Search

Global Burden of Disease analysis found that in 2023, suboptimal diet was estimated to be responsible for 4 million deaths and 97 million morbidity burdens from ischemic heart disease.

Drug development is slowed down by manual formulation and testing. Here, the authors present an integrated digital formulator and self-driving tableting system that rapidly designs and manufactures tablets, thereby reducing material consumption and development time.

The authors have applied an eight-tissue rat multi-omic dataset to analyze the gene regulatory landscape of endurance exercise training, identifying tissue-specific regulatory patterns involved in muscle function, metabolism and immune response.

This study utilized a longitudinal cohort of adolescents to identify distinct brain signatures linked to ADHD symptom trajectories, revealing that specific cortical and subcortical changes correlate with symptom persistence, remission and emergence, enhancing predictive capabilities for ADHD outcomes.

The herpes simplex virus lytic-latent balance is incompletely understood. In this study, the authors show that it is controlled by the relative abundance of host activating and repressive forkhead box (FOX) transcription factors that recruit epigenetic cofactors to the viral genome to remodel viral chromatin.

Calcium sparks are the elementary detectable units of calcium release through ryanodine receptors (RyRs). Hou et al. correlate Ca²⁺ sparks with RyR cluster configurations and provide insights into the dynamics of Ca²⁺ release in live cardiomyocytes at baseline and in pathological conditions.

The global burden of Metabolic syndrome is incompletely characterized. Here the authors report a systematic review and modelling study showing that global metabolic syndrome prevalence doubled from 2000 to 2023, now affecting 1.54 billion adults (31.0% of women, 25.7% of men), with higher rates in women, urban areas, and high-income countries, with disparities across regions.

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 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 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.

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.

Severe congenital development defects such as Jeune syndrome can result from the malfunction of primary cilia and dynein. Here Schmidts et al. report unique biallelic null mutations in a gene encoding a dynein light chain, helping to explain the nature of ciliopathies in human patients.

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.

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.

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.

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.

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.

Chromosomal rearrangements may hamper intraspecific hybrid fertility. Here the authors show that environment-specific genetic incompatibility segregates readily within intermating populations and leads to intrinsic reproductive isolation within a yeast species.

The use of oncolytic viruses as a therapy for cancer is limited by mechanisms inhibiting viral replication in the tumor. Here, the authors show that a chemical derivative of itaconate, 4-octyl itaconate, increases oncolytic virus VSVΔ51 efficacy in various cancer models, through decreasing antiviral immunity.

A high-bandwidth neuromotor interface offers performant out-of-the-box generalization across people.

Inactivating PPP2R1A mutations correlate with better survival after immune checkpoint blockade in patients with ovarian clear cell carcinoma, suggesting that targeting the phosphatase 2A (PP2A) pathway may represent an effective startegy for improving responses to immunotherapy.

mRNA vaccines have been successfully developed, but a better understanding of in vivo distribution of the encoded antigen may aid further improvements. Here the authors use PET imaging and demonstrate transient expression of the vaccine antigen in the injection site and draining lymph nodes in mice and non-human primates.

A new RNA reference set improves detection of differential expression in clinical settings.

Here, the authors produce an updated termite classification with genomic scale analyses, highlighting thirteen family-level lineages and resilience of their classification to future termite research.

Genome-wide RNA sequencing/PAR-CLIP and short interfering RNA knockdown are combined to show that neuronal microRNA miR-138 targets ICP0, Oct-1 and Foxc1 to repress HSV-1 lytic cycle genes and promote epigenetic gene silencing, thereby favouring viral latency.

Cryo-electron microscopy structure of heterodimeric GABA_B receptor in complex with G_i1 protein reveals that the mode of G-protein binding in this class-C G-protein-coupled receptor differs from that of other classes.

Temporal multi-omic analysis of tissues from rats undergoing up to eight weeks of endurance exercise training reveals widespread shared, tissue-specific and sex-specific changes, including immune, metabolic, stress response and mitochondrial pathways.

Morphometric analyses of hominid teeth from Early to Middle Pleistocene Java reveal that Meganthropus was a Pleistocene Indonesian hominid distinct from Pongo, Gigantopithecus and Homo, and that molars previously assigned to Homo erectus are more likely to belong to Meganthropus.

CRISPR screen identifies coactivators of the androgen receptor (AR) complex, including NSD2. NSD2 contributes to AR cistrome reprogramming during prostate cancer progression, and its degradation via a novel PROTAC reduces prostate cancer cell viability in vitro.

Light-induced contraction in the out-of-plane direction in two-dimensional (2D) hybrid perovskites enables the realization of high-efficiency 2D perovskite solar cells.