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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.

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.

Treatment with the oncolytic herpes virus CAN-3110 is associated with improved survival responses in patients with recurrent glioblastoma, particularly in individuals who are seropositive for HSV1.

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.

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.

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.

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.

A distinct population of CD4 T cells resides in specific regions of the steady-state brain, and these T cells are programmed in the periphery by the microbiome to coordinate adaptive behaviour.

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.

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.

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.

A reinforcement learning-based virtual reality system, implementing a series of sport sessions with coaching, was as effective as standard physical activity in reducing fat mass in adolescents, with positive effects on cognition.

Understanding the emergence, evolution, and transmission of antibiotic resistance genes (ARGs) is essential to combat antimicrobial resistance. Here, Munk et al. analyse ARGs in hundreds of sewage samples from 101 countries and describe regional patterns, diverse genetic environments of common ARGs, and ARG-specific transmission patterns.

Immune response during breast cancer progression remains to be explored. Here, the characterisation of sequential and parallel multiregion samples of an index patient and a cohort of metastatic triple-negative breast cancers reveals convergent immune evasion mechanisms and an increase in tumor genomic heterogeneity.

Xenovulene A is a fungal compound that has the potential to be used as an antidepressant. Here, the authors unravel the pathway leading to its formation in fungi and discover a new class of enzymes, which accounts for some unusual chemistry in the synthesis of xenovulene.

Here, Wang et al. use metagenomic sequencing to explore the impact of antibiotic treatment for Helicobacter pylori on the gut virome community in infected patients, showing that recurrent treatment leads to a lower virus community diversity and altered virus-bacteria interactions, compared with treatment naive patients.

Although immune checkpoint blockade is a standard treatment for patients with malignant mesothelioma, only a minority of patients exhibit radiological response. In a phase II clinical trial (MIST4) investigating the efficacy, safety and molecular correlates of response following treatment with atezolizumab and bevacizumab, the authors demonstrate that the gut microbiota may modulate responsiveness to treatment.

By comparing data from real-world grassland communities with data from two of the longest-running grassland biodiversity–ecosystem functioning experiments, the authors show that conclusions derived from experimental systems are robust to the removal of unrealistic experimental communities.

RAG2-SCID is a primary immunodeficiency caused by mutations in Recombination-activating gene 2 (RAG2). Here the authors report a RAG2 correction strategy that replaces the entire endogenous coding sequence (CDS) to maintain the endogenous spatiotemporal gene regulation and locus architecture.

Food biodiversity is likely to benefit both human health and agrifood systems. To assess food biodiversity, this epidemiological study proposes the use of dietary species richness, which is highly heterogeneous—both between and within countries—and is associated with lower rates of mortality in Europe and similar levels of micronutrient adequacy in low- and middle-income countries, as opposed to other classical indices.

Here, the authors develop the Gut Microbiome Wellness Index 2 (GMWI2), an enhanced version of the original GMWI prototype, designed as a disease-agnostic health status indicator based on gut microbiome taxonomic profiles.

A wireless device for measuring bioimpedance during breastfeeding allows accurate quantification of the volume of expressed milk in 12 new mothers in a neonatal intensive care unit and in home settings.

Positive relationships between biodiversity and temporal stability through species asynchrony are well-documented, but the underlying mechanisms remain debated. Here, the authors show that statistical averaging is the main mechanism of plant diversity effects on community stability.

Recovery of damaged ecosystems can vary in time and extent. Here, Moreno-Mateos and colleagues perform a meta-analysis to describe and quantify what they call recovery debt, an interim reduction in biodiversity, populations, and biogeochemical function of ecosystems during the recovery process.

A disturbed microbial network characterizes relapsing refractory Crohn’s disease and antedates disease recurrence after surgical removal of the active disease segment.

Economies dependent on natural resources could gain resilience to abrupt ecosystem and market shifts through proactive risk-buffering approaches. Using data from Alaskan fisheries, Clineet al. show that communities relying on diverse fisheries were more resilient to major ocean and market regime shifts in 1989.

In this Consensus Statement, the authors describe the details of the evolution of the risk-based treatment of favourable-histology Wilms tumour (FHWT) and outline the rationale for the new risk stratification that will be used in the now open Children’s Oncology Group therapeutic trial for FHWT, AREN2231.

By analysing the genome of over 9,000 pig-associated isolates, this study shows that modernized agricultural systems have favoured the acquisition of antimicrobial resistance genes, population expansion and global transmission of pig-enriched Salmonella over the past century.

Cryo-electron microscopy analysis of the extracellular flagellum structure, including the hook–filament junction and filament cap complex, reveals mechanisms of flagellin incorporation into the growing filament and filament stabilization.

In this genomic analysis of peripheral blood samples of the phase 3 CheckMate-067 trial of ipilimumab (IPI) versus nivolumab (NIVO) versus ipilimumab and nivolumab (IPI-NIVO) in melanoma, the status of certain mitochondrial haplogroups in patients was associated therapeutic resistance to NIVO or IPI-NIVO, a finding validated in an independent cohort.

Yogurt consumption is associated with health benefits, but underlying mechanisms are unknown. Here, the authors show in a mouse model that yogurt intake prevents obesity-linked insulin resistance and hepatic steatosis through shifting the gut microbiota and enhancing production of fermentation-derived branched chain hydroxy acids.

Survival during fasting requires release of adipose tissue lipid stores and is thought to be dependent on canonical lipases, including the rate limiting action of adipose triglyceride lipase. Here the authors show that lysosomes and lysosomal acid lipase play a critical role in adipocyte lipolysis with fasting in mice.

Multi-omics datasets are integrated to generate a unified and clinically informed molecular classification of meningiomas.

A study reports single-cell RNA-sequencing profiles for more than 1.6 million cell nuclei from 101 whole mouse embryos including 22 mutant and 4 wild-type genotypes, from one experiment.

The global biodiversity decline might conceal complex local and group-specific trends. Here the authors report a quantitative synthesis of longterm biodiversity trends across Europe, showing how, despite overall increase in biodiversity metric and stability in abundance, trends differ between regions, ecosystem types, and taxa.

Productive influenza infection can be improved by cooperation and this varies between viral strains and hosts. By quantifying the rates of reassortment and virus production using several methods, including single-cell sequencing, the authors find that isolates of the avian H9N2 influenza subtype are dependent on infections with a second virus, but only in mammalian cells and not in avian cells. These findings are supported by in vivo experiments in guinea pigs and quail. The authors find indications that this type of cooperation between influenza A viruses depends on the RNA polymerase subunit PA.

NOD-like receptor family pyrin domain-containing 6 (NLRP6) reduces colitis severity in a gut microbiome-dependent manner; however, in the context of murine intestinal graft-versus-host disease, NLRP6 exacerbates symptoms independently of gut microbiome composition and diversity, with NLRP6-deficient animals displaying protection against disease.

DNA methylation (DNAm) is a key biomarker of aging, with age-related DNAm changes being well-characterized. Here, the authors show that low-methylated regions (LMRs) bound by PRC2 in embryonic stem cells gain methylation with age in somatic cells, proposing the “PRC2-AgeIndex” as a universal biomarker of cellular aging.

Mouse models of lung and colorectal cancer with sporadic DNA mismatch repair deficiency clarify that the intratumor heterogeneity and clonal architecture rather than tumor mutational burden are powerful determinants of immunotherapy response.

A consensus cell type atlas for the fly brain provides both an intellectual framework and open-source toolchains for brain-scale comparative connectomics.