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Integrating tissue histology with spatial transcriptomics (ST) can significantly enhance the analysis of tumor heterogeneity and the tumor microenvironment (TME). Here, the authors present METI, a computational framework to analyze cancer cells and the complex TME by integrating ST with histology imaging.

Pancreatic ductal adenocarcinoma (PDAC) cells can utilise the tumour microenvironment to metastasise to the liver. Here the authors show that hepatoctyes overexpress SLIT2 to enable premetastatic niche formation for ROBO1-positive PDAC cells to support the survival of these tumour cells in the liver.

Tetrahedral DNA framework-enabled bulk enzyme heterojunctions have been used to program biosensor interfaces. Here, the authors use DNA tetrahedrons to tether enzymes of an enzymatic cascade to gold electrodes, hence raising them over the bulk solution, which led to improved kinetics and sensitivity.

Type 2 diabetes is associated with islet amyloid deposits derived from islet amyloid polypeptide (IAPP) expressed by β-cells. Here the authors show that IAPP misfolded protein stress induces the hypoxia inducible factor 1 alpha injury repair pathway and activates survival metabolic changes mediated by PFKFB3.

Through combining nanochannel technique and host–guest interaction, a universal tuneable nanofluidic diode is fabricated. By changing different azobenzene derivatives, the system can achieve replaceable surface charges, and realize the light and pH dual stimuli responses. The system has potential applications in fields such as photosensitive nanofluidic devices, light-controlled drug transport, pH-activated drug release and devices for optical information storage.

Beta-arrestin-2, an adaptor protein, is necessary for efficient insulin signalling by scaffolding downstream kinases, Akt and Src, to the insulin receptor. Without beta-arrestin-2 insulin resistance develops.

Current preclinical imaging of intestine in animal models cannot reveal intestinal dynamics in awake condition. Here the authors report a Transillumination Intestine Projection (TIP) imaging system for free-moving mice, and showed the intestine dynamics in conscious animal in natural physiological states.

Microsatellite instability (MSI), caused by deficiency of the DNA mismatch repair system, has been associated with improved response to immune checkpoint blockade (ICB). Here the authors show that inactivation of protein phosphatase 2A induces a MSI status, promoting cytotoxic T cell infiltration and response to ICB in pre-clinical cancer models.

RNA splicing is crucial for gene expression diversity and can be altered by mutations. Here, the authors present SpTransformer, a deep learning tool that predicts tissue-specific RNA splicing with high accuracy, revealing splicing’s role in pathogenic mutations and aiding clinical interpretations.

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.

Entanglement distillation is essential for quantum information applications, generating remote entanglement in repeater units. Here, a filtering protocol using two-qubit entangled states in an atomic ensemble is proposed and demonstrated in a proof-of-principle experiment.

Cells maintain a constant cytoplasm to nucleus volume ratio, although the role of DNA damage is not well explored. Here, the authors use Drosophila to connect TER94, the fly homolog of VCP, to disruption of DNA damage repair, leading to ubiquitinated Mu2 protein accumulation and enlarged nuclei.

Neurogenesis is an ordered transition from pluriptotent cells to neural precursor cells (NPCs) to neurons. Here the authors show that loss of the lysine demethylases JMJD3 and UTX leads reduced DNA accessibility at neurogenesis loci in human NPCs, and that the chromatin remodeller BAF can rescue differentiation defects.

Here, the authors show that the interatomic coupling between two layers of a 2D crystal can be determined by studying the angle-resolved photoemission spectra of a trilayer structure with one aligned and one twisted interface, and obtain the inter-atomic coupling for carbon atoms in twisted trilayer graphene.

Full-fledged quantum communication networks would allow distributed quantum computing across multiple remote nodes, but typical implementations are stuck at meters-scale distances. Here the authors demonstrate teleportation-based nonlocal CNOT gates, distributed Deutsch-Jozsa algorithm and quantum phase estimation across 7 km space separation.

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.

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.

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.

Whether Rft1 plays a role during M5GN2-PP-Dol translocation has been controversial for over two decades. In this work, a reconstituted in vitro assay demonstrates that purified Rft1 is sufficient to flip M5GN2-PP-Dol across the lipid bilayer.

This paper reports integrative molecular analyses of urothelial bladder carcinoma at the DNA, RNA, and protein levels performed as part of The Cancer Genome Atlas project; recurrent mutations were found in 32 genes, including those involved in cell-cycle regulation, chromatin regulation and kinase signalling pathways; chromatin regulatory genes were more frequently mutated in urothelial carcinoma than in any other common cancer studied so far.

Product toxicity is one of the factors that hinder biofuel production. Here, the authors engineer the actin cytoskeleton to increase cell growth and production of n-butanol and medium-chain fatty acids in Saccharomyces cerevisiae.

The authors show that captive populations of zebra finches, which have been kept in isolation for up to 100 generations, have diverged in song dialect. When individuals singing different dialects are mixed, mating is assortative for song dialect.

Ahmed, Nguyen et al. show that two FDA-approved antibiotics, paromomycin and neomycin, promote cardiomyocyte proliferation and improve cardiac function after myocardial infarction in mice and pigs by interfering with the cell division inhibiting function of transcription factors Meis1 and Hoxb13.

Demonstrations of sensing devices using nitrogen vacancy centres have shown significantly improved sensitivity compared to traditional methods. Here the authors demonstrate an approach for performing nanoscale electron spin resonance without magnetic fields in order to achieve better spectral resolution.

In a recent clinical trial for oral administration of cipargamin in individuals with malaria, there was an emergence of recrudescent parasites with a G358S mutation in PfATP4. In this work, the authors investigate the effect of this mutation on the function of the ATPase, on parasite growth and susceptibility to antimalarial drugs.

Size matching molecular design utilizing host-guest chemistry is a general and promising strategy for seeking new functional materials. Here the authors screen different sized nitrogen rich azoles for selective encapsulation into a hydroxylammonium framework to achieve a dense packing and higher energetic performance.

Chen et al. report that TGF-β signalling, although largely considered anti-inflammatory, has proinflammatory effects on endothelial cells. Inhibition of endothelial TGF-β signalling decreases atherosclerosis in mice and reverts established plaques, in part by decreasing endothelial-to-mesenchymal transitions.

Dynamic assembly and disassembly of primary cilia is critical for tissue development and homeostasis. Here the authors identify lysophosphatidic acid (LPA) as a physiological extracellular factor that initiates cilia disassembly through both YAP/TAZ mediated transcription and calcium/calmodulin mediated activation of Aurora A.

The intrinsic high-concentration Ge vacancies in GeTe-based thermoelectric materials hinder their performance maximization. Here, the authors find that defect structure engineering strategy is effective for performance enhancement.

Here the authors show disturbing parental histone inheritance in cancer cells drives tumor progression by reprogramming the epigenetic profile and conferring fitness advantages to some of the newly emerged subclones.