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Regulation of gene expression is a facet of human brain specialization. Here, the authors show that human-like expression of the CLOCK gene in the mouse neocortex enhances cognitive flexibility and neural connectivity, suggesting an evolutionary gain of function that may have contributed to human cognitive specialization.

Here the authors reveal a study of 486,956 Han Chinese individuals showing that most people with genetic variants affecting drug response do not have the predicted adverse events, highlighting the challenges of implementing pharmacogenetics in clinical practice.

This study demonstrated that different types of HC-Pros from potyviruses exhibit varying capacities to inhibit HEN1. This results in distinct levels of autophagic AGO1 degradation, which in turn leads to differences in RNA silencing suppression efficiency.

The presence of long non-coding RNAs (lncRNAs) is pervasive across genomes, yet few lncRNAs have clearly established mechanisms of action. Here the authors demonstrate that the fission yeast lncRNA nc-tgp1 regulates expression of the drug tolerance gene tgp1₊ via⁺transcriptional interference.

Advances in beta cell differentiation have propelled cell therapies for diabetes into the clinic; this Review outlines the lessons learned from early-phase trials and discusses the clinical, manufacturing and regulatory challenges that must now be overcome.

In this phase 3 trial, first-line treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma with anti-PD-1 finotonlimab plus cisplatin plus 5-fluorouracil (C5F) prolonged overall survival compared with placebo plus C5F.

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.

The in vitro characterization of a key event in the early stages of meiosis—the induction of double-strand DNA breaks by the SPO11–TOP6BL complex—provides insight into the catalytic mechanism and evolution of SPO11.

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.

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.

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.

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.

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.

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.

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.

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.

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.

A recombinant vaccine that targets the receptor-binding domain of the spike protein of SARS-CoV-2 induces a potent antibody response in immunized mice, rabbits and non-human primates, and protects primates from infection with the virus.

A pangenome analysis of 76 wild and domesticated barley accessions in combination with short-read sequence data of 1,315 barley genotypes indicates that allelic diversity at structurally complex loci may have helped crop plants to adapt to agricultural ecosystems.

Cardiac I/R injury is a deleterious issue in the clinic. Here, the authors show that Tisp40 facilitates HBP flux and protein O-GlcNAcylation through binding to the promoter of GFPT1, thereby preventing cardiac I/R injury.

The adaptor protein zyxin is known for its mechanosensing function in the maintenance of actin network. Here the authors show that zyxin is key to blood homeostasis and thrombosis by controlling the endothelial release of von Willebrand factor and the formation of actin scaffolds on exocytic granules.

Two-dimensional magnets with intrinsic ferromagnetic/antiferromagnetic ordering are highly desirable for future spintronic devices. Here, the authors demonstrate a chemical vapor deposition approach to controllably grow ultrathin FeTe crystals with antiferromagnetic tetragonal and ferromagnetic hexagonal phase, showing a thickness-dependent magnetic transition.

Whole-slide images (WSI) and digital pathology are valuable approaches for the analysis of tumours and their microenvironments. Here, the authors present scMTOP, a framework to characterise tumour ecosystems and intercellular relationships at the single-cell level from WSIs, which they apply to breast cancer samples.

In the multicenter, phase 3 DAWNA-1 trial, the combination of dalpiciclib, a new cyclin-dependent kinase 4 and 6 inhibitor, with fulvestrant, in patients with HR⁺HER2⁻ advanced breast cancer who progressed or relapsed on endocrine therapy, improved progression-free survival with manageable safety and may represent a new treatment option.

Devices with a wide-temperature range persistent photoconductivity (PPC) and low power consumption is a challenge for optical synaptic devices in neuromorphic computing. Here, the authors develop a carbon nanotube/porphyrin heterojunction on a flexible array, achieving PPC between 77 K to 400 K.

To avoid head fixation or drawbacks of miniaturized devices for freely moving rodents, a robotic device can move a headstage for microscopy or electrophysiology with the animal, thereby enabling naturalistic behavior.

Artificial organelles can potentially be used support cellular functions, but there is a trade-off between cellular uptake and cellular retention. Here, the authors report the dynamic assembly of DNA-ceria-based artificial peroxisomes in cells, and show they can be used to reduce intracellular ROS.

LKB1 is frequently mutated in lung squamous cell carcinomas. Here, the authors show that sole LKB1 depletion is sufficient to drive the development of this cancer, where downstream defective MKK7-JNK1/2 signalling activates the ∆Np63/p63 pathway to induce subsequent epithelial cells transformation and tumour progression.

Fuel cells are promising for converting fuel into electricity, but rely on development of high-performance catalysts for oxygen reduction. Here the authors report a highly durable platinum-trimer decorated cobalt-palladium catalyst with low platinum loading for electrocatalysis of oxygen reduction.

The genome of the scallop Patinopecten yessoensis is sequenced. This bivalve mollusc has a slow-evolving genome with features such as karyotype and Hox gene expression that may be close to that of the ancestral bilaterian.

Analysis of whole-genome sequencing data across 2,658 tumors spanning 38 cancer types shows that chromothripsis is pervasive, with a frequency of more than 50% in several cancer types, contributing to oncogene amplification, gene inactivation and cancer genome evolution.

Analysis of mitochondrial genomes (mtDNA) by using whole-genome sequencing data from 2,658 cancer samples across 38 cancer types identifies hypermutated mtDNA cases, frequent somatic nuclear transfer of mtDNA and high variability of mtDNA copy number in many cancers.

Efficient, large-scale genomic analysis is facilitated on the cloud by a computational tool with error-diagnosing and self-healing capabilities.