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Observations from a borehole in the Kamb Ice Stream suggest that discrete subglacial discharge events dominate channel melt and sediment transport.

Metabolic enzymes of the tricarboxylic acid cycle, such as 2-oxoglutarate dehydrogenase, are differentially expressed in absorptive and secretory lineages, guiding cell fate establishment and offering insights for targeted regenerative therapies.

Modifications enhancing degradation resistance and albumin affinity enabled the delivery of an siRNA conjugate silencing MMP13 to guinea pig and murine arthritic joints, improving therapeutic outcomes following intravenous administration.

This paper highlights the far-red chemigenetic H₂O₂ reporter oROS-HT₆₃₅, which enables detailed insights into intricate intracellular and intercellular H₂O₂ dynamics, along with their environmental interactants, through spatially resolved, multiplexed real-time H₂O₂ imaging.

The paper describes a Genome in a Bottle benchmark for the X and Y chromosomes enabled by complete chromosome assemblies. This benchmark enables users to evaluate small variant accuracy in challenging repetitive regions of the sex chromosomes.

Jamaican fruit bats support disseminated infection of Ebola but not Marburg virus. The differences in infection dynamics are partially attributable to Marburg’s less efficient entry and impaired antagonism of type I interferon signaling.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Streptomyces bacteria produce metabolites with diverse biological activities. Here, Ho et al. show that some of these metabolites are volatile terpenes that attract fruit flies, while other metabolites can kill the insect’s larvae upon ingestion of bacterial spores.

A device architecture based on indium arsenide–aluminium heterostructures with a gate-defined superconducting nanowire allows single-shot interferometric measurement of fermion parity and demonstrates an assignment error probability of 1%.

A new elpistostegalian from the Late Devonian period has been discovered that shows disparity in the group and represents a previously hidden ecological expansion, a secondary return to open water, near the origin of limbed vertebrates.

In a large, partially prospective cohort of patients with molecularly profiled and clinically annotated meningioma, the extent of surgical resection and radiotherapy (RT) response correlate with molecular classification, which can be used in a molecular model to predict clinical outcomes in response to RT.

Two below-threshold surface code memories on superconducting processors markedly reduce logical error rates, achieving high efficiency and real-time decoding, indicating potential for practical large-scale fault-tolerant quantum algorithms.

Using newly derived genome sequences of 137 marine microbial isolates as well as previously obtained genome and metagenome data, this study presents a functional analysis of picoplankton residing in the ocean's surface layer.

Mitochondria are able to maintain two competing metabolic pathways—oxidative phosphorylation and the reductive synthesis of proline and ornithine—by generating two mitochondrial subpopulations that are enriched in either pyrroline-5-carboxylate synthase or ATP synthase.

Bacteroides fragilis toxin expression induces goblet cell and goblet-cell-associated passage development during the pre-weaning period in mice, enabling B. fragilis to access a privileged lamina propria niche and evade competition with gut lumen bacteria.

The goal of the 1000 Genomes Project is to provide in-depth information on variation in human genome sequences. In the pilot phase reported here, different strategies for genome-wide sequencing, using high-throughput sequencing platforms, were developed and compared. The resulting data set includes more than 95% of the currently accessible variants found in any individual, and can be used to inform association and functional studies.

Designed novel protein nanoparticle technology integrates antibody targeting and responds to changes in environmental conditions to release protected molecular cargoes, opening new applications for precision medicine.

Limited tumor cell delivery is a major challenge for the efficacious delivery of siRNAs to silence traditionally undruggable oncogenes. Here the authors optimize siRNAs for in situ binding to albumin through C18 lipid modifications and show the application of the lead conjugate structure for targeting MCL1 in orthotopic breast tumors in mice.

Dynamics of type I interferon (IFN) following infection with SARS-CoV-2 are critical in determining disease severity in humans but have been difficult to model in mice. Here, infection of genetically diverse mice reveals how delayed or immediate IFN signaling coordinates antiviral immunity.

Analyses of samples from patients with acute myeloid leukaemia reveal that drug response is associated with mutational status and gene expression; the generated dataset provides a basis for future clinical and functional studies of this disease.

The Omicron variant evades vaccine-induced neutralization but also fails to form syncytia, shows reduced replication in human lung cells and preferentially uses a TMPRSS2-independent cell entry pathway, which may contribute to enhanced replication in cells of the upper airway. Altered fusion and cell entry characteristics are linked to distinct regions of the Omicron spike protein.

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.

Primary open-angle glaucoma (POAG) is highly heritable, yet not well understood from a genetic perspective. Here, the authors perform a meta-analysis of genome-wide association studies in 34,179 POAG cases, identifying 44 previously unreported risk loci and mapping effects across multiple ethnicities.

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.

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.