osteogenic identity.

The Progressive Supranuclear Palsy Rating Scale (PSPRS) was modified to improve clinical meaningfulness and sensitivity. Fifteen items were selected, and rescored PSPRS was more practical and sensitive to disease progression over 12 months.

Eye2Gene’s next-generation phenotyping of multimodal images increases diagnostic yield for inherited retinal diseases by improving screening, phenotype-driven variant prioritization and automatic similarity matching in phenotypic space to drive gene discovery.

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.

The discovery of 2023 KQ₁₄, a Sedna-like object with a perihelion of 66 au, fills a gap in the known population. Its orbit does not align with other Sedna-like objects, shedding light on the diversity and dynamical history of the outer Solar System.

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.

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

The SPECULOOS project detected an Earth-sized planet in a short orbit around a nearby Jupiter-sized star. This planet, SPECULOOS-3 b, is one of the most promising rocky exoplanets for detailed emission spectroscopy characterization with JWST.

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.

Pan-cistrome of the maize leaf under well-watered and drought conditions profiled by haplotype-specific MOA-seq highlights the relevance of transcription factor binding QTLs for understanding phenotypic diversity in maize.

Far-red kinase biosensors are applied to image kinase signaling networks at super resolution.

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 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.

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.

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.

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.

A strategy for inferring phase for rare variant pairs is applied to exome sequencing data for 125,748 individuals from the Genome Aggregation Database (gnomAD). This resource will aid interpretation of rare co-occurring variants in the context of recessive disease.

Dietary protein influences metabolic health and ageing. Here Solon-Biet et al. show that, rather than having a direct toxic effect, dietary branched-chain amino acids (BCAAs) appear to induce hyperphagia, owing to an imbalance between BCAAs and other amino acids, which reduces lifespan as a consequence of obesity.

Solar photovoltaics is entering a multi-terawatt era, driven by decades of cost, performance and reliability gains. In this Perspective Alberi et al. discuss the role of historical and future learning, highlighting the increasing importance of sustainability considerations.

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.

A multinational randomized trial shows that task-sharing via nonspecialist providers and the use of telemedicine platforms, delivery models that can overcome barriers to scalability and access, are noninferior to specialists and in-person models for treating perinatal depression.

Deep-sea hydrothermal plumes support an array of microbial metabolisms, but the fate of organic carbon in these systems is unknown. Here, the authors used metabolic rate assays and metagenomic data to show that heterotrophic bacteria contribute significantly to carbon cycling in the deep sea.

Here, the authors show how in β-thalassemia, a perturbed bone marrow microenvironment leads to altered hematopoiesis. Reduced TGFβ reduces autophagy levels, in turn reducing dormancy and priming of haematopoietic stem cells and multipotent progenitors towards erythroid lineage.

This study shows that many plants form a second, deeper root layer underground, enabling access to nutrient-rich deep soil. This previously unnoticed rooting pattern adds to the growing recognition that deep soil dynamics are overlooked.

A case–control study investigating the causes of recent cases of acute hepatitis of unknown aetiology in 32 children identifies an association between adeno-associated virus infection and host genetics in disease susceptibility.