Search

The anterior cingulate cortex encodes affective pain behaviours modulated by opioids; targeting opioid-sensitive neurons through a new chemogenetic gene therapy replicates the analgesic effects of morphine, providing precise chronic pain relief without affecting sensory detection.

CDK4/6 inhibitors are promising treatments for ER+ breast cancer, however resistance remains a challenge. Here, the authors analyse the NeoPalANA cohort and indicate that a 33 gene signature was predictive of response to neoadjuvant anastrozole and palbociclib.

Researchers studied the blood-based metabolome of over 23,000 people from ten ethnically diverse cohorts. They identified 235 metabolites associated with future risk of type 2 diabetes (T2D). By integrating genetic and modifiable lifestyle factors, their findings provide insights into T2D mechanisms and could improve risk prediction and inform precision prevention.

Reduced fitness of the tumor microenvironment is mediated by a long non-coding RNA expressed in tumors.

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 role of vascular plasticity in brain function remains poorly understood. Here, the authors demonstrate that a significant portion of blood vessels in the adult brain periodically occlude and regress, a process that is associated with a reduction in neuronal activity.

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.

Complete sequences of chromosomes telomere-to-telomere from chimpanzee, bonobo, gorilla, Bornean orangutan, Sumatran orangutan and siamang provide a comprehensive and valuable resource for future evolutionary comparisons.

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.

Castleman disease encompasses a group of disorders characterised by abnormal lymph node morphology. Here the authors use single cell and spatial transcriptomics to assess the stromal, immune and interaction architecture of different subtypes of Castleman disease, indicating potential ligand-receptor interactions between immune cells.

Despite their discovery in the 19th century, the islands of Calleja, clusters of densely packed granule cells in the ventral striatum, remain enigmatic. This study reveals that islands of Calleja neurons are critical for grooming control in mice.

Two impact-melt fragments in Chang’e-6 lunar soils reveal that the Apollo basin was formed at ~4.16 Ga, implying a non-cataclysmic late heavy bombardment on the Moon between 3.8 and 4.0 Ga.

Accurate real-time tracking of dexterous hand movements and interactions has applications in human–computer interaction, the metaverse, robotics and tele-health. Capturing realistic hand movements is challenging due to the large number of articulations and degrees of freedom. Tashakori and colleagues report accurate and dynamic tracking of articulated hand and finger movements using machine-learning powered stretchable, washable smart gloves.

Comprehensive integration of gene expression with epigenetic features is needed to understand the transition of kidney cells from health to injury. Here, the authors integrate dual single nucleus RNA expression and chromatin accessibility, DNA methylation, and histone modifications to decipher the chromatin landscape of the kidney in reference and adaptive injury cell states, identifying a transcription factor network of ELF3, KLF6, and KLF10 which regulates adaptive repair and maladaptive failed repair.

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 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.

Multi-ancestry genome-wide association analyses identify 124 risk loci for rheumatoid arthritis, of which 34 are novel. A polygenic risk score based on multi-ancestry data showed comparable performance between populations of European and East Asian ancestries.

Interferon-γ (IFNγ)-activated calcium/calmodulin-dependent protein kinase II (CAMK2) phosphorylates phosphoserine aminotransferase 1 (PSAT1) at serine 337 (S337), enabling glutathione peroxidase 4 (GPX4) interaction, promoting α-ketoglutarate-dependent PHD3-mediated GPX4 proline 159 (P159) hydroxylation and stabilizing GPX4 to counteract ferroptosis.

The core circadian transcription factor BMAL1 regulates circadian-dependent myocardial injury.

GABA_Breceptors drive presynaptic excitation in habenula cholinergic neurons to regulate the extinction of fear memories in mice.

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.

Proliferative vitreoretinopathy (PVR) is a vision-threatening response to ocular injury, in which retinal cells secrete tractional, scar-forming proteins. Here, the authors show that antibody blockade of either Annexin A2 or its inducer, macrophage inflammatory protein-1, prevents PVR in mice.

A rabies virus-based monosynaptic tracing method is used to show that the external globus pallidus plays a critical role in cocaine-induced behavioural plasticity.

Multi-omic time course experiments reveal intricate biology of salt stress response mechanisms of the historically and industrially relevant algae, Scenedesmus obliquus UTEX393.

Using data from a single time point, passenger-approximated clonal expansion rate (PACER) estimates the fitness of common driver mutations that lead to clonal haematopoiesis and identifies TCL1A activation as a mediator of clonal expansion.

Entamoeba histolytica, the causative agent of fatal diarrhoeal disease in children in the developing world, is shown here to kill human cells by biting off and ingesting pieces of cells, in a process reminiscent of the trogocytosis seen between immune cells; ingestion of bites is required for killing and this mechanism is used both in tissue culture and during invasion of intestinal explants.

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.

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.

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.

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 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.

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.

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.

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.

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.

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.

Together with a companion paper, the generation of a transcriptomic atlas for the mouse lemur and analyses of example cell types establish this animal as a molecularly tractable primate model organism.

Together with an accompanying paper presenting a transcriptomic atlas of the mouse lemur, interrogation of the atlas provides a rich body of data to support the use of the organism as a model for primate biology and health.

The molecular and cellular causes of glaucoma are not well understood. Here, the authors integrate GWAS with genetic regulation and single cell expression from multiple eye tissues to identify genes and key cell types that affect glaucoma pathogenesis.

Multi-modal analysis is used to generate a 3D atlas of the upper limb area of the mouse primary motor cortex, providing a framework for future studies of motor control circuitry.