Search

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.

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.

Neurodegenerative disorders remain poorly treated despite their growing disease burden. Here, authors developed a multiplexed screening platform that identified DNAJB6 as a modulator of condensate maturation and suppressor ALS/FTD-linked toxicity.

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.

Here, using a genome-wide CRISPR screen, Bitew et al. identify GRA38, a phosphatidic acid phosphatase, as a key factor in Toxoplasma gondii adaptation to lipid-rich conditions via keeping lipid balance, sustaining growth, ultimately ensuring survival.

NMR spectroscopy and imaging show that dendrites in a solid-state Li battery are formed from Li plating on the electrode and Li⁺ reduction at solid electrolyte grain boundaries, with an interlapped stalled growth period.

The authors performed phylogenetically controlled behavioural assays and analysed brain transcriptomes across five avian families, identifying convergent patterns of gene expression associated with aggression and nesting behaviour in obligate cavity-nesting birds.

Human host-associated cellular products may act as induction agents for bacteriophages.

The INTIMET study is a randomized 26-week double-blind clinical trial to assess whether metformin can reduce insulin resistance in adults with type 1 diabetes. Metformin did not reduce insulin resistance in type 1 diabetes, but lowered insulin dose versus placebo – a secondary outcome.

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).

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.

Researchers use adaptive optics to correct distortions from digital micromirror devices in Hadamard single-pixel microscopy. The sensorless method restores sharp detail, nears diffraction-limited resolution, while correcting sample-induced aberrations.

A new version of nanorate DNA sequencing, with an error rate lower than five errors per billion base pairs and compatible with whole-exome and targeted capture, enables epidemiological-scale studies of somatic mutation and selection and the generation of high-resolution selection maps across coding and non-coding sites for many genes.

Withanolides are plant steroids with potent bioactivities found in many medicinal plants including Withania somnifera, but their biosynthetic pathway is largely unknown. Here, the authors report the genome assembly of W. somnifera and reveal a conserved gene cluster in Solanaceae plants for withanolide biosynthesis.

The way in which the brain processes language from a collection of sounds to meaningful concepts remains poorly understood. Here, the authors show that the brain’s temporal responses to speech closely follow the layer-by-layer progression of LLMs, revealing shared computational principles.

Imaging crystal structure and orientation in operando conditions inside real batteries is crucial but rare. Here, authors demonstrate the power of operando 2D X-ray imaging to understand complex Li extraction and deposition mechanisms in solid state batteries.

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.

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.

Drosophila RNAi libraries are commonly used to perform large-scale functional genetics screens in vivo. Here the authors find that a subset of lines from the VDRC KK RNAi line cause false-positive enhancement of the Hippo pathway, and provide a strain that can test whether a genetic screen of interest will be affected by this technical artefact.

Induced proximity by molecular glues is a strategy that leverages the recruitment of proteins to facilitate their modification or degradation. Here the authors present unbiased quantitative proteomic, biochemical and computational workflows that uncover hundreds of CRBN molecular glue targets using recombinant protein and cell lysate.

Claudin 18.2 (CLDN18.2) has emerged as a target for gastrointestinal cancer, however, on-target/off-tumor toxicities have been also reported. Here, after reporting evidence of erosive gastritis in patients treated with CLDN18.2 targeted immunotherapies, the authors develop and characterize CLDN18.2 fully-human VH-only single domain CARs, showing that a lower affinity CAR mitigates on-target/off-tumor toxicity while preserving anti-tumor efficacy in gastric cancer models.

A high-resolution antigenic map of influenza A(H5) haemagglutinin (HA) enables the design of immunogenic and antigenically central vaccine HA antigens that elicit antibody responses broadly covering the A(H5) antigenic space.

High-depth sequencing of non-cancerous tissue from patients with metastatic cancer reveals single-base mutational signatures of alcohol, smoking and cancer treatments, and reveals how exogenous factors, including cancer therapies, affect somatic cell evolution.

Temporal interference stimulation is thought to act via low-frequency envelope demodulation. Here, the authors demonstrate that stimulation thresholds in TIS follow the same carrier frequency dependence as direct kHz stimulation, indicating a shared biophysical mechanism.

Fiber-reinforced polymer composites are lightweight structural materials used in a wide range of applications, but manufacturing of composites requires expensive tooling and long, energy-intensive processing. Here, the authors report rapid, scalable, and energy-efficient additive manufacturing of fiber-reinforced thermoset composites, while eliminating the need for tooling or support materials.

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.

A free-living trial in people with overweight or obesity found that minimally processed diets led to greater weight loss and cardiometabolic improvements than ultraprocessed diets following UK healthy eating guidelines at 8 weeks.

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.

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.

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.

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.

CRISPR-associated transposases represent a promising tool for precise, DSB-free genome editing. Here, authors investigate a CAST system active in human cells, improve activity via structure-guided engineering, and develop novel chimeras for improved modularity.

Illness signals from the gut reactivate and strengthen flavour representations in the amygdala to support learning from delayed postingestive feedback.

A unified framework is presented that integrates observed spatial patterns of individual trees in forests with ecological processes into a novel coexistence theory.

Using mathematical modeling of RSV and hMPV, this study found lowered transmissibility of hMPV and suppressive effects on hMPV transmission. Peak timing and magnitude of hMPV may shift due to RSV interventions, but the overall burden is small.

Gas adsorption in porous materials offers an alternative technology for efficient hydrogen isotope separation. Here, the authors report high separation efficiency through isotopologue-induced structural dynamics in a readily scalable manganese-triazole metal-organic framework.

Phase-sensitive amplifiers are known for low-noise amplification and nonlinearity mitigation, but their long-haul implementation is challenging. The authors use these amplifiers to show a long-haul optical link with a 5.6-times reach improvement over conventional amplifier performance, affirming their viability as an alternative technology.

Geological evidence from the North Qilian paleo-subduction channel shows that strong blocks deform by dislocation creep, sustain >100 MPa stresses, and their interactions transiently tighten plate coupling, shedding light on deep slow-slip dynamics.

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.

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.

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.

Conserving and restoring ecosystems requires understanding what natural vegetation would look like without human disturbance. This study maps the most likely global cover of trees, short vegetation, and bare ground, showing that land management through fire and herbivory may influence ecosystems more than climate change alone.

This study found E. coli phylogenetic background shapes TEM-1 beta-lactamase expression and co-amoxiclav resistance. Phylogeny alone shifted isolates from susceptible to resistant, stressing a need for lineage-sensitive genotype-phenotype prediction.

GTPase-activating proteins (GAPs) often contain regulatory PH domains. In this work, Soubias et al, using an integrated structure-function approach, discovered a mechanism where a GAP PH domain binds directly to a GTPase to induce allosteric changes facilitating GTP hydrolysis.