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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.

Triacylglycerols are an energy source produced in humans by DGAT1 and DGAT2, but disrupting these enzymes reveals a noncanonical pathway involving the protein DIESL (formerly TMEM68) and its regulator TMX1, which is important during lipid scarcity.

Our understanding of the functional link between differential DNA methylation and type 2 diabetes and obesity remains limited. Here the authors present a blood-based EWAS of fasting glucose and insulin among 4808 non-diabetic Europeans and identify nine CpGs not previously implicated in glucose, insulin homeostasis and diabetes.

The so-called two-dimensional (2D) layered perovskites possess distinct optoelectronic properties from their 3D counterparts due to their reduced dimensionality. Here Seitz et al. investigate the exciton transport dynamics in 2D perovskites and highlight the impact of the stiffness of the lattice.

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.

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.

RNA-guided epigenome editing with Cas9 fused to an acetyltransferase domain activates gene expression through modification of promoters and enhancers.

Evidence for a past large explosive eruption within the Santorini caldera suggests that early stages of silicic caldera cycles can be more hazardous than previously assumed, according to analyses of intra-caldera deposits from the Kameni Volcano.

Tumour vasculature influences drug delivery. Here, the authors show that SOD3 re-expression enhances doxorubicin delivery and effects through normalization of tumour vasculature via the HIF-2a/VE-cadherin pathway.

Anthropogenic losses of animal pollinators threaten ecosystem functioning. Here the authors report a global analysis showing geographically varied yet widespread declines of pollinator diversity and abundance with land use intensification, particularly in tropical biomes.

The reprogramming of fibroblasts to pluripotent stem cells has been well documented but there is interest in identifying additional factors involved. Here, the authors perform a screen of human kinases and show that the bromodomain protein, BRD3R, can promote reprogramming and suggest a role for this factor in regulating mitosis.

ISG15 is a ubiquitin-like protein which has important immune-related functions in mice and humans. Here the authors demonstrate that, unlike in mice, human ISG15 stabilizes UPS18 and that ISG15-deficient human cells are more resistant to viral infection.

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.

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.

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.

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.

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.

A study mapping the tree species richness in Amazonian forests shows that soil type exerts a strong effect on species richness, probably caused by the areas of these forest types. Cumulative water deficit, tree density and temperature seasonality affect species richness at a regional scale.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

Leukocyte migration over two-dimensional surfaces is dependent on the integrin family of adhesion receptors, which couple the contractile force of the actomyosin cytoskeleton to the extracellular environment. In this study, all integrin heterodimers from mouse leukocytes were ablated and it is shown that integrins are not required for migration in 3D environments, in vitro and in vivo. Such non-adhesive migration renders leukocytes autonomous from the tissue environment.

The TGF-β signalling pathway promotes cancer progression in late stage breast cancer, but how the pathway is activated is not always clear. In this study, Zhou et al.identify that the expression of nuclear receptor NR4A1 is induced by inflammation and is an activator of TGF-β-induced metastasis.

The Somatic Mosaicism across Human Tissues Network aims to create a reference catalogue of somatic mosaicism across different tissues and cells within individuals.

The binding of small-molecule inhibitors of the RSV F glycoprotein in a central cavity in the prefusion conformation stabilizes this conformation and blocks the conformational changes required for fusion with host membranes.

The Bcr-Abl tyrosine kinases p210 and p190 are linked to different leukemias and differ by the Dbl homology (DH) and Pleckstrin-homology (PH) domains. Here the authors characterize structures of the Bcr-Abl p210 DH and PH domains and find that the PH domain is important for the cellular localization and signaling network of p210.

The time-varying effective reproductive number (Rt) is useful for monitoring transmission of infections such as COVID-19, but reporting delays impact case count-based estimation methods. Here, the authors demonstrate and validate a method for estimation of Rt based on viral load data from Hong Kong that does not require accurate daily counts.

Genome-wide association analyses of 41,917 bipolar disorder cases and 371,549 controls of European ancestry provide new insights into the etiology of this disorder and identify novel therapeutic leads and potential opportunities for drug repurposing.

Genome-wide association studies (GWAS) have become a key tool to discover genetic markers for complex traits; however, environmental factors that interact with genes are rarely considered. Here, the authors conduct a GWAS of obesity traits, and find that smoking may alter genetic susceptibilities.

Potential gains in future salmon habitat associated with glacier loss have yet to be quantified. This study projects future gains in Pacific salmon freshwater habitat within western North America by linking a model of glacier mass change for 315 glaciers, forced by five different Global Climate Models, with a simple model of salmon stream habitat potential.

In most human tumours, the cell cycle regulators Cdk4/6-cyclinD are overactive. Here the authors use C. elegansas a model system to identify downstream regulators that are critical in the response of tumour cells to Cdk4/6 inhibitors.

Immagini radar di Marte sembrano rivelare masse di acqua salata sotto la calotta glaciale del Polo Sud del pianeta.

Thlaspi arvense (pennycress) has the potential to provide new sources of food and bioproducts when grown as a winter cover crop. Here, Chopra et al. demonstrate that multiple desirable traits can be stacked to rapidly domesticate pennycress. The resulting crop integrates into current crop rotations and produces seeds with improved nutritional qualities, easier harvesting and suitability for human consumption.

IL1R1-signaling triggers enteric glia reactivity, resulting in enteric gliosis, macrophage activation and the development of postoperative ileus.

Geoffrey Woods, Jan Senderek and colleagues show that biallelic mutations in PRDM12 cause congenital insensitivity to pain. They further show that PRDM12 is expressed in nociceptors and their progenitors and participates in sensory neuron development in Xenopus.

The relationships between people can have important consequences for the systems they depend on. Here the authors show that when coral reef fishers face commons dilemmas, the formation of cooperative communication with competitors can lead to positive gains in reef fish biomass and functional richness.