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Recent technologies enable joint profiling of T cell RNA and T cell receptor (TCR) sequences at single-cell resolution. The authors here develop a TCR-RNA Integrating Model (TRIM) to predict intra tumor T cell signature post checkpoint inhibitor treatment by analyzing T cells from blood or tissues before treatment.

The Huayuan biota exhibits extraordinary biodiversity, illuminating the impact of the Phanerozoic mass extinction around 513 million years ago and offering critical insights into the transformation of global ecosystems in the early Cambrian.

Transcranial focused ultrasound can be used for neuromodulation, but its use in wearable systems remains challenging. The authors present a miniaturised wearable ultrasound device, integrated with a bioadhesive hydrogel for stable, long-term somatosensory cortical stimulation.

A nine-year transit-timing campaign has measured the extremely low masses and densities of four large planets orbiting the young star V1298 Tau, which are now predicted to contract and form a typical compact super-Earth and sub-Neptune system.

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.

How silicate weathering responds to and regulates Earth’s climate remain controversial. This study suggests the primary control of temperature on weathering intensity globally and the temperature-weathering feedback may be stronger in cold Earth.

This Perspective examines the development of thermal interface materials, exploring material and design strategies that balance thermal conductivity, mechanical compliance, thickness and electrical insulation, and proposes an integrated engineering framework for the future development of the materials.

The authors find cholinergic neurons regulate glymphatic waste clearance via neurovascular mechanisms, with their loss impairing this process. This finding suggests targets for diagnostics and treatment.

Single-cell profiling of human prostate cancer and studies in mouse models show that macrophages expressing SPP1 mediate immunotherapeutic resistance through adenosine pathway activation and represent a potential target for future studies.

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.

A new algorithm combined with ultrasound imaging allows for the quantification of kidney quality before transplantation, potentially helping to alleviate global demand for kidney transplantation.

Functional, tumour-promoting GABAergic neuron-to-glioma synapses in diffuse midline gliomas are identified.

How tree diversity effects on ecosystem functioning vary along climatic gradients is unclear. Here, analysing data from 15 experimental forest sites, the authors show that tree growth responses to neighbourhood species diversity are stronger in wetter climates but are unaffected by interannual climatic variation within sites.

Neurons in the central amygdala contribute to the reward prediction error responses of dopamine neurons to facilitate reward learning, but are not involved in aversive learning.

There is a need for accessible ways to improve peptide spectrum match rescoring with deep learning predictions in bottom-up proteomics. Here, the authors demonstrate robust gains in peptide/protein identifications across various experiments, from single cell proteomics to immunopeptidomics.

Low-intensity transcranial focused ultrasound (tFUS) is a non-invasive neuromodulation technique with high spatial specificity. The authors show that excitatory and inhibitory neurons respond differently to tFUS, suggesting the possibility of preferentially targeting specific neuron types via noninvasive tFUS.

Piezoresistors can be used in strain sensors for soft machines, but the traditional design process relies on intuition and human ingenuity alone. Haitao Yang and colleagues present a method built on genetic algorithms and other machine learning methods to design and fabricate strain sensors with improved capabilities.

The transcription factor FOXO1 has a key role in human T cell memory, and manipulating FOXO1 expression could provide a way to enhance CAR T cell therapies by increasing CAR T cell persistence and antitumour activity.

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.

Platelet aggregation is associated with myocardial infarction and stroke. Here, the authors have conducted a whole genome sequencing association study on platelet aggregation, discovering a locus in RGS18, where enhancer assays suggest an effect on activity of haematopoeitic lineage transcription factors.

Schizophrenia patients are impaired in attenuating responses to self-generated sensory input. Here, the authors reveal the same sensory deficit and reduced corollary discharge signaling in mice carrying a major genetic risk factor for schizophrenia.

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.

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.

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 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.

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.

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.

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.

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.

In a mouse tumour model, immunotherapy-induced rejection of tumour cells requires presentation of both MHC class I and MHC class II antigens, which activate CD4⁺ and CD8⁺ T cells, respectively.

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.

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.

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.

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.

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.

Chimeric antigen receptor T cell efficacy is enhanced with an interleukin 2-recruiting molecule.

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.

Integrated analysis of bacterial, fungal and microbial communities in the airways of patients with bronchiectasis demonstrates that interaction networks, rather than the relative abundance of any single microbial species, are associated with exacerbation risk.

Infusion of CD19-directed chimeric antigen receptor T cells into two patients with chronic lymphocytic leukaemia resulted in complete tumour remission and persistence of the infused cells more than ten years later.

This analysis presents the results of a community-based evaluation of existing software for large-scale glycopeptide data analysis.

The relationship of mycorrhizal associations with latitudinal gradients in tree beta-diversity is unexplored. Using a global dataset approach, this study examines how trees with arbuscular mycorrhizal and ectomycorrhizal associations contribute to latitudinal beta-diversity patterns and the environmental controls of these patterns.

Using the unique valley properties of a twisted MoTe₂ bilayer, measurements of the degree of circular polarization of trion photoluminescence reveal optical signatures of a zero-field composite Fermi liquid.