Search

The Toxoplasma gondii effector TgROP1 mimics host factors to bind VAPA/B, thereby establishing parasite–host ER contact sites.

Electrochemical devices producing oxygen in space face limited buoyancy, hindering gas bubble removal and increasing reaction overpotentials. Now, it has been shown that commercial magnets can enhance the reaction efficiency and induce phase separation in microgravity. The optimized magnetoelectrochemical architectures developed here may guide the designs of future life-support systems.

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.

HCMV rearranges the host cell to produce infectious virus but molecular details are still unclear. Here, the authors analyze the transcriptome of infected cells and show that HCMV turns on dormant neuronal genes through chromatin manipulation to achieve this goal.

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).

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.

The velvet worm emits a rapidly oscillating jet of proteinaceous slime to capture prey. Here, Concha et al. combine high-speed videography and a physical simulacrum to establish that this passive mechanism is the result of elastohydrodynamic instability during high-speed flow through the oral papillae.

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.

Improving mass transfer through hierarchically porous synthetic materials is a great challenge. Here the authors address this by expanding the original Murray’s law, a biomimetic principle defining the branching of veins in living structures.

This study uncovered genetic associations with environmental sensitivity in psychiatric and neurodevelopmental traits in an international collaboration using data from more than 21,000 monozygotic twins—the largest genetic study of monozygotic twin differences to date.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

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.

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.

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.

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.

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.

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.

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.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

Electrocatalytic water splitting to produce H₂ is impeded by slow reaction kinetics over noble-metal-free catalysts at the electrodes. Here, the authors use high-frequency alternating magnetic fields to locally heat FeC–Ni core–shell catalysts, enhancing the kinetics of the oxygen and hydrogen evolution reactions.

It is currently challenging to mechanically assess 3D specimens without manual handling. Here the authors combine a micro-force sensor and an acoustically controlled manipulation device to enable rotation of samples while assessing mechanical properties at the chosen region.

Mitochondrial quality control mechanisms prevent damage accumulation, including in mitochondrial DNA (mtDNA). Here, Sen et al. show that altered mtDNA elicits local rearrangements in mitochondrial membrane potential and cristae structure, with mtDNA eliminated through VPS35 endosomes.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

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.

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.

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.

Molnupiravir is an antiviral that forces lethal error catastrophe in SARS-CoV-2 RNAs. Here, the authors confirm the mechanism of action of molnupiravir in humans using samples obtained from the UK’s AGILE phase IIa clinical trial investigating the antiviral efficacy of the drug against SARS-CoV-2. No treatment-associated SARS-CoV-2 mutations were identified.

Here the authors report the formation of toxic clumps of protein, similar to amyloid assemblies found in Alzheimer’s disease and suggest their possible role for some of the neurological symptoms of long-COVID.

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.

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.

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.

Breast cancer risk for BRCA1/BRCA2 mutation carriers varies depending on other genetic factors. Here, the authors perform a case-only genome-wide association study and highlight novel loci associated with breast cancer risk for BRCA1/BRCA2 mutation carriers.

COVID-19 can be associated with neurological complications. Here the authors show that markers of brain injury, but not immune markers, are elevated in the blood of patients with COVID-19 both early and months after SARS-CoV-2 infection, particularly in those with brain dysfunction or neurological diagnoses.

Migration of adult American eels from the coast to their spawning area in the Sargasso Sea have previously only been inferred from larval distributions. Here, Béguer-Pon et al. track adult eels from the continental shelf into the open ocean, with one individual migrating to the northern limit of the spawning site.

A randomized controlled trial showed that a home-based, telemedicine-supported lifestyle intervention, which consisted of exercise training, nutrition recommendations and health literacy training, reported improved glycemic control after 6 months in patients with coronary heart disease and type 2 diabetes compared to usual care.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

In this study, Aggarwal and colleagues perform prospective sequencing of SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge. They identify important factors that contributed to within university transmission and onward spread into the wider community.

Genome-wide association analyses of blood glucose measurements under nonstandardized conditions provide insights into the biology of glucose regulation, diabetes complications and pathways for treatment stratification.